10-K

UNITED STATES SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

Form 10-K

☑ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the fiscal year ended December 31, 2023

OR

☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the transition period from to

Commission File No. 001-36276

Ultragenyx Pharmaceutical Inc.

(Exact name of registrant as specified in its charter)

Delaware	27-2546083
(State or other jurisdiction of incorporation or organization)	(I.R.S. Employer Identification No.)
60 Leveroni Court Novato, California	94949
(Address of principal executive offices)	(Zip Code)

(415) 483-8800

(Registrant’s telephone number, including area code)

Securities registered pursuant to Section 12(b) of the Exchange Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, $0.001 par value	RARE	The Nasdaq Global Select Market

Securities registered pursuant to Section 12(g) of the Exchange Act: None.

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☑ NO ☐

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Exchange Act. YES ☐ No ☑

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Exchange Act during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☑ NO ☐

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ☑ NO ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

Large accelerated filer ☑ Accelerated filer ☐ Non- accelerated filer ☐ Smaller reporting company ☐ Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☑

If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐

Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). YES ☐ NO ☑

The aggregate market value of the voting and non-voting common equity held by non-affiliates of the Company as of June 30, 2023 was approximately $3.1 billion, based upon the closing price on The Nasdaq Global Select Market reported for such date. Shares of common stock held by each executive officer and director and by each person who is known to own 10% or more of the outstanding common stock have been excluded as such persons may be deemed affiliates of the Company. This determination of affiliate status is not necessarily a conclusive determination for other purposes.

As of February 15, 2024, the Company had 82,335,687 shares of common stock issued and outstanding.

DOCUMENTS INCORPORATED BY REFERENCE

Portions of the registrant’s definitive proxy statement relating to its 2024 Annual Meeting of Stockholders, to be held on or about June 18, 2024, are incorporated by reference into Part III of this Annual Report on Form 10-K where indicated. Such proxy statement will be filed with the U.S. Securities and Exchange Commission within 120 days after the end of the fiscal year to which this report relates.

Table of Contents

		Page
	PART I
Item 1.	Business	4
Item 1A.	Risk Factors	30
Item 1B.	Unresolved Staff Comments	66
Item 1C.	Cybersecurity	66
Item 2.	Properties	66
Item 3.	Legal Proceedings	67
Item 4.	Mine Safety Disclosures	67
	PART II
Item 5.	Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities	68
Item 6.	Reserved	68
Item 7.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	69
Item 7A.	Quantitative and Qualitative Disclosures About Market Risk	79
Item 8.	Financial Statements and Supplementary Data	80
Item 9.	Changes in and Disagreements With Accountants on Accounting and Financial Disclosure	80
Item 9A.	Controls and Procedures	80
Item 9B.	Other Information	81
Item 9C.	Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	81
	PART III
Item 10.	Directors, Executive Officers and Corporate Governance	82
Item 11.	Executive Compensation	82
Item 12.	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	82
Item 13.	Certain Relationships and Related Transactions, and Director Independence	82
Item 14.	Principal Accountant Fees and Services	82
	PART IV
Item 15.	Exhibits and Financial Statement Schedules	83
Item 16.	Form 10-K Summary	88
SIGNATURES		89

CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

This Annual Report on Form 10-K, or Annual Report, contains forward-looking statements that involve risks and uncertainties. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. All statements other than statements of historical fact contained in this Annual Report are forward-looking statements. In some cases, you can identify forward-looking statements by words such as “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “seek,” “should,” “target,” “will,” “would,” or the negative of these words, or other comparable terminology. These forward-looking statements include, but are not limited to, statements about:

•our commercialization, marketing, and manufacturing capabilities and strategy;

•our expectations regarding the timing of clinical study commencements and reporting results from same;

•the timing and likelihood of regulatory approvals for our product candidates;

•the anticipated indications for our product candidates, if approved;

•the potential market opportunities for commercializing our products and product candidates;

•our expectations regarding the potential market size and the size of the patient populations for our products and product candidates, if approved for commercial use;

•estimates of our expenses, revenue, capital requirements, and our needs for additional financing;

•our ability to develop, acquire, and advance product candidates into, and successfully complete, clinical studies;

•the implementation of our business model and strategic plans for our business, products and product candidates and the integration and performance of any businesses we have acquired or may acquire;

•the initiation, timing, progress, and results of ongoing and future preclinical and clinical studies, and our research and development programs;

•the scope of protection we are able to establish and maintain for intellectual property rights covering our products and product candidates;

•our ability to maintain and establish collaborations or strategic relationships or obtain additional funding;

•our ability to maintain and establish relationships with third parties, such as contract research organizations, contract manufacturing organizations, suppliers, and distributors;

•our financial performance and the expansion of our organization;

•our ability to obtain supply of our products and product candidates;

•the scalability and commercial viability of our manufacturing methods and processes;

•developments and projections relating to our competitors and our industry;

•stagnating or worsening business and economic conditions and increasing geopolitical instability, including inflationary pressures, general economic slowdown or a recession, high interest rates, foreign exchange rate volatility, financial institution instability, a potential government shutdown, and changes in monetary policy;

•the impact of market conditions and volatility on unrealized gains or losses on our nonqualified deferred compensation plan investments and our financial results; and

•other risks and uncertainties, including those listed under “Part I, Item 1A. Risk Factors.”

Any forward-looking statements in this Annual Report reflect our current views with respect to future events or to our future financial performance and involve known and unknown risks, uncertainties, and other factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by these forward-looking statements. Factors that may cause actual results to differ materially from current expectations include, among other things, those discussed under Part I, Item 1A. Risk Factors and elsewhere in this Annual Report. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Except as required by law, we assume no obligation to update or revise these forward-looking statements for any reason, even if new information becomes available in the future.

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This Annual Report also contains estimates, projections, and other information concerning our industry, our business, and the markets for certain diseases, including data regarding the estimated size of those markets, and the incidence and prevalence of certain medical conditions. Information that is based on estimates, forecasts, projections, market research, or similar methodologies is inherently subject to uncertainties and actual events or circumstances may differ materially from events and circumstances reflected in this information. Unless otherwise expressly stated, we obtained such industry, business, market, and other data from reports, research surveys, studies, and similar data prepared by market research firms and other third parties, industry, medical and general publications, government data, and similar sources.

As used in this Annual Report, “Ultragenyx,” “we,” “our,” and similar terms refer to Ultragenyx Pharmaceutical Inc. and its subsidiaries, unless the context indicates otherwise.

PART I

Item 1. Business

Overview

We are a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultrarare genetic diseases. We have built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease.

We were founded in April 2010 by our President and Chief Executive Officer, Emil Kakkis, M.D., Ph.D., and are led by a management team experienced in the development and commercialization of rare disease therapeutics. Our strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.

Our Strategy

The critical components of our business strategy include the following:

•Focus on rare and ultrarare genetic diseases with significant unmet medical need and clear biology. There are numerous rare and ultrarare genetic diseases that currently have no drug therapy approved that treat the underlying disease. Patients suffering from these diseases often have a significant morbidity and/or mortality. We focus on developing and commercializing therapies for multiple such indications with the utmost urgency. We also focus on diseases that have biology that is well understood. We believe that developing drugs that directly impact known disease pathways will increase the probability of success of our development programs. Our modalities of biologics, small molecules, adeno-associated virus, or AAV, gene therapy, and nucleic acids provide us with what we believe is an optimal set of options to treat genetic diseases by selecting the best treatment strategy available for each disease.

•In-license promising product candidates; retain global commercialization rights to product candidates. Our current product candidates are generally in-licensed from academic institutions or derived from partnerships with other pharmaceutical companies. We believe parties agree to license product candidates to us because they are confident in our team’s expertise in rare disease drug development and commercialization. We generally intend to retain global commercialization rights to our products and product candidates whenever possible to maximize the potential value of our product portfolio.

•Focus on excellent, rapid, and efficient clinical and regulatory execution on multiple programs in parallel. We believe that building a successful and sustainable rare disease-focused company requires very specific expertise in the areas of patient identification, clinical study design and conduct, and regulatory strategy. Because rare disease programs involve fewer patients and may have accelerated paths to market, we are able to feasibly develop multiple clinical-stage product candidates in parallel, resulting in a more diversified portfolio that provides multiple opportunities to create value, with some economies of scale.

•Commercialize through patient-focused global organization. We seek to commercialize our products throughout the developed world, in North America, the European Union, or the EU, the United Kingdom, or the U.K., Latin America, Turkey, Asia, and select international markets. We have established our own commercial organization in these markets and a network of third-party distributors in smaller markets. We believe our commercial organization is highly specialized and focused, due to the nature of rare disease treatment.

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Approved Products and Clinical Product Candidates

Our current approved therapies and clinical-stage pipeline consist of four product categories: biologics, small molecules, AAV gene therapy, and nucleic acid product candidates.

We have four commercially approved products, Crysvita® (burosumab) for the treatment of X-linked hypophosphatemia, or XLH, and tumor-induced osteomalacia, or TIO, Mepsevii® (vestronidase alfa) for the treatment of mucopolysaccharidosis VII, or MPSVII or Sly Syndrome, Dojolvi® (triheptanoin) for the treatment of long-chain fatty acid oxidation disorders, or LC-FAOD, and Evkeeza® (evinacumab) for the treatment of homozygous familial hypercholesterolemia, or HoFH. The following table summarizes our approved products and pipeline of clinical product candidates:

 

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Approved Products

Crysvita for the treatment of XLH and TIO

Crysvita is a fully human monoclonal antibody administered via subcutaneous injection, that targets fibroblast growth factor 23, or FGF23, developed for the treatment of XLH. XLH is a rare, hereditary, progressive, and lifelong musculoskeletal disorder characterized by renal phosphate wasting caused by excess FGF23 production. There are approximately 48,000 patients with XLH in the developed world, including approximately 36,000 adults and 12,000 children. Crysvita is the only approved treatment that addresses the underlying cause of XLH. Crysvita is approved in the U.S., the EU and certain other regions for the treatment of XLH in adult and pediatric patients one year of age and older.

Crysvita is also approved in the U.S. and certain other regions for the treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia, or TIO, associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older. There are approximately 2,000 to 4,000 patients with TIO in the developed world. TIO can lead to severe hypophosphatemia, osteomalacia, fractures, fatigue, bone and muscle pain, and muscle weakness.

We are collaborating with Kyowa Kirin Co., Ltd., or KKC, and Kyowa Kirin, a wholly owned subsidiary of KKC, on the development and commercialization of Crysvita globally.

Please see “—License and Collaboration Agreements—Approved Products— Kyowa Kirin Co., Ltd.” for a description of our collaboration and license agreement with KKC.

Mepsevii for the treatment of MPS VII

Mepsevii is an enzyme replacement therapy administered intravenously, or IV, that replaces the missing enzyme (beta-glucuronidase), developed for the treatment of Mucopolysaccharidosis VII, also known as MPS VII or Sly syndrome. MPS VII is a rare lysosomal storage disease that often leads to multi-organ dysfunction, pervasive skeletal disease, and death. MPS VII and is one of the rarest MPS disorders, affecting an estimated 200 patients in the developed world. Mepsevii is approved in the U.S., the EU and certain other regions for the treatment of children and adults with MPS VII.

Please see “—License and Collaboration Agreements—Approved Products—Saint Louis University” for a description of our license agreement with Saint Louis University.

Dojolvi for the treatment of LC-FAOD

Dojolvi is a highly purified, synthetic, 7-carbon fatty acid triglyceride administered orally, designed to provide medium-chain, odd-carbon fatty acids as an energy source and metabolite replacement, developed for people with long-chain fatty acid oxidation disorders, or LC-FAOD. LC-FAOD represents a set of rare metabolic diseases that prevents the conversion of fat into energy and can cause low blood sugar, muscle rupture, and heart and liver disease. Dojolvi is approved in the U.S. and certain other regions as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed LC-FAOD. There are approximately 8,000 to 14,000 patients in the developed world with LC-FAOD.

Please see “—License and Collaboration Agreements—Approved Products—Baylor Research Institute” for a description of our license agreement with Baylor Research Institute.

Evkeeza for the treatment of HoFH

Evkeeza is a fully human monoclonal antibody administered by IV, that binds to and blocks the function of angiopoietin-like 3, or ANGPTL3, a protein that plays a key role in lipid metabolism, developed for the treatment of homozygous familial hypercholesterolemia, or HoFH, a rare inherited condition. HoFH occurs when two copies of the familial hypercholesterolemia, or FH-causing genes are inherited, one from each parent, resulting in dangerously high levels (>400 mg/dL) of LDL-C, or bad cholesterol. Patients with HoFH are at risk for premature atherosclerotic disease and cardiac events as early as their teenage years. Evkeeza is approved in the U.S., where it is marketed by our partner Regeneron Pharmaceuticals, or Regeneron. It is also approved in the European Economic Area, or EEA, as a first-in-class therapy for use together with diet and other low-density lipoprotein-cholesterol, or LDL-C, lowering therapies to treat adults and adolescents aged five years and older with clinical HoFH. There are approximately 3,000 to 5,000 patients with HoFH in the developed world outside of the U.S.

Please see “—License and Collaboration Agreements—Approved Products—Regeneron” for a description of our license agreement with Regeneron Pharmaceuticals.

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Clinical Product Candidates

UX143 (setrusumab) for the treatment of Osteogenesis Imperfecta, or OI

UX143 (setrusumab) is a fully human monoclonal antibody administered by IV that inhibits sclerostin, a protein that acts on a key bone-signaling pathway by inhibiting the activity of bone-forming cells and promoting bone resorption. Setrusumab is being developed for the treatment of OI, or brittle bone disease, which is caused by variants in the COL1A1 or COL1A2 genes, leading to either reduced or abnormal collagen and changes in bone metabolism. There are an estimated 60,000 patients in the developed world affected by OI. UX143 has received orphan drug designation from the U.S. Food and Drug Administration, or FDA, and European Medicines Agency, or EMA, rare pediatric disease designation from the FDA, and was accepted into the EMA’s Priority Medicines program, or PRIME, program. Setrusumab is subject to our collaboration agreement with Mereo and is the lead clinical asset in our bone endocrinology franchise.

In June 2023, we, along with our collaboration partner, Mereo, announced positive data from the dose-selection Phase 2 portion of the Phase 2/3 Orbit study, which demonstrated that setrusumab rapidly induced bone production in patients aged five to 25 with OI. Across all patients evaluated as of the data cut-off, setrusumab demonstrated statistically significant increases in levels of serum P1NP, a sensitive marker of bone formation, and a substantial and significant improvement in bone mineral density (BMD) by three months.

As of the data cut-off for our June 2023 announcement, serum P1NP levels through at least one month of treatment were available from all 24 patients enrolled in the Phase 2 portion of Orbit and demonstrated that treatment with setrusumab significantly increased serum P1NP in both dosing cohorts, peaking at one to two weeks and again, as expected, after the two-month dosing timepoint. Lumbar spine BMD data were available in 17 of 24 Orbit patients at the 3-month timepoint. Treatment with setrusumab for three months resulted in an increase in lumbar spine BMD from baseline of 9.4% at 20 mg/kg (n=10), which represents a substantial mean change in Z-score of +0.65 from -2.12 (n=11) at baseline.

In October 2023 at the American Society for Bone and Mineral Research 2023 Annual Meeting (ASBMR), we and Mereo announced additional interim data from the Phase 2 portion of the Phase 2/3 Orbit study that demonstrated that treatment with UX143 significantly reduced incidence of fractures in patients with OI with at least six months of follow-up and continued to demonstrate ongoing and meaningful improvements in lumbar spine BMD. As of the data cut-off on August 4, 2023 and following at least six months of treatment with setrusumab, the annualized fracture rate across all 24 patients in the Phase 2 portion of the study was reduced by 67%. The median annualized fracture rate of 0.72 in the two years prior to treatment was reduced to 0.00 (n=24, p=0.042) during the mean treatment duration period of nine months. Such fractures excluded fractures of the fingers, toes, skull and face consistent with the Phase 3 study design. As of the data cut-off for our October 2023 announcement, there were no treatment-related serious adverse events observed in the study.

The Phase 3 portion of the Orbit study is expected to enroll approximately 150 patients and be fully enrolled around the end of the first quarter of 2024. Additional, longer-term Phase 2 data from the Orbit study are expected in 2024. The Phase 3 Cosmic study is an active-controlled study evaluating the effect of setrusumab compared to intravenous bisphosphonate (IV-BP) therapy on annualized total fracture rate in patients aged 2 to <5 years. Cosmic is targeting to enroll approximately 50 patients or more at more than 20 global sites and is expected to complete enrollment in the first half of 2024.

Please see “—License and Collaboration Agreements—Clinical Product Candidates—Mereo” for a description of our license and collaboration agreement with Mereo.

GTX-102 for the treatment of Angelman Syndrome

GTX-102 is an antisense oligonucleotide, or ASO, administered by intrathecal injection (IT) that inhibits expression of the paternal UBE3A antisense. GTX-102 is being developed for the treatment of Angelman syndrome, a debilitating and rare neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene. There are an estimated 60,000 patients in the developed world affected by Angelman syndrome. GTX-102 has received Fast Track Designation, Orphan Drug Designation and Rare Pediatric Disease Designation from the FDA and has been accepted into the EMA’s Priority Medicines program, or PRIME, program.

In May 2023, we announced that the FDA reviewed and agreed to a protocol amendment to the Phase 1/2 study of GTX-102 in pediatric patients with Angelman syndrome that enables us to harmonize dose ranges in the U.S. with those being used in ex-U.S. cohorts of the study. The Phase 1/2, open-label, dose-escalating study is evaluating the safety and tolerability of GTX-102 in pediatric patients with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. The study is looking to verify the GTX-102 dose range and treatment regimen that are expected to be used in the Phase 3 program.

In October 2023, at the Company's Analyst Day, we presented data from the extension cohorts (Cohorts 4-7) in the Phase 1/2 study for GTX-102 that demonstrated clinically meaningful improvements in multiple domains. We presented quantitative data that showed improvements across multiple clinical domains compared to natural history data, where available, and clinical changes were

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associated with quantitative changes in EEG. Long-term data showed patients who stopped and restarted treatment reacquired previously gained developmental skills when they were re-dosed with the current regimen. As of the data cut-off date, October 3, 2023, there had been no additional treatment-related serious adverse events, or SAEs, since November 2022.

In January 2024, we announced that enrollment in the expansion cohorts had been completed with a total of 53 patients enrolled. Across the Phase 1/2, including the dose escalation and expansion cohorts, there are a total of 74 patients enrolled in the Phase 1/2 study. The expansion cohorts will evaluate many of the same safety, pharmacokinetic, and efficacy measures as the previously enrolled dose escalation cohorts plus some new evaluations. The next safety and efficacy data update is expected in the first half of 2024 and is planned to include at least 20 expansion cohort patients with a minimum of Day 170 data.

Please see “—License and Collaboration Agreements—Clinical Product Candidates—GeneTx” for a description of our license agreement with GeneTx.

UX111 for the treatment of Sanfilippo syndrome type A or MPS IIIA

UX111 (formerly ABO-102) is an adeno-associated virus 9, or AAV9, gene therapy product candidate, administered by a one-time IV infusion that provides the cross-correcting enzyme that enables the break down of Heparan sulfate, or HS. UX111 is being developed for the treatment of patients with Sanfilippo syndrome type A, or MPS IIIA, a rare lysosomal storage disease with no approved treatment, which primarily affects the central nervous system. There are an estimated 3,000 to 5,000 patients in the developed world affected by Sanfilippo syndrome type A. The program was acquired through an exclusive license agreement with Abeona Therapeutics, or Abeona, that was announced in May 2022. The UX111 program has received Regenerative Medicine Advanced Therapy, or RMAT, Fast Track, Rare Pediatric Disease, and Orphan Drug Designations in the U.S., and PRIME and Orphan Medicinal Product designations in the EU.

Abeona previously announced the completion of a successful Type B meeting with the FDA regarding the pivotal Transpher A trial to support filing and approval for UX111. Ultragenyx presented new data from the ongoing pivotal Transpher A study evaluating the efficacy and safety of UX111 in children with MPS IIIA at the 20th Annual WORLDSymposiumTM. The presentation showed that the observed reductions of HS exposure in cerebrospinal fluid can predict improved long-term cognitive function in patients with MPS IIIA following treatment with UX111. Discussions with the FDA seeking an accelerated review path are ongoing.

Please see “—License and Collaboration Agreements—Clinical Product Candidates—Abeona” for a description of our license agreement with Abeona.

DTX401 for the treatment of glycogen storage disease type Ia, or GSDIa

DTX401 is an adeno-associated virus 8, or AAV8, gene therapy clinical candidate, administered by a one-time IV infusion that is designed to deliver stable expression and activity of G6Pase-α, an essential enzyme in glycogen and glucose metabolism. DTX401 is being developed for the treatment of patients with glycogen storage disease type Ia, or GSDIa, and is the most common genetically inherited glycogen storage disease, with an estimated 6,000 patients in the developed world. A Pediatric Investigation Plan, or PIP, was accepted by the EMA. The DTX401 program has received RMAT, Fast Track, and Orphan Drug designations in the U.S., and PRIME and Orphan Medicinal Product Designations in the EU. We currently plan to move manufacturing of DTX401 from a third party to our gene therapy manufacturing facility, which could lengthen our timeline to filing a biologics license application, or BLA.

In May 2023, we announced the last patient had been dosed in the Phase 3 study of DTX401. The 48-week study has fully enrolled patients eight years of age and older, randomized 1:1 to DTX401 (1.0 x 10^13 GC/kg dose) or placebo. The primary endpoint is the reduction in oral glucose replacement with cornstarch while maintaining glucose control. We expect to share results from this Phase 3 study in the first half of 2024.

Please see “—License and Collaboration Agreements—Clinical Product Candidates—REGENXBIO Inc.” for a description of our license agreement with REGENXBIO Inc.

DTX301 for the treatment of ornithine transcarbamylase, or OTC, deficiency

DTX301 is an AAV8 gene therapy product candidate, administered by a one-time IV infusion that is designed to deliver stable expression and activity of the ornithine transcarbamylase, or OTC, gene. DTX301 is being developed for the treatment of patients with OTC deficiency, which is the most common urea cycle disorder, and there are approximately 10,000 patients in the developed world with OTC deficiency, of which we estimate approximately 80% are classified as late-onset, our target population. DTX301 has received Orphan Drug Designation in both the U.S. and in the EU and Fast Track Designation in the U.S.

We are currently randomizing and dosing patients in our 64-week Phase 3 study of DTX301. The patients in the study will be randomized 1:1 to DTX301 (1.7 x 10^13 GC/kg dose) or placebo. We plan to enroll approximately 50 patients 12 years of age and older. The co-primary endpoints are the percentage of patients who achieve a response, as measured by discontinuation or

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reduction in baseline disease management, and the 24-hour plasma ammonia levels. We expect to complete enrollment for the Phase 3 study in the first half of 2024.

Please see “—License and Collaboration Agreements—Clinical Product Candidates—REGENXBIO Inc.” for a description of our license agreement with REGENXBIO Inc.

UX701 for the treatment of Wilson Disease

UX701 is an AAV type 9 gene therapy, administered by a one-time IV infusion that is designed to deliver a truncated form of the ATP7B gene. UX701 is being developed for the treatment of patients with Wilson disease, which affects more than 50,000 patients in the developed world. UX701 has received Orphan Drug Designation in the U.S. and in the EU. UX701 has received a Fast Track Designation from the FDA.

In October 2023 at the Company's Analyst Day, we announced that four out of five patients in the first cohort (5.0 x 10^12 GC/kg) had reductions in urinary copper and were tapering off of chelators and/or zinc therapy, including two of three earlier treated patients in the cohort that were then completely off standard of care therapy. As of the data cut-off date, October 8, 2023, UX701 had been generally well tolerated with no treatment-related SAEs.

We have enrolled and dosed patients in the three dose escalating cohorts of the first stage of the pivotal Cyprus2+ study of UX701 for the treatment of Wilson disease. During this stage, the safety and efficacy of UX701 is being evaluated that will enable a dose to be selected for further evaluation in the second, randomized, placebo-controlled stage of this seamless pivotal study. Data from Stage 1 are expected in mid 2024, which will be followed by the initiation and dosing of patients in Stage 2 in the second half of 2024.

Please see “—License and Collaboration Agreements—Clinical Product Candidates— REGENXBIO Inc.” for a description of our license and collaboration agreement with REGENXBIO Inc.

Competition

In the case of indications that we are targeting, it is possible that other companies may produce, develop, and commercialize compounds that might treat these diseases.

With respect to Crysvita, although we are not aware of any other products currently in clinical development for the treatment of XLH and TIO, it is possible that competitors may produce, develop, and commercialize therapeutics, or utilize other approaches such as gene therapy, to treat XLH and TIO. Most pediatric patients with XLH are managed using oral phosphate replacement and/or vitamin D therapy, which is relatively inexpensive and therefore may adversely affect our ability to commercialize Crysvita, if approved, in some countries.

With respect to Mepsevii, we are not aware of any other compounds currently in clinical development for MPS VII, but it is possible that other companies may produce, develop, and commercialize compounds that might treat this disease. Additionally, gene therapy and other therapeutic approaches may emerge for the treatment of lysosomal diseases. Bone marrow or stem cell transplants have also been used in MPS VII and in other lysosomal storage diseases and represent a potential competing therapy. Stem cell transplants have been effective in treating soft tissue storage and in having an impact on brain disease, but have not to date proven effective in treating bone and connective tissue disease. Typically, enzyme replacement therapy has had an impact on bone and connective tissue disease in other disorders when patients were treated early.

With respect to Dojolvi, LC-FAOD is commonly treated with diet therapy and MCT oil. Dojolvi may compete with this approach. Although we believe that Dojolvi should be considered a drug and will be regulated that way, it is possible that other companies or individuals may attempt to produce triheptanoin for use in LC-FAOD. Investigators are testing triheptanoin in clinical studies across multiple indications, including LC-FAOD. It is also possible that other companies may produce, develop, and commercialize other medium odd-chain fatty acids, or completely different compounds, to treat LC-FAOD. Other companies may also utilize other approaches, such as gene therapy, to treat LC-FAOD. In addition, Reneo Pharmaceuticals is developing REN001, a PPAR delta agonist, in Phase 1b for LC-FAOD and other genetic myopathies.

With respect to Evkeeza, the current treatments for patients with HoFH involve various lipid-lowering agents to reduce serum LDL and total cholesterol levels. Drug therapies include statins (e.g., Rosuvastatin, Simvastatin, etc.), fenofibrate, ezetimibe (Ezetrol), evolocumab (Repatha), and lomitapide (Juxtapid/Lojuxta). Other than lomitapide, these agents rely on an LDL-receptor based mechanism to reduce cholesterol, which may be absent in HoFH patients, particularly those with LDLR-null mutations. In addition, Arrowhead Pharmaceuticals is developing ARO-ANG3 and Eli Lilly/Dicerna is developing LY3561774, both RNAi-based inhibitors of ANGPTL3 in Phase 2 studies across various indications including HoFH.

With respect to UX143, there are currently no approved drugs for OI. Most pediatric patients with OI are managed with off-label use of bisphosphonates to increase bone density and reduce frequency of bone fracture. We are aware of another

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anti-sclerostin antibody, romosozumab, that is in Phase 3 clinical testing by Amgen. In addition, two anti-TGFβ antibodies, fresolimumab and SAR439459, are in Phase 1 clinical testing by Sanofi-Genzyme.

With respect to GTX-102, there are currently no approved drugs for Angelman syndrome. Many patients take general treatments to try to manage specific symptoms, such as seizures or sleep disturbances, but there are no treatments available that address the underlying biology of the disease. We are aware of other preclinical and clinical development programs for Angelman syndrome, including Phase 2 programs from Biogen in collaboration with Ionis, ION582 an ASO, and Neuren Pharmaceuticals, NNZ-2591 an IGF-1 analog.

With respect to UX111, there are currently no approved pharmacologic treatments for patients with MPS IIIA. Patients receive supportive or symptomatic treatment, but these approaches generally do not prevent functional decline. We are aware of other gene therapies, including LYS-SAF302, in Phase 2/3 for MPSIIIA by Lysogene, and EGT-101, in Phase 1/2 for MPSIIIA by Esteve. In addition, Orchard Therapeutics is developing OTL-201, an ex-vivo gene therapy in Phase 1/2 for MPSIIIA.

With respect to DTX401, there are currently no pharmacologic treatments for patients with GSDIa. We are aware of an mRNA therapy, mRNA-3745, in Phase 1 for GSDIa by Moderna.

With respect to DTX301, the current treatments for patients with OTC deficiency are nitrogen scavenging drugs and severe limitations in dietary protein. Drug therapy includes sodium phenylbutyrate (Buphenyl) and glycerol phenylbutyrate (Ravicti), both nitrogen scavengers that help eliminate excess nitrogen, in the form of ammonia, by facilitating its excretion. A novel formulation of sodium phenylbutyrate, ACER-001 by Acer Therapeutics, was approved in December 2022. During a metabolic crisis, patients routinely receive carbohydrate and lipid rich nutrition, including overnight feeding through a nasogastric tube, to limit bodily protein breakdown and ammonia production. In acute cases, ammonia must be removed by dialysis or hemofiltration. Liver transplant may also be a solution for OTC deficiency. In addition, Arcturus Therapeutics is developing ARCT-810, a messenger RNA therapy, in Phase 2 for OTC deficiency.

With respect to UX701, there are no currently approved treatments that address the underlying cause of Wilson disease. Many patients are on chelator therapies, but these fail to address the mutated ATP7B copper transporter gene. We are aware of another gene therapy, VTX-801, that is in Phase 1 for Wilson disease by Vivet Therapeutics, in collaboration with Pfizer.

License and Collaboration Agreements

Our products and some of our current product candidates have been either in-licensed from academic institutions or derived from partnerships with other pharmaceutical companies. Following is a description of our significant license and collaboration agreements.

Approved Products

Kyowa Kirin Co., Ltd.

In August 2013, we entered into a collaboration and license agreement with KKC. Under the terms of this collaboration and license agreement, as amended, we and KKC collaborate on the development and commercialization of Crysvita in the field of orphan diseases in the U.S. and Canada, or the Profit-Share Territory, and in the EU, U.K., and Switzerland, or the European Territory, and we have the right to develop and commercialize such products in the field of orphan diseases in Mexico and Central and South America, or Latin America. In the field of orphan diseases, and except for ongoing studies being conducted by KKC, we were the lead party for development activities in the Profit-Share Territory and in the European Territory until the applicable transition date. We shared the costs for development activities in the Profit-Share Territory and the European Territory conducted pursuant to the development plan before the applicable transition date equally with KKC. In April 2023, which was the transition date for the Profit-Share Territory, KKC became the lead party and became responsible for the costs of the development activities. However, we will continue to share the costs of the studies commenced prior to the applicable transition date equally with KKC. Crysvita was approved in the EU and U.K. in February 2018 and was approved by the FDA in April 2018. As described below, we and KKC shared commercial responsibilities and profits in the Profit-Share Territory until April 2023, KKC has the commercial responsibility in the European Territory, and we are responsible for commercializing Crysvita in Latin America.

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In the Profit-Share Territory, KKC booked sales of products and we had the sole right to promote the products, with KKC having the right to increasingly participate in the promotion of the products until the transition date of April 2023, which was five years from commercial launch. In 2022, we entered into an amendment to the collaboration agreement which granted us the right to continue to support KKC in commercial field activities in the U.S. through April 2024, subject to the limitations and conditions set forth in the amendment. The parties subsequently mutually agreed to extend our right to continue to support KKC in commercial field activities in the U.S. through December 31, 2024, and as a result, we will continue to support commercial field efforts in the U.S. through a cost share arrangement through December 2024. After December 31, 2024, our rights to promote Crysvita in the U.S. will be limited to medical geneticists and we will solely bear our expenses for the promotion of Crysvita in the Profit-Share Territory. See “Item I.A. Risk Factors” for additional information on the risks related to the expiration of our exclusive right to promote Crysvita in the Profit-Share Territory. In the European Territory, KKC books sales of products and has the sole right to promote and sell the products, with the exception of Turkey. In Turkey, we have rights to commercialize Crysvita and KKC has the option to assume responsibility for such commercialization efforts, after a certain minimum period. In Latin America, we book sales of products and have the sole right to promote and sell the products.

Under the collaboration agreement, KKC manufactures and supplies Crysvita for sales in Latin American territories and we pay KKC a transfer price of 30% of net sales. Prior to December 31, 2022, the transfer price on net sales was 35%. We also pay KKC a low single-digit royalty on net sales in Latin America. The remaining profit or loss from commercializing products in the Profit-Share Territory was shared between us and KKC on a 50/50 basis until April 2023. In April 2023, commercialization responsibilities for Crysvita in the Profit-Share Territory transitioned to KKC and KKC assumed responsibility for the commercialization of Crysvita in the Profit-Share Territory at and after April 2023. Thereafter, we are entitled to receive a tiered double-digit revenue share from the mid-20% range up to a maximum rate of 30%, intended to approximate the profit-share. Our and KKC’s obligations to pay royalties will continue on a country-by-country basis for so long as we or KKC, as applicable, are selling products in such country.

In July 2022, we sold to OCM LS23 Holdings LP, an investment vehicle for the Ontario Municipal Employees Retirement System, or OMERS, our right to receive 30% of the future royalty payments due to us based on net sales of Crysvita in the U.S. and Canada, subject to a cap, beginning in April 2023. KKC pays us a royalty of up to 10% based on net sales in the European Territory. We sold our interest in the European Territory royalty to RPI Finance Trust, an affiliate of Royalty Pharma, in December 2019.

The collaboration and license agreement will continue for as long as products in the field of orphan diseases are sold in the Profit-Share Territory, European Territory, Turkey, or Latin America, unless the agreement is terminated in accordance with its terms.

KKC may terminate the agreement in certain countries or territories based upon our failure to meet certain milestones. Furthermore, either party may terminate the agreement for the material breach or bankruptcy of the other party. In any event of termination by KKC, unless such termination is the result of KKC’s termination for certain types of breach of the agreement by us, we may receive low single-digit to low double-digit royalties on net post-termination sales by KKC in one or more countries or territories, the amount of which varies depending on the timing of, and reason for, such termination. In any event of termination, our rights to Crysvita under the agreement and our obligations to share development costs will cease, and the program will revert to KKC, worldwide if the agreement is terminated as a whole or solely in the terminated countries if the agreement is terminated solely with respect to certain countries.

Saint Louis University

In November 2010, we entered into a license agreement with Saint Louis University, or SLU, wherein SLU granted us certain exclusive rights to intellectual property related to Mepsevii. Under the terms of the license agreement, SLU granted us an exclusive worldwide license to make, have made, use, import, offer for sale, and sell therapeutics related to SLU’s beta-glucuronidase product for use in the treatment of human diseases.

Under the license agreement, we are obligated to pay to SLU a low single-digit royalty on net sales of the licensed products in the U.S., Europe, or Japan, subject to certain potential deductions. Our obligation to pay royalties to SLU in these territories continues until the expiration of any orphan drug exclusivity.

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Baylor Research Institute

In September 2012, we entered into a license agreement, which was subsequently amended, with Baylor Research Institute, or BRI, under which we exclusively licensed certain intellectual property related to Dojolvi. The license includes patents, patent applications, know-how, and intellectual property related to the composition and formulation of Dojolvi as well as its use in treating a number of orphan diseases, including LC-FAOD. The license grant includes the sole right to develop, manufacture, and commercialize licensed products for all human and animal uses. Under the license agreement, we are obligated to use commercially reasonable efforts to develop and commercialize licensed products in select orphan indications. If we fail to meet our diligence obligations with respect to a specified orphan indication or set of orphan indications, BRI may convert our license to a non-exclusive license with respect to such orphan indication or set of orphan indications until we receive regulatory approval for licensed products in the applicable orphan indication or set of orphan indications.

We are also obligated to pay a mid- single-digit royalty on net sales to BRI, subject to certain reductions and offsets. Our obligation to pay royalties to BRI continues on a licensed product-by-licensed product and country-by-country basis until the later of the expiration of the first regulatory exclusivity granted with respect to such product in such country or the expiration of the last-to-expire licensed patent claiming such product in such country, in each case in connection with approval in such country for LC-FAOD or an orphan disease covered by our license from BRI. During the year ended December 31, 2022, the sales milestone triggering a $2.5 million payment was achieved. Going forward, we may make future payments of up to $2.5 million contingent upon attainment of certain development milestones and $5.0 million if certain sales milestones are achieved.

Regeneron

In January 2022, we announced a collaboration with Regeneron to commercialize Evkeeza for HoFH outside of the U.S. Evkeeza is approved in the U.S., where it is marketed by Regeneron, and in the EU and U.K. as a first-in-class therapy for use together with diet and other low-density lipoprotein-cholesterol-lowering therapies to treat adults and adolescents aged 12 years and older with HoFH. Pursuant to the terms of the agreement, we received the rights to develop, commercialize and distribute the product for HoFH in countries outside of the U.S. Upon closing of the transaction in January 2022, we paid Regeneron a $30.0 million upfront payment. During the year ended December 31, 2023, a $10.0 million regulatory milestone was achieved. Going forward, we are obligated to pay Regeneron up to $53.0 million in future milestone payments, contingent upon the achievement of certain regulatory and sales milestones. We may share in certain costs for global trials led by Regeneron and also received the right to opt into other potential indications.

Under the collaboration agreement, Regeneron supplies the product and charges us a transfer price from the low 20% range up to 40% of net sales.

Clinical Product Candidates

REGENXBIO Inc.

In October 2013, we entered into an exclusive license agreement with REGENXBIO Inc., or REGENX, under which we were granted an option to develop products to treat hemophilia A, OTC deficiency and GSDIa. Under the 2013 license agreement, REGENX granted us an exclusive worldwide license to make, have made, use, import, sell, and offer for sale licensed products with respect to such disease indications, subject to certain exclusions. We do not have the right to control prosecution of the in-licensed patent applications, and our rights to enforce the in-licensed patents are subject to certain limitations. Under the 2013 license agreement, we pay or will pay REGENX an annual maintenance fee and certain milestone fees per disease indication, low to mid- single-digit royalty percentages on net sales of licensed products, and milestone and sublicense fees, if any, owed by REGENX to its licensors as a result of our activities under the 2013 license agreement. We are required to develop licensed products in accordance with certain milestones. In the event that we fail to meet a particular milestone within established deadlines, we can extend the relevant deadline by providing a separate payment to REGENX.

In March 2015, we entered into an option and license agreement with REGENX, which was subsequently amended, pursuant to which we have an exclusive worldwide license to make, have made, use, import, sell, and offer for sale licensed products to treat Wilson disease and CDKL5 deficiency. We do not have the right to control prosecution of the in-licensed patent applications, and our rights to enforce the in-licensed patents are subject to certain limitations. Under the 2015 option and license agreement, as amended, we pay or will pay REGENX an annual maintenance fee and certain milestone fees per disease indication, mid- to high single-digit royalty percentages on net sales of licensed products, and mid- single to low double-digit percentages of any sublicense fees we receive from sublicenses for the licensed intellectual property rights. We are required to develop licensed products in accordance with certain milestones. In the event that we fail to meet a particular milestone within established deadlines, we can extend the relevant deadline by providing a separate payment to REGENX.

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In March 2020, we entered into a license agreement with REGENX, for an exclusive, sublicensable, worldwide license to REGENX’s NAV AAV8 and AAV9 vectors for the development and commercialization of gene therapy treatments for a rare metabolic disorder. In return for these rights, we made an upfront payment and pay or will pay certain annual fees, milestone payments and royalties on any net sales of products incorporating the licensed intellectual property that range from a high single-digit to low double-digit.

University of Pennsylvania

In May 2016, we entered into a research, collaboration and license agreement with the University of Pennsylvania under which we are collaborating on the pre-clinical development of gene therapy products for the treatment of phenylketonuria and Wilson disease, each, a Subfield. Under the agreement, we were granted an exclusive, worldwide, royalty-bearing right and license to certain patent rights arising out of the research program, and a non-exclusive, worldwide, royalty-bearing right and license to certain University of Pennsylvania intellectual property, in each case to research, develop, make, have made, use, sell, offer for sale, commercialize and import licensed products in each Subfield for the term of the agreement. We will fund the cost of the research program and will be responsible for clinical development, manufacturing and commercialization of each Subfield. In addition, we are required to make milestone payments (up to a maximum of $5.0 million per Subfield) if certain development milestones are achieved over time. We will also make milestone payments of up to $25.0 million per approved product, if certain commercial milestones are achieved, and will pay low to mid- single-digit royalties on net sales of each Subfield’s licensed products.

GeneTx

In August 2019, we entered into a Program Agreement and a Unitholder Option Agreement with GeneTx Biotherapeutics LLC, or GeneTx, to collaborate on the development of GeneTx’s GTX-102, an ASO for the treatment of Angelman syndrome. In July 2022, pursuant to the terms of the Unitholder Option Agreement, as amended, we exercised the Option to acquire GeneTx and entered into a Unit Purchase Agreement, or the Purchase Agreement, pursuant to which we purchased all the outstanding units of GeneTx. In accordance with the terms of the Purchase Agreement, we paid the option exercise price of $75.0 million, an additional $15.6 million to acquire the outstanding cash of GeneTx, and adjustments for working capital and transaction expenses of $0.6 million, for a total purchase consideration of $91.2 million. We may be required to make payments of up to $190.0 million upon the achievement of certain milestones, including up to $30.0 million in milestone payments upon achievement of the earlier of initiation of a Phase 3 clinical study or product approvals in Canada and the U.K., up to $85.0 million in additional regulatory approval milestones for the achievement of U.S. and EU product approvals, and up to $75.0 million in commercial milestone payments based on annual worldwide net product sales. We will also pay tiered mid- to high single-digit percentage royalties based on licensed product annual net sales. If we receive and resell an FDA priority review voucher, or PRV, in connection with a new drug application approval, GeneTx is entitled to receive a portion of proceeds from the sale of the PRV or a cash payment from us, if we choose to retain the PRV. As part of our acquisition of GeneTx, we assumed a License Agreement with Texas A&M University, or TAMU. Under this agreement, TAMU is eligible to receive from us up to $23.5 million upon the achievement of various future milestones, a nominal annual license fee that may increase up to a maximum of $2.0 million, as well as royalties in the mid-single-digits of net sales.

Mereo

In December 2020, we entered into a License and Collaboration Agreement with Mereo to collaborate on the development of setrusumab. Under the terms of the agreement, we will lead future global development of setrusumab in both pediatric and adult patients with OI and were granted an exclusive license to develop and commercialize setrusumab in the U.S., Turkey, and the rest of the world, excluding the European Economic Area, United Kingdom, and Switzerland, or the Mereo Territory, where Mereo retains commercial rights. Each party will be responsible for post-marketing commitments and commercial supply in their respective territories.

Upon the closing of the transactions under the License and Collaboration Agreement with Mereo in January 2021, we made a payment of $50.0 million to Mereo. During the year ended December 31, 2023, we made a $9.0 million payment to Mereo upon the achievement of a clinical milestone. Going forward, we may be required to make payments of up to $245.0 million upon the achievement of certain clinical, regulatory, and commercial milestones. We will pay for all global development costs as well as tiered double-digit percentage royalties to Mereo on net sales in the U.S., Turkey, and the rest of the world, and Mereo will pay us a fixed double-digit percentage royalty on net sales in the Mereo Territory.

Abeona

In May 2022, we announced an exclusive License Agreement with Abeona for an AAV gene therapy for the treatment of MPS IIIA, or UX111. Under the terms of the agreement, we assumed responsibility for the UX111 program and in return, we are obligated

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to pay Abeona certain UX111-related prior development costs and other transition costs. Abeona is eligible to receive tiered royalties of up to 10% on net sales and commercial milestone payments of up to $30.0 million following regulatory approval of the product. Additionally, we entered into an Assignment and Assumption Agreement with Abeona to transfer and assign to us the exclusive license agreement between Nationwide Children’s Hospital, or NCH, and Abeona for certain rights related to UX111. Under this agreement, NCH is eligible to receive from us up to $1.0 million in development and regulatory milestones as well as royalties in the low single-digits of net sales.

Preclinical Pipeline

Solid Biosciences Inc.

In October 2020, we entered into a strategic Collaboration and License Agreement with Solid Biosciences Inc., or Solid, and received an exclusive license for any pharmaceutical product that expresses Solid’s proprietary microdystrophin construct from AAV8 and variants thereof in clade E for use in the treatment of Duchenne muscular dystrophy and other diseases resulting from lack of functional dystrophin, including Becker muscular dystrophy. We are collaborating to develop products that combine Solid’s differentiated microdystrophin construct, our Pinnacle PCLTM producer cell line platform, or Pinnacle PCL Platform, manufacturing platform, and our AAV8 variants. Solid may provide some development support and was granted an exclusive option to co-invest in products we develop for profit-share participation in certain territories. We also entered into a Stock Purchase Agreement with Solid in October 2020 pursuant to which we purchased 521,719 shares (as adjusted for the October 2022 reverse stock split) of Solid’s common stock for an aggregate price of $40.0 million.

Patents and Proprietary Rights

The proprietary nature of, and protection for, our products, product candidates, processes, and know-how are important to our business. Our success depends in part on our ability to protect our products, product candidates, processes, and know-how, to operate without infringing on the proprietary rights of others, and to prevent others from infringing our proprietary rights. We seek patent protection in the U.S. and internationally for our products, product candidates, and processes. Our policy is to patent or in-license the technologies, inventions, and improvements that we consider important to the development of our business. In addition to patent protection, we rely on trade secrets, know-how, and continuing innovation to develop and maintain our competitive position.

We also use other means to protect our products and product candidates, including the pursuit of marketing or data exclusivity periods, orphan drug status, and similar rights that are available under regulatory provisions in certain countries, including the U.S., Europe, Japan, and China. See “Government Regulation—U.S. Government Regulation — Orphan Designation and Exclusivity,” “Government Regulation—U.S. Government Regulation — Pediatric Studies and Exclusivity,” “Government Regulation—U.S. Government Regulation — Biosimilars and Exclusivity,” “Government Regulation—U.S. Government Regulation — Abbreviated New Drug Applications for Generic Drugs and New Chemical Entity Exclusivity,” “Government Regulation—U.S. Government Regulation — Patent Term Restoration,” “Government Regulation—EU Regulation — Orphan Designation and Exclusivity,” and “Government Regulation—EU Regulation — New Chemical Entity Exclusivity” below for additional information.

We seek regulatory approval for our products and product candidates in disease areas with high unmet medical need, significant market potential, and where we expect to have a proprietary position through patents covering various aspects of our product candidates, such as composition, dosage, formulation, use, and manufacturing process, among others. Our success depends in part on an intellectual property portfolio that supports our future revenue streams and erects barriers to our competitors. We are maintaining and building our patent portfolio by filing new patent applications, prosecuting existing applications, and licensing and acquiring new patents and patent applications.

Despite these measures, any of our intellectual property and proprietary rights could be challenged, invalidated, circumvented, infringed, or misappropriated, or such intellectual property and proprietary rights may not be sufficient to achieve or maintain market exclusivity or otherwise to provide competitive advantages. We also cannot be certain that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future, nor can we be sure that any of our existing patents or any patents granted to us in the future will be commercially useful in protecting our products, product candidates, or processes. For more information, please see “Item I.A. Risk Factors Risks Related to Our Intellectual Property.”

As of December 31, 2023, we own, jointly own, or have exclusive rights to more than 250 issued and in-force patents (not including individually validated national patents in European Patent Convention member countries) that cover one or more of our products or product candidates, methods of their use, or methods of their manufacture, including more than 50 in-force patents issued by the U.S. Patent and Trademark Office, or the USPTO. Furthermore, as of December 31, 2023, we own, jointly own, or have exclusive rights to more than 350 pending patent applications, including more than 50 pending U.S. applications.

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With respect to our owned or in-licensed issued patents in the U.S. and Europe, we may be entitled to obtain an extension of patent term to extend the patent expiration date. For example, in the U.S., this extended coverage period is known as patent term extension, or PTE, and can only be obtained provided we apply for and receive a marketing authorization for a product. The period of extension may be up to five years beyond the expiration of the patent, but cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval. Only one patent among those eligible for an extension may be extended. In Europe, a Supplementary Protection Certificate, or SPC, may be available to extend the term of certain European patents covering our products; this requires application for an SPC in individual European Patent Convention, or EPC, member countries following product approval. However, there is no guarantee that the applicable authorities, including the FDA, will agree with our assessment of whether such extensions should be granted, and even if granted, the length of such extensions. In the U.S., the exact duration of the extension depends on the time we spend in clinical studies as well as getting marketing approval from the FDA.

The exclusivity positions for our commercial products and our clinical-stage product candidates as of December 31, 2023, are summarized below.

Crysvita (Burosumab) Exclusivity

We have in-licensed rights from KKC to patents and patent applications relating to Crysvita and its use for the treatment of XLH, TIO, and various other hypophosphatemic conditions. Pursuant to this license, we have rights to six issued U.S. patents, as well as issued patents and patent applications in other jurisdictions. The U.S. patents expire between 2028 and 2035. In addition to the foregoing patent protections, Crysvita is protected in the U.S. by regulatory exclusivity until 2030 and by orphan drug exclusivity for treating XLH and TIO until 2025 and 2027, respectively.

Mepsevii (Vestronidase Alfa) Exclusivity

We own four issued U.S. patents and corresponding issued foreign patents covering Mepsevii and its use in the treatment of lysosomal storage disorders such as MPS VII. These patents expire in 2035. Mepsevii is also protected in the U.S. by regulatory exclusivity until 2029 and by orphan drug exclusivity for treating MPS VII until November 2024.

Dojolvi (Triheptanoin) Exclusivity

We have an exclusive license from BRI to patents and patent applications relating to Dojolvi and its use for the treatment of FAOD. Pursuant to this license, we have rights to two issued U.S. patents covering Dojolvi which expire in 2025 and 2029. Beyond the patent portfolio in-licensed from BRI, we own a pending U.S. patent application, corresponding foreign patent applications, and issued patents in Australia, Brazil, Canada, Israel, Korea, Malaysia, and Taiwan relating to our pharmaceutical-grade Dojolvi composition; these owned patents and any additional patents issuing from these owned applications are expected to expire in 2034. Dojolvi is also protected in the U.S. by regulatory exclusivity until 2025 and orphan drug exclusivity for treating FAOD until 2027.

Evkeeza (Evinacumab) Exclusivity

We have an exclusive license from Regeneron to certain Regeneron patents for the development and commercialization of Evkeeza outside of the U.S. for the treatment of HoFH and other hyperlipidemia/hypercholesterolemia indications. The in-licensed Regeneron patent portfolio includes a patent family containing several issued foreign patents that expire in 2032 and cover the Evkeeza antibody; Regeneron has filed supplementary protection certificates to extend the rights associated with the European patent within this family until 2036 in certain countries. The in-licensed Regeneron patent portfolio contains five other patent families, one of which includes several pending patent applications directed to a stabilized pharmaceutical formulation comprising Evkeeza; we expect any patents emanating from this patent family to expire in 2040. In addition to the foregoing patent protections, Evkeeza is protected in Europe by data exclusivity until 2029 and marketing exclusivity until 2031.

DTX401 (Pariglasgene Brecaparvovec) Exclusivity

We have two in-licenses to patents and patent applications covering elements of our DTX401 product candidate. First, we have in-licensed an issued U.S. patent owned by the University of Pennsylvania, or UPENN, and sublicensed to us by REGENX relating to the AAV8 capsid used in DTX401 that expired in January 2024. Second, we have a non-exclusive license from the National Institutes of Health, or NIH, to an issued U.S. patent expiring in 2034 (not accounting for any available PTE) and corresponding foreign patents covering a recombinant nucleic acid construct used in DTX401 that includes a codon-optimized version of the G6Pase gene.

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DTX301 (Avalotcagene Ontaparvovec) Exclusivity

We have a license to two patent families covering elements of our DTX301 product candidate. These patent families are owned by UPENN and sublicensed to us by REGENX. The in-licensed UPENN patent portfolio includes an issued U.S. patent relating to the AAV8 capsid used in DTX301 that expired in January 2024, as well as three issued U.S. patents expiring in 2035 (not accounting for any available PTE) and corresponding foreign patents and patent applications covering the codon-optimized version of the OTC gene used in DTX301.

UX143 (Setrusumab) Exclusivity

We have in-licensed rights from Mereo to patents and patent applications relating to setrusumab and its use for the treatment of OI. Pursuant to our license from Mereo, we have exclusive rights outside of Europe to a Mereo patent family that includes three issued U.S. patents and corresponding issued foreign patents that relate to the setrusumab antibody, nucleic acids encoding setrusumab, processes for producing setrusumab, and setrusumab’s use as a medicament. Patents emanating from this patent family expire in 2028 (not accounting for any available PTE). We also have exclusive rights outside of Europe to two additional Mereo patent families, including an issued U.S. patent expiring in 2037 (not accounting for any available PTE), relating to methods of using anti-sclerostin antibodies including setrusumab for the treatment of OI. Beyond these Mereo patents and patent applications, we jointly own with Mereo a patent family relating to dosing regimens for the use of anti-sclerostin antibodies including setrusumab in the treatment of OI; we expect any patents emanating from this patent family to expire in 2042 (not accounting for any available PTE).

UX111 Exclusivity

We have an exclusive license from Nationwide Children’s Hospital, or NCH, to a pending U.S. patent application covering a method of treating MPS IIIA by intravenously administering a recombinant AAV9 vector comprising a U1a promoter and a polynucleotide sequence encoding N-sulfoglucosamine sulfohydrolase, or SGSH; we expect any patent emanating from this application to expire in 2032 (not accounting for any available PTE).

GTX-102 Exclusivity

We have an exclusive license from TAMU to a patent family filed in the U.S. and several foreign jurisdictions relating to UBE3A antisense oligonucleotides including GTX-102 and their use for the treatment of Angelman syndrome. The in-licensed TAMU patent family includes three issued U.S. patents expiring in 2038 (not accounting for any available PTE).

UX701 Exclusivity

We have two licenses to patents and patent applications covering elements of our UX701 product candidate. First, we have in-licensed patents owned by UPENN and sublicensed to us by REGENX relating to the AAV9 capsid used in UX701 that expire between September 2024 and 2026 in the U.S., and in September 2024 in foreign countries. Second, we have an exclusive license from UPENN to a patent family filed in the U.S. and several foreign jurisdictions relating to AAV vectors containing certain regulatory and coding sequences packaged in UX701; this patent family includes an issued U.S. patent expiring in 2039 (not accounting for any available PTE). Beyond these in-licenses, we own a patent family covering AAV vectors expressing a novel truncated version of the ATP7B protein produced by UX701; we expect any patents emanating from this patent family to expire in 2040 (not accounting for any available PTE).

Trademarks

We own registered trademarks covering the Ultragenyx word mark in the U.S. and multiple other jurisdictions. In addition, we have a pending trademark application in the U.S. covering a stylized design of our Ultragenyx logo. We also own registered trademarks in the U.S. and other territories relating to our Mepsevii and Dojolvi brand names for vestronidase alfa and triheptanoin, respectively. We additionally have licenses from KKC and Regeneron to registered trademarks covering the Crysvita and Evkeeza brand names, respectively, in territories where we have rights to commercialize these products.

Other

We rely upon unpatented trade secrets, know-how, and continuing technological innovation to develop and maintain our competitive position. We seek to protect our ownership of know-how and trade secrets through an active program of legal mechanisms including assignments, confidentiality agreements, material transfer agreements, research collaborations, and licenses.

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Manufacturing

While we currently contract with third parties for the manufacturing and testing of most of our products and product candidates for use in preclinical, clinical, and commercial applications, we opened our first GMP manufacturing facility based in Bedford, Massachusetts in June 2023. This facility is focused on drug substance and drug product manufacturing of AAV gene therapy products and will support our clinical and commercial pipeline. This new capability will combine with our existing gene therapy process and analytical development and QC lab capabilities in nearby Woburn, Massachusetts to form a fully integrated gene therapy development, manufacturing, and testing unit.

The use of contracted manufacturing and reliance on collaboration partners has historically minimized our direct investment in manufacturing facilities and additional staff early in development. Although we rely on contract manufacturers, we have personnel with extensive manufacturing experience to oversee our contract manufacturers. All of our third-party manufacturers are subject to periodic audits to confirm compliance with applicable regulations and must pass inspection before we can manufacture our drugs for commercial sales.

For the other non-gene therapy modalities, we primarily use third-party manufacturers to meet our projected needs for commercial manufacturing. Third parties with whom we currently work might need to increase their scale of production, or we will need to secure alternate suppliers. We believe that there are alternate sources of supply that can satisfy our clinical and commercial requirements, although we cannot be certain that identifying and establishing relationships with such sources, if necessary, would not result in significant delay or material additional costs.

Products

Mepsevii

The Mepsevii drug substance is manufactured by Rentschler Biopharma SE, or Rentschler, under non-exclusive commercial supply and services agreements effective December 2017 and January 2018, respectively. The drug substance agreement had an initial term of five years, which was automatically extended for another five years following the initial term and will continue in full force and effect for its term unless earlier terminated. Following the initial term, we and Rentschler can withdraw from the agreement without cause upon prior notice for specified periods. In addition, either party may terminate the agreement if the other party breaches a material provision and such breach remains uncured for a specified period following receipt by the breaching party of written notice of such breach. We can also terminate the agreement if Rentschler loses the right to operate under the agreement. Either party can also terminate the agreements if Rentschler is unable to deliver its agreed upon services for a certain period in the case of a force majeure event. The cell line to produce Mepsevii is specific for this product and is in our control and stored in multiple secure locations. All other raw materials are commercially available. We transferred the fill and finish activities for the manufacture of Mepsevii drug product to a new site, BSP Pharmaceuticals S.p.A., or BSP, located in Latina, Italy as the Rentschler manufacturing site in Laupheim, Germany was discontinued. The site change was approved by relevant global authorities, including the FDA, on May 5, 2022. Sufficient inventory levels were maintained during the transfer of the fill and finish activities for Mepsevii to BSP.

Crysvita

The drug substance and drug product for burosumab are made by KKC in Japan under the collaboration and license agreement with KKC. The cell line to produce burosumab is specific for this product and is in KKC’s control. All other raw materials are commercially available.

Dojolvi

The pharmaceutical-grade drug substance for Dojolvi is manufactured by IOI Oleo GmbH, or IOI Oleo, in Germany under an exclusive worldwide supply agreement, subject to certain limitations, executed in 2012 and subsequently amended and restated in 2023. The agreement has an indefinite term but can be terminated by either party with 36 months prior notice. Additionally, if a party materially breaches an obligation under the agreement and does not cure such breach within 60 days of receiving notice of the breach from the non-breaching party, the non-breaching party may terminate the agreement immediately upon written notice to the breaching party.

In March 2023, the Dojolvi drug product, or DP, manufacturer Aenova Haupt Pharma Wolfratshausen GmbH, or Haupt Pharma notified us of their intent to close the facility by the end of 2023. In response to this information, we produced additional DP batches prior to the facility closure at the end of 2023 and have identified a new DP manufacturer. We are currently in the process of qualifying the new DP manufacturer and conducting transfer activities and expect to complete these activities before the end of 2024. Our current DP inventories are expected to support demand through at least the end of 2025.

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Evkeeza

On January 7, 2022, we announced a license and collaboration agreement with Regeneron for us to clinically develop, commercialize and distribute Evkeeza in countries outside of the U.S. Evkeeza is a fully human monoclonal antibody that binds to and blocks the function of angiopoietin-like 3, or ANGPTL3, a protein that plays a key role in lipid metabolism.

The Evkeeza drug substance is manufactured by Regeneron at their manufacturing facility in Rensselaer, New York and the drug product is manufactured by Baxter Pharmaceutical Solutions, LLC. at their manufacturing facility in Bloomington, Indiana. Release testing of the drug product is performed by Regeneron and third-party suppliers.

We utilize third-party suppliers to perform packaging, labelling, distribution, and testing as needed for Evkeeza.

Product Candidates

The drug substances and drug products for our product candidates are manufactured using our network of GMP contract manufacturing organizations, or CMOs, which are carefully selected and actively managed for high quality, reliable clinical supply. The CMOs are located in Western Europe or North America.

Commercialization and Product Support

We have built our own commercial organizations in North America, Europe, Latin America and Japan to effectively support the commercialization of our products and product candidates, if approved. Our intention is to expand our product portfolio and its geographic accessibility through the continued development of our proprietary pipeline or through strategic partnerships. We may elect to utilize strategic partners, distributors, or contract management organizations to assist in the commercialization of our products in certain geographies. The commercial infrastructure for rare disease products typically consists of a targeted, specialty field organization that educates a limited and focused group of physicians supported by field management and internal support teams, which includes marketing, patient support services, distribution, and market access. One challenge, unique to commercializing therapies for rare diseases, is the difficulty in identifying eligible patients due to the very small and sometimes heterogeneous patient populations along with often undefined clinical or genetic tests to confirm diagnosis. Our commercial and medical affairs teams focus on maximizing patient identification for both clinical development and commercialization purposes in rare diseases.

Additional capabilities important to the rare disease marketplace in the U.S. include the management of key stakeholders such as managed care organizations, specialty pharmacies, specialty distributors, and government payers. In many countries outside the U.S. single national payers are critical to providing reimbursement access. To develop the appropriate commercial infrastructure, we will have to invest a significant amount of financial and management resources, some of which will be committed prior to regulatory approval of the products that they are intended to support.

We continue to support commercial and medical affairs organizations as well as other capabilities across North America, Europe, Latin America, and Japan to meet the educational needs of the healthcare providers and patients in the rare disease community, focusing on providing accurate disease state information and balanced product information across our portfolio for appropriate management of patients with rare disorders.

Medical affairs is comprised of the following capabilities in support of our mission: medical information, patient advocacy, patient diagnosis liaisons, medical science liaisons, research and educational grants. Medical affairs will engage as early as Phase 1 and will continue work throughout the lifecycle of each product and product candidate as dictated by the specific scientific needs in each therapeutic area.

Government Regulation

Government authorities in the U.S. (including federal, state, and local authorities) and in other countries, extensively regulate, among other things, the manufacturing, research and clinical development, marketing, labeling and packaging, storage, distribution, post-approval monitoring and reporting, advertising and promotion, pricing, and export and import of pharmaceutical products, such as those we are developing. We must obtain the requisite approvals from regulatory authorities in the U.S. and foreign countries prior to the commencement of clinical studies or marketing of the product in those countries. Accordingly, our operations are and will be subject to a variety of regulations and other requirements, which vary from country to country. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local, and foreign statutes and regulations require the expenditure of substantial time and financial resources that has a significant impact on our capital expenditures and results of operations.

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Global Regulation of Clinical Studies

Clinical studies involve the administration of an investigational medicinal product to human subjects under the supervision of qualified investigators in accordance with protocols, Good Clinical Practices, or GCP, the ethical principles that have their origin in the Declaration of Helsinki and applicable regulatory requirements. A protocol for each clinical study and any subsequent protocol amendments are typically submitted to the FDA or other applicable regulatory authorities as part of an investigational new drug application, or IND, or clinical trial application, or CTA. Additionally, approval must also be obtained from each clinical study site’s institutional review board, or IRB, or Ethics Committee, or EC, before the studies may be initiated, and the IRB or EC must monitor the study until completed. There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries.

The clinical investigation of a drug is generally divided into three or four phases. Although the phases are usually conducted sequentially, they may overlap or be combined.

•Phase 1. The drug is initially introduced into healthy human subjects or patients with the target disease or condition. These studies are designed to evaluate the safety, dosage tolerance, pharmacokinetics, and pharmacologic actions of the investigational new drug in humans, and if possible, to gain early evidence on effectiveness.

•Phase 2. The drug is administered to a limited patient population to evaluate dosage tolerance and optimal dosage, identify possible adverse side effects and safety risks, and preliminarily evaluate efficacy.

•Phase 3. The drug is administered to an expanded patient population, generally at geographically dispersed clinical study sites to generate enough data to statistically evaluate dosage, clinical effectiveness, and safety, to establish the overall benefit-risk relationship of the investigational new drug product, and to provide an adequate basis for product approval.

•Phase 4. In some cases, additional studies and patient follow-up are conducted to gain experience from the treatment of patients in the intended therapeutic indication. Regulatory authorities may condition approval of a marketing application for a product candidate on the sponsor’s agreement to conduct additional clinical studies after approval. In other cases, a sponsor may voluntarily conduct additional clinical studies after approval to gain more information about the drug. Such post-approval studies are typically referred to as Phase 4 clinical studies.

A pivotal study is a clinical study that adequately meets regulatory authority requirements for the evaluation of a drug candidate’s efficacy and safety such that it can be used to justify the approval of the product. Generally, pivotal studies are Phase 3 studies, but regulatory authorities may accept results from Phase 2 studies if the study design provides a well-controlled and reliable assessment of clinical benefit, particularly in situations where there is an unmet medical need and the results are sufficiently robust.

U.S. Government Regulation

In the U.S., the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, or FDCA, and its implementing regulations, and biologics under the FDCA and the Public Health Service Act, or PHSA, and its implementing regulations. FDA approval is required before any new drug or dosage form, including a new use of a previously approved drug, can be marketed in the U.S. Drugs and biologics are also subject to other federal, state, and local statutes and regulations.

The process required by the FDA before product candidates may be marketed or sold in the U.S. generally involves the following:

•completion of extensive preclinical laboratory tests and preclinical animal studies performed in accordance with the Good Laboratory Practices, or GLP, regulations and the U.S. Department of Agriculture’s Animal Welfare Act;

•submission to the FDA of an IND, which must become effective before human clinical studies may begin and must be updated annually;

•conducting adequate and well-controlled human clinical studies that generally follow the three- to four-phase design described above to establish the safety and efficacy, or for BLA products, the safety, purity, and potency, of the product candidate for each proposed indication under an active IND and approved by an independent IRB representing each clinical site;

•preparation of and submission to the FDA of a new drug application, or NDA, or biologics license application, or BLA, after completion of all pivotal clinical studies;

•potential review of the product application by an FDA advisory committee, where appropriate and if applicable;

•satisfactory completion of an FDA pre-approval inspection of the manufacturing facilities where the proposed drug substance and drug product are produced to assess compliance with Good Manufacturing Practices, or GMP;

•FDA inspection of one or more clinical sites to assure compliance with GCP; and

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•FDA review and approval of an NDA or BLA.

Submission of an NDA or BLA to the FDA

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, detailed investigational new drug product information is submitted to the FDA in the form of an NDA or BLA requesting approval to market the product for one or more indications. Under federal law, the submission of most NDAs and BLAs is subject to a significant application user fee, unless waived.

Pursuant to Title 21 of the Code of Federal Regulations, the FDA conducts a preliminary review of an NDA within 60 days of receipt. FDA procedures provide that the FDA will inform the sponsor by the 74th day after the FDA’s receipt of submission to determine whether the application is sufficiently complete to permit substantive review. The FDA may request additional information rather than accept an NDA for filing, in which case the application must be resubmitted with the requested additional information. The resubmitted application is also subject to review before it is accepted for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review.

Once an NDA or BLA has been accepted, the FDA’s goal is to review the application within ten months after it accepts the application for filing, or, if the application relates to an unmet medical need in the treatment of a serious or life-threatening condition, six months after the FDA accepts the application for filing. The review process can be significantly extended by FDA requests for additional information or clarification.

The FDA’s Decision on an NDA or BLA

The FDA may issue an approval letter if it finds the application has adequate support for commercial marketing. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications. As a condition of NDA or BLA approval, the FDA may impose additional requirements, such as post-marketing studies and/or a Risk Evaluation and Mitigation Strategy, or REMS, to help ensure that the benefits of the drug outweigh the potential risks. A REMS can include medication guides, assessment plans, communication plans for healthcare professionals, and elements to assure safe use. The FDA may also issue a Complete Response Letter, which indicates that the review cycle of the application is complete but the application is not ready for approval. A Complete Response Letter may require additional clinical data and/or an additional pivotal Phase 3 clinical study(ies), and/or other significant, expensive and time-consuming requirements related to clinical studies, preclinical studies or manufacturing. If the conditions set forth in the Complete Response Letter are met, the FDA may approve the product for marketing.

Expedited Review and Accelerated Approval Programs

A sponsor may seek approval of its product candidate under programs designed to accelerate the FDA’s review and approval of NDAs and BLAs. For example, Fast Track Designation may be granted to a drug intended for treatment of a serious or life-threatening disease or condition and data demonstrate its potential to address unmet medical needs for the disease or condition. The key benefits of fast-track designation are the eligibility for priority review, rolling review (submission of portions of an application before the complete marketing application is submitted), and accelerated approval, if relevant criteria are met. The FDA may grant the NDA or BLA a priority review designation, which sets the target date for FDA action on the application at six months after the FDA accepts the application for filing. Priority review is granted where there is evidence that the proposed product would be a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious condition. Priority review designation does not change the scientific/medical standard for approval or the quality of evidence necessary to support approval.

The FDA may approve an NDA or BLA under the accelerated approval program if the drug treats a serious condition, provides a meaningful advantage over available therapies, and demonstrates an effect on either (1) a surrogate endpoint that is reasonably likely to predict clinical benefit, or (2) on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. Post-marketing studies or completion of ongoing studies after marketing approval are generally required to verify the drug’s clinical benefit in relationship to the surrogate endpoint or ultimate outcome in relationship to the clinical benefit. The FDA may require, as appropriate, that such studies be underway prior to approval or within a specific time period after the date of approval for a product that has been granted accelerated approval. The FDA also has authority for expedited procedures to withdraw approval of a product or indication that was initially approved under accelerated approval if the sponsor fails to conduct the required post-marketing studies or if such studies fail to verify the predicted clinical benefit. In addition, as a condition for accelerated approval, the FDA currently also requires pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.

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In addition, the Food and Drug Administration Safety and Innovation Act, or FDASIA, established the Breakthrough Therapy designation. A sponsor may seek FDA designation of its product candidate as a breakthrough therapy if the drug is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. If a drug is designated as a breakthrough therapy, the FDA will provide more intensive guidance on the drug development program and expedite its review.

Furthermore, the FDA has made available expedited programs to sponsors of regenerative medicine therapies that have been granted designation as a regenerative medicine advanced therapy, or RMAT. Regenerative medicine therapies include cell therapies, therapeutic tissue engineering products and human cell and tissue products. A sponsor may seek RMAT designation if its regenerative medicine product is intended to treat, modify, reverse, or cure a serious or life-threatening condition and preliminary clinical evidence indicates that the regenerative medicine therapy has the potential to address unmet medical needs for such condition. Advantages of the RMAT designation include early interactions with the FDA to discuss the development plan for the product candidate, including potential surrogate or intermediate endpoints, and eligibility for rolling and priority review. Products granted RMAT designation may also be eligible for accelerated approval on the basis of a surrogate or intermediate endpoint reasonably likely to predict long-term clinical benefit, or reliance upon data obtained from a meaningful number of sites, including through expansion to additional sites. RMAT-designated products that receive accelerated approval may, as appropriate, fulfill their post-approval requirements through the submission of clinical evidence, clinical studies, patient registries, or other sources of real-world evidence (such as electronic health records); through the collection of larger confirmatory data sets; or via post-approval monitoring of all patients treated with such therapy prior to approval of the therapy.

Orphan Designation and Exclusivity

Under the Orphan Drug Act, the FDA may grant orphan drug designation to drugs intended to treat a rare disease or condition that affects fewer than 200,000 individuals in the U.S., or if it affects more than 200,000 individuals in the U.S. and there is no reasonable expectation that the cost of developing and making the drug for this type of disease or condition will be recovered from sales in the U.S. Orphan drug designation must be requested before submitting an NDA or BLA. After the FDA grants orphan drug designation, the identity of the therapeutic agent and its potential orphan use are publicly disclosed by the FDA.

Orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical study costs, tax advantages, and user-fee waivers. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process. In addition, the first NDA or BLA applicant to receive orphan drug designation for a particular drug is entitled to orphan drug exclusivity, which means the FDA may not approve any other application to market the same drug for the same indication for a period of seven years in the U.S., except in limited circumstances. Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same disease or condition, or the same drug for a different disease or condition.

There is some uncertainty with respect to the FDA’s interpretation of the scope of orphan drug exclusivity. Historically, exclusivity was specific to the orphan indication for which the drug was approved. As a result, the scope of exclusivity was interpreted as preventing approval of a competing product. However, in 2021, the federal court in Catalyst Pharmaceuticals, Inc. v. Becerra, suggested that orphan drug exclusivity covers the full scope of the orphan-designated “disease or condition” regardless of whether a drug obtained approval for a narrower use.

Pediatric Studies and Exclusivity

NDAs and BLAs must contain data to assess the safety and effectiveness of an investigational new drug product for the claimed indications in all relevant pediatric populations in order to support dosing and administration for each pediatric subpopulation for which the drug is safe and effective. The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults or full or partial waivers if certain criteria are met. Pediatric development plans can be discussed with the FDA at any time, but usually occur any time between the end-of-Phase 2 meeting and submission of the NDA or BLA. Unless otherwise required by regulation, the requirements for pediatric data do not apply to any drug for an indication for which orphan designation has been granted.

Pediatric exclusivity is another type of non-patent exclusivity in the U.S. that may be granted if certain FDA requirements are met, such as FDA’s determination that information relating to the use of a new drug in the pediatric population may produce health benefits, and the applicant agrees to perform and report on FDA-requested studies within a certain time frame. Pediatric exclusivity adds a period of six months of exclusivity to the end of all existing marketing exclusivity and patents held by the sponsor for that active moiety. This is not a patent term extension, but it effectively extends the regulatory period during which the FDA cannot accept or approve another application relying on the NDA or BLA sponsor’s data.

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Biosimilars and Exclusivity

The Patient Protection and Affordable Care Act of 2010, or Affordable Care Act, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or BPCI Act, which created an abbreviated approval pathway for biological products shown to be similar to, or interchangeable with, an FDA-licensed reference biological product.

A reference biologic is granted twelve years of exclusivity from the time of first licensure of the reference product. The first biologic product submitted under the abbreviated approval pathway that is determined to be interchangeable with the reference product has exclusivity against other biologics submitted under the abbreviated approval pathway for the lesser of (i) one year after the first commercial marketing, (ii) eighteen months after approval if there is no legal challenge, (iii) eighteen months after the resolution in the applicant’s favor of a lawsuit challenging the biologics’ patents if an application has been submitted, or (iv) 42 months after the application has been approved if a lawsuit is ongoing within the 42-month period.

The Inflation Reduction Act of 2022, or the IRA, is intended to foster generic and biosimilar competition and to lower drug and biologic costs. The IRA provides the Centers for Medicare & Medicaid Services, or CMS, with significant new authorities. CMS is able to directly negotiate prescription drug prices and to cap out-of-pocket costs. Each year, CMS will select and negotiate a preset number of high-spend drugs and biologics covered under Medicare Parts B and D that lack generic or biosimilar competition. Price negotiations began in 2023. Effective from 2023, the IRA provides a new “inflation rebate” that covers Medicare patients and is intended to counter certain price increases in prescription drugs. The inflation rebate requires drug manufacturers to pay a rebate to the federal government if the price for a drug or biologic under Medicare Parts B or D increases faster than the rate of inflation. To support biosimilar competition, qualifying biosimilars may receive a Medicare Part B payment increase for a period of five years, beginning in October 2022. Separately, if a biologic drug for which no biosimilar exists delays a biosimilar’s market entry beyond two years, CMS will be authorized to subject the biologics manufacturer to price negotiations intended to ensure fair competition. Notwithstanding these provisions, the IRA’s impact on competition and commercialization remains largely uncertain.

Abbreviated New Drug Applications for Generic Drugs and New Chemical Entity Exclusivity

The Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Amendments, authorized the FDA to approve generic drugs that are bioequivalent (i.e. identical) to previously approved branded drugs. To obtain approval of a generic drug, an applicant must submit an abbreviated new drug application, or ANDA, to the FDA. In support of such applications, a generic manufacturer may rely on the preclinical and clinical testing conducted for a drug product previously approved under an NDA, known as the reference listed drug, or RLD.

Specifically, in order for an ANDA to be approved, the FDA must find that the generic version is bioequivalent to the RLD with respect to the active ingredients, the route of administration, the dosage form, quality and performance characteristics, the strength of the drug, and intended use.

The FDCA provides a period of five years of non-patent exclusivity for a new drug containing a new chemical entity. In cases where such exclusivity has been granted, an ANDA may not be filed with the FDA until the expiration of five years unless the submission is accompanied by a Paragraph IV certification, in which case the applicant may submit its application four years following the original product approval. The FDCA also provides for a period of three years of exclusivity if an NDA or supplement includes reports of one or more new clinical investigations, other than bioavailability or bioequivalence studies, that were conducted by or for the applicant and are essential to the approval of the application. This three-year exclusivity period often protects changes to a previously approved drug product, such as a new dosage form, route of administration, combination or indication.

When an ANDA applicant files its application with the FDA, it must certify, among other things, that the new product will not infringe the already approved product’s listed patents or that such patents are invalid or unenforceable, which is called a Paragraph IV certification. If the applicant does not challenge the listed patents or indicates that it is not seeking approval of a patented method of use, the ANDA application will not be approved until all the listed patents claiming the referenced product have expired. If the ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the ANDA has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days after the receipt of a Paragraph IV certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months after the receipt of the Paragraph IV notice, expiration of the patent, or a decision in the infringement case that is favorable to the ANDA applicant.

Section 505(b)(2) New Drug Applications

As an alternative path to FDA approval for modifications to formulations or uses of products previously approved by the FDA pursuant to an NDA, an applicant may submit an NDA under Section 505(b)(2) of the FDCA. Section 505(b)(2) was enacted as part of the Hatch-Waxman Amendments and permits the filing of an NDA where at least some of the information required for approval

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comes from studies not conducted by, or for, the applicant, and for which the applicant has not obtained a right of reference. If the Section 505(b)(2) applicant can establish that reliance on the FDA’s previous findings of safety and effectiveness is scientifically and legally appropriate, it may eliminate the need to conduct certain preclinical studies or clinical trials of the new product. The FDA may also require companies to perform additional bridging studies or measurements, including clinical trials, to support the change from the previously approved reference drug. The FDA may then approve the new drug candidate for all, or some, of the label indications for which the reference drug has been approved, as well as for any new indication sought by the Section 505(b)(2) applicant.

To the extent that a Section 505(b)(2) applicant is relying on studies conducted for an already approved product, the applicant is required to certify to the FDA concerning any patents listed for the approved product in the Orange Book to the same extent that an ANDA applicant would. As a result, approval of a Section 505(b)(2) NDA can be stalled until all the listed patents claiming the referenced product have expired, until any non-patent exclusivity (such as exclusivity for obtaining approval of a new chemical entity) listed in the Orange Book for the referenced product has expired and, in the case of a Paragraph IV certification and subsequent patent infringement suit, until the earlier of 30 months, settlement of the lawsuit, or a decision in the infringement case that is favorable to the Section 505(b)(2) applicant.

Patent Term Restoration

Some of our U.S. patents may be eligible for limited patent term extension under the Hatch-Waxman Amendments. The Hatch-Waxman Amendments permit a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process. However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date. The patent term restoration period is generally one-half the time between the effective date of an IND and the submission date of an NDA or BLA, plus the time between the submission date and the approval of that application. Only one patent applicable to an approved product is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent. The USPTO, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration. Thus, for each approved product, we may apply for restoration of patent term for one of our related owned or licensed patents to add patent life beyond the original expiration date, depending on the expected length of the clinical studies and other factors involved in the filing of the relevant NDA or BLA.

EU Regulation

In the EU and in Iceland, Norway and Liechtenstein, together the European Economic Area or EEA, after completion of all required clinical testing, pharmaceutical products may only be placed on the market after obtaining a Marketing Authorization, or MA. To obtain a MA, we must submit a marketing authorization application, or MAA. The content of the MAA is similar to that of an NDA or BLA filed in the U.S., with the exception of, among other things, country-specific document requirements.

Authorization Procedures

Medicines can be authorized by using, among other things, a centralized or decentralized procedure. The centralized authorization procedure results in a single marketing authorization issued by the European Commission, or EC, following the scientific assessment of the application by the European Medicines Agency, or EMA, that is valid across the EEA. The centralized procedure is compulsory for specific medicinal products, including medicines developed by means of certain biotechnological processes, products designated as orphan medicinal products, advanced therapy medicinal products, or ATMPs, and medicinal products with a new active substance indicated for the treatment of certain diseases (for instance, AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and viral diseases). Medicines that fall outside the mandatory scope of the centralized procedure have three routes to authorization: (i) they can be authorized under the centralized procedure if they concern a significant therapeutic, scientific or technical innovation, or if their authorization would be in the interest of public health; (ii) they can be authorized under a decentralized procedure where an applicant applies for simultaneous authorization in more than one EU country; or (iii) they can be authorized in a EU member state in accordance with that state’s national procedures and then be authorized in other EU countries by a procedure whereby the countries concerned agree to recognize the validity of the original, national marketing authorization (mutual recognition procedure).

All new MAAs must include a Risk Management Plan, or RMP, describing the risk management system that the Company will put in place and documenting measures to prevent or minimize the risks associated with the product. RMPs are continually modified and updated throughout the lifetime of the medicine as new information becomes available. We need to submit an updated RMP: (i) at the request of EMA or a national competent authority, or (ii) whenever the risk-management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit-risk profile or as a result of an important pharmacovigilance or risk-minimization milestone being reached. The regulatory authorities may also impose specific obligations as a condition of the MA. RMPs and Periodic Safety Update Reports, or PSURs, are routinely available to third parties requesting access, subject to limited redactions.

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Special rules apply in part for ATMPs. ATMPs comprise gene therapy products, somatic cell therapy products and tissue engineered products, which are genes, cells or tissues that have undergone substantial manipulation and that are administered to human beings in order to cure, diagnose or prevent diseases or regenerate, repair or replace a human tissue. Pursuant to the ATMP Regulation, the Committee on Advanced Therapies, or CAT, is responsible in conjunction with the CHMP for the evaluation of ATMPs. The CHMP and CAT are also responsible for providing guidelines on ATMPs. These guidelines provide additional guidance on the factors that the EMA will consider in relation to the development and evaluation of ATMPs and include, among other things, the preclinical studies required to characterize ATMPs. The manufacturing and control information that should be submitted in a MAA; and post-approval measures required to monitor patients and evaluate the long- term efficacy and potential adverse reactions of ATMPs. Although such guidelines are not legally binding, compliance with them is often necessary to gain and maintain approval for product candidates. In addition to the mandatory RMP, the holder of a MA for an ATMP must put in place and maintain a system to ensure that each individual product and its starting and raw materials, including all substances coming into contact with the cells or tissues it may contain, can be traced through the sourcing, manufacturing, packaging, storage, transport and delivery to the relevant healthcare institution where the product is used.

A Pediatric Investigation Plan, or PIP, and/or a request for waiver (for example, because the relevant disease or condition occurs only in adults) or deferral (for example, until enough information to demonstrate its effectiveness and safety in adults is available), is required for submission prior to submitting an MAA. A PIP describes, among other things, proposed pediatric studies and their timing relative to clinical studies in adults and an MAA must comply with the PIP to be validated.

MAA Review and Approval Timeframe and Accelerated Assessment

Under the centralized procedure in the EU, the Committee for Medicinal Products for Human Use, or CHMP, established at the EMA, is responsible for conducting the initial assessment of a drug. In principle, the maximum timeframe for the evaluation of an MAA by the CHMP is 210 days from receipt of a valid MAA. However, this timeline excludes clock stops, when additional written or oral information is to be provided by the applicant in response to questions asked by the CHMP, so the overall process typically takes a year or more. A favorable opinion on the application by the CHMP will typically result in the granting of the marketing authorization within 67 days of receipt of the opinion. Accelerated evaluation might be granted by the CHMP in exceptional cases, when a medicinal product is expected to be of a major public health interest, particularly from the point of view of therapeutic innovation. In this circumstance, and upon request by the applicant, the CHMP’s evaluation time frame is reduced to 150 days, excluding time taken by an applicant to respond to questions.

MA Validity Period

MAs have an initial duration of five years. After five years, the authorization may subsequently be renewed on the basis of a reevaluation of the risk-benefit balance. Once renewed, the MA is valid for an unlimited period unless the EC or the national competent authority decides, on justified grounds relating to pharmacovigilance, to proceed with only one additional five-year renewal. Applications for renewal must be made to the EMA at least nine months before the five-year period expires.

Conduct of Clinical Trials

Clinical trials are studies intended to discover or verify the effects of one or more investigational medicines. The regulation of clinical trials aims to promote the protection of the rights, safety and well-being of trial participants and the credibility of the results of clinical trials. Regardless of where they are conducted, all clinical trials included in applications for marketing authorization for human medicines in the EU or EEA must have been carried out in accordance with EU regulations (such as, among others, the Clinical Trials Regulation (Regulation (EU) No 536/2014) and the Clinical Trials Directive (EC) No 2001/20/EC). This means that clinical trials conducted in the EU or EEA have to comply with EU clinical trial legislation and that clinical trials conducted outside the EU or EEA have to comply with ethical principles equivalent to those set out in the EEA, including adhering to international good clinical practice and the Declaration of Helsinki.

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Exceptional Circumstances/Conditional Approval

Orphan drugs or drugs with unmet medical needs may be eligible for EU approval under exceptional circumstances or with conditional approval. Approval under exceptional circumstances is applicable to orphan products and is used when an applicant is unable to provide comprehensive data on the efficacy and safety under normal conditions of use because the indication for which the product is intended is encountered so rarely that the applicant cannot reasonably be expected to provide comprehensive evidence, when the present state of scientific knowledge does not allow comprehensive information to be provided, or when it is medically unethical to collect such information. A conditional MA is applicable to orphan medicinal products, medicinal products for seriously debilitating or life-threatening diseases, or medicinal products to be used in emergency situations in response to recognized public threats. Conditional MAs can be granted for medicinal products where, although comprehensive clinical data referring to the safety and efficacy of the medicinal product have not been supplied, a number of criteria are fulfilled: (i) the benefit/risk balance of the product is positive, (ii) it is likely that the applicant will be in a position to provide the comprehensive clinical data, (iii) unmet medical needs will be fulfilled by the grant of the MA and (iv) the benefit to public health of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required. Conditional MAs are valid for only one year and must be reviewed annually subject to certain specific obligations.

PRIME Program

PRIME is a program launched by the EMA to enhance support for the development of medicines that target an unmet medical need. The program focuses on medicines that may offer a major therapeutic advantage over existing treatments, or benefit patients without treatment options. These medicines are considered priority medicines by EMA. To be accepted for PRIME, a medicine has to show its potential to benefit patients with unmet medical needs based on early clinical data. Through PRIME, the EMA offers early and proactive support to medicine developers to optimize development plans and the generation of robust data on a medicine’s benefits and risks and enables accelerated assessment of medicines applications. PRIME eligibility does not change the standards for product approval, and there is no assurance that any such designation or eligibility will result in expedited review or approval.

Orphan Designation and Exclusivity

As in the U.S., we may apply for designation of a product as an orphan drug for the treatment of a specific indication in the EU before the application for marketing authorization is made. The EMA’s Committee for Orphan Medicinal Products, or COMP, grants orphan drug designation to promote the development of products that are intended for the diagnosis, prevention, or treatment of life-threatening or chronically debilitating conditions affecting not more than 5 in 10,000 persons in the EU Community and for which no satisfactory method of diagnosis, prevention, or treatment has been authorized (or the product would be a significant benefit to those affected). Additionally, designation is granted for products intended for the diagnosis, prevention, or treatment of a life-threatening, seriously debilitating, or serious and chronic condition when, without incentives, it is unlikely that sales of the drug in the EU would be sufficient to justify the necessary investment in developing the medicinal product. Orphan drug designation entitles a party to financial incentives such as reduction of fees or fee waivers and 10 years of market exclusivity is granted following medicinal product approval. This period may be reduced to six years if the orphan drug designation criteria are no longer met, including where it is shown that the product is sufficiently profitable not to justify maintenance of market exclusivity. The applicant will receive a fee reduction for the MAA if the orphan drug designation has been granted, but not if the designation is still pending at the time the marketing authorization is submitted, and sponsors must submit an annual report to EMA summarizing the status of development of the medicine. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.

New Chemical Entity Exclusivity

In the EU, new chemical entities, or NCEs, sometimes referred to as new active substances, qualify for eight years of data exclusivity upon the product’s first MA in the EU and an additional two years of market exclusivity. This data exclusivity, if granted, prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic (abbreviated) application for eight years, after which generic marketing authorization can be submitted, and the innovator’s data may be referenced, but not approved for two years. The overall ten-year period will be extended to a maximum of eleven years if, during the first eight of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies. Products may not be granted data exclusivity since there is no guarantee that a product will be considered by the EU’s regulatory authorities to include an NCE. Even if a compound is considered to be a NCE and the MA applicant is able to gain the prescribed period of data exclusivity, another company could market a version of the medicinal product if such company can complete a full MAA with its own complete database of pharmaceutical tests, preclinical studies and clinical trials and obtain MA of its product.

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Post-Approval Requirements

Drugs manufactured or distributed pursuant to regulatory approvals are subject to pervasive and continuing regulation by the regulatory authorities, including, among other things, requirements relating to formal commitments for post approval clinical trials and studies, manufacturing, recordkeeping, periodic reporting, product sampling and distribution, marketing, labeling, advertising and promotion and reporting of adverse experiences with the product. After approval, most changes to the approved product, such as adding new indications or other labeling claims are subject to prior regulatory authority review and approval.

Drug manufacturers are subject to periodic unannounced inspections by regulatory authorities and country or state agencies for compliance with GMP and other requirements. Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior regulatory approval before being implemented. Regulations also require investigation and correction of any deviations from GMP and impose reporting and documentation requirements upon us and any third-party manufacturers that we may decide to use. Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain compliance with GMP and other aspects of regulatory compliance.

Pharmaceutical Coverage, Pricing and Reimbursement

In the U.S. and markets in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend in part on the availability of coverage and reimbursement from third-party payors. Third-party payors include government authorities, managed care providers, private health insurers and other organizations. The process for determining whether a payor will provide coverage for a drug product may be separate from the process for setting the reimbursement rate that the payor will pay for the drug product. Third-party payors may limit coverage to specific drug products on an approved list, or formulary, which might not include all of the approved drugs for a particular indication. Moreover, a payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved. Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development.

In the EU, governments influence the price of pharmaceutical products through their pricing and reimbursement rules and control of national health care systems that fund a large part of the cost of those products to patients. Some jurisdictions operate positive and negative list systems under which products may only be marketed once a reimbursement price has been agreed to by the government. Other member states allow companies to fix their own prices for medicines, but monitor and control company profits, including volume-based arrangements, caps and reference pricing mechanisms. In addition, in some countries, cross-border imports from low-priced markets exert a commercial pressure on pricing within a country.

Other Healthcare, Privacy, and Cybersecurity Laws and Compliance Requirements

We are subject to various laws targeting, among other things, fraud and abuse in the healthcare industry, and privacy and protection of personal information, including health information. These laws may impact, among other things, our proposed sales, marketing, and education programs. The laws that may affect our ability to operate include:

•the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting or receiving renumeration in return for, and from knowingly and willfully offering or paying remuneration to induce, referrals of federal healthcare program patients and the purchase or recommendation of an item or service reimbursable under a federal healthcare program, such as the Medicare and Medicaid programs;

•federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented to Medicare, Medicaid, or other third-party payers, claims for payment that are false or fraudulent;

•federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented to Medicare, Medicaid, or other third-party payers, claims for payment that are false or fraudulent;

•the EU General Data Protection Regulation, or GDPR, and the U.K. General Data Protection Regulation, or UK GDPR, which apply to processing of personal data in the context of the activities of an entity established in the EEA/UK, and to processing by an entity not established in the EEA/UK where such processing is related to the offering of goods or services to individuals who are in the EEA/UK, or the monitoring of the behavior of individuals who are in the EEA/UK, and imposes requirements and limitations relating to the processing, storage, purpose of collection, accuracy, security, sharing and transfer of personal data outside the EEA/UK, in particular with respect to special categories of personal data like health data, and the notification of supervisory authorities about data breaches, accompanied by a strong sanctioning mechanism—in addition, EU member states may also impose additional requirements in relation to health, genetic and biometric data through their national implementing legislation;

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•the 21st Century Cures Act, or the Cures Act, which introduced a wide range of reforms, such as broadening the types of data required to support drug approval, extending protections for generic competition, accelerating approval of breakthrough therapies, expanding the orphan drug product program, requiring disclosures about compassionate care programs, and clarifying how manufacturers communicate about their products;

•the federal transparency laws, including the federal Physician Payment Sunshine Act, that requires drug manufacturers to disclose payments and other transfers of value provided to various healthcare professionals and teaching hospitals; and

•state and foreign law equivalents, or similar, of each of the above federal laws, such as transparency laws, anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payer, including commercial insurers, and privacy and security of health information laws, including comprehensive privacy and security laws in California.

Additional Regulation

The U.S. Foreign Corrupt Practices Act or FCPA, to which we are subject, prohibits corporations and individuals from engaging in certain activities to obtain or retain business or to influence a person working in an official capacity. It is illegal to pay, offer to pay or authorize the payment of anything of value to any foreign government official, government staff member, political party, or political candidate in an attempt to obtain or retain business or to otherwise influence a person working in an official capacity. Similar laws exist in other countries, such as the United Kingdom or in EU member states, that restrict improper payments to public and private parties. Many countries have laws prohibiting these types of payments within the respective country. In addition to these anti-corruption laws, we are subject to import and export control laws, tariffs, trade barriers, economic sanctions, and regulatory limitations on our ability to operate in certain foreign markets.

In addition, federal, state, and foreign government bodies and agencies have adopted, are considering adopting, or may adopt laws and regulations regarding the collection, use, storage and disclosure of personally identifiable information or other information treated as confidential obtained from consumers and individuals.

We are also subject to regulation under the Occupational Safety and Health Act, the Environmental Protection Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act and other present and potential federal, state, or local regulations. These and other laws govern our use, handling and disposal of various biological and chemical substances used in, and waste generated by, our operations. Complying with these requirements may have a significant impact on our capital expenditures and results of operations.

Customers

Our customers include collaboration partners, drug wholesalers, and retail pharmacy distributors. For the year ended December 31, 2023, more than half of our total revenues were earned from our collaboration partner KKC.

Human Capital

General Information

As of December 31, 2023, we had 1,276 total employees, of which 876 are in research and development and 400 are in sales, general, and administrative. Further, 1,089 employees are based in the U.S., including at our facilities in Novato, California, Brisbane, California, Cambridge, Massachusetts, and Woburn, Massachusetts, and 187 employees are based at our international locations. The majority of new employees hired during the year ended December 31, 2023 were to support and extend our clinical and preclinical pipeline, our in-house manufacturing capacities for our GTMF, as well as our commercialization activities, with hires in commercial, clinical development and operations, research, manufacturing, and general and administrative functions. We believe our relationship with our employees to be generally good. We have not experienced any material employment-related issues or interruptions of services due to labor disagreements and are not a party to any collective bargaining agreements.

We expect to continue to strategically add employees in 2024 with a focus on expanding our in-house manufacturing capacity in connection with maintaining and operating our gene therapy manufacturing facility, increasing expertise and bandwidth in clinical and preclinical research and development and commercialization activities and expanding our geographic reach in connection with the global launches of our approved products. We continually evaluate our business need and opportunity and balances in-house expertise and capacity with outsourced expertise and capacity. Currently, we outsource substantial clinical trial work to clinical research organizations and certain drug manufacturing to contract manufacturers.

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Workforce Safety and Employee Wellbeing

We maintain a safety culture grounded on the premise of eliminating workplace incidents, risks and hazards. Our health and safety management system includes several elements, such as incorporation of Global Environmental, Health, Safety and Sustainability (EHSS) standards, site-specific standard operating procedures, incident and safety observation reporting, hazard identification and risk assessments, job safety analyses, ergonomic assessments and industrial hygiene evaluations. We have adopted a flexible, hybrid working arrangement for our employees, which allows some of our employees to work remotely during certain days of the week. We provide our employees with wellness offerings to support their physical and mental health including our “Caring For U” program, a global reimbursement program offering employees up to $1,200 annually (in local currency) for wellness and caregiving activities.

Employee Retention and Engagement

The biotechnology industry is an extremely competitive labor market and we believe our company’s success depends on our ability to attract, develop, and retain key personnel. We invest in the growth and development of our employees through various training and development programs that build and strengthen employees’ leadership and professional skills, including leadership development programs for new leaders, six sigma certification, as well as a mentoring program. We also have a talent management framework and processes in place that includes regularly conducted activities such as performance management, succession, and workforce planning in order to support our employees in their growth and development and to provide learning opportunities. We offer on-demand career coaching services through an external network of professional executive coaches. We encourage all employees to have an individual development plan to identify focus areas for learning and growth.

To regularly assess and improve our employee retention and engagement, we conduct an engagement survey approximately every 18 months, with "pulse" surveys in between, the results of which are discussed with our board of directors, at all hands employee meetings and in individual functions. We take actions to address areas of employment concern and follow-up routinely to share with employees what we are doing.

Diversity, Equity, Inclusion and Belonging

We are committed to fostering a healthy, inclusive environment while nurturing a culture of belonging where all employees have equal opportunities. We strive to create an environment where everyone we work with, serve, and engage with feels valued, respected, and empowered.

As of December 31, 2023, of the eight members of our board of directors, three directors were women, three directors self-identified as racially or ethnically diverse, and one director self-identified as LGBTQ+. As of December 31, 2023, women represented 56% of our global workforce and 44% of our leadership positions at the Vice President level or above. As of December 31, 2023, 46% of our U.S. workforce that self-reported identified as racially or ethnically diverse. We have included questions in our engagement survey to measure employee perception of our inclusive culture, with the results from such survey on inclusion and diversity included in our corporate goals. Our business units review diversity data related to hiring, promotions, and retention on an ongoing basis in order to promote inclusivity and equal employment opportunities.

We have also established a Diversity, Equity, Inclusion and Belonging, or DEIB Action Team, comprised of employee representatives throughout our company. In 2023, we hosted offsite DEIB workshops and retreats that brought together members of our DEIB Action Team and the leaders of our Employee Resource Groups (ERGs). These sessions were designed to support team building, building our leadership skills, critically assessing, and enhancing our multi-year DEIB corporate roadmap, aligning our efforts, and executing the roadmap's action items. In our efforts to promote diversity and inclusion, we have also established or supported several internal ERGs, including UltraProud, LatinX, UltraAPAC, UltraMosaic, and Empower X Women in Biotech.

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Benefits and Compensation

We are dedicated to fostering a workplace environment that keeps our employees inspired, including providing a comprehensive benefits program that supports the health care, family, and financial needs of our employees. All of our full-time employees are eligible for cash bonuses and equity awards in addition to other benefits including comprehensive health insurance, life and disability insurance, 401(k) matching, paid time off for volunteering, wellness programs, and tuition reimbursement. We benchmark and tie compensation to market data as well as to an employee’s experience, function and performance. Our compensation structure includes performance-based elements, with the goal of recognizing and rewarding exceptional performance. We regularly review our compensation policies and practices in an effort to identify and address any disparities or inequities.

General Information

Our Internet website address is www.ultragenyx.com. No portion of our website, or any other website that may be referenced, is incorporated by reference into this Annual Report.

You are advised to read this Annual Report in conjunction with other reports and documents that we file from time to time with the Securities and Exchange Commission, or the SEC. In particular, please read our definitive proxy statements, our Annual Reports on Form 10-K, our Quarterly Reports on Form 10-Q and any Current Reports on Form 8-K that we may file from time to time. The SEC maintains information for electronic filers (including Ultragenyx) at its website at www.sec.gov. We make our annual reports on Form 10-K, our quarterly reports on Form 10-Q, and our current reports on Form 8-K, and amendments to those reports, available on our internet website, free of charge, as soon as reasonably practicable after such material is electronically filed with, or furnished to, the SEC.

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Item 1A. Risk Factors

Investing in our common stock involves a high degree of risk. You should carefully consider the following material risks, together with all the other information in this Annual Report, including our financial statements and notes thereto, before deciding to invest in our common stock. The risks and uncertainties described below are not the only ones we face. Additional risk and uncertainties not presently known to us or that we presently deem less significant may also impair our business operations. If any of the following risks actually materialize, our operating results, financial condition, and liquidity could be materially adversely affected. As a result, the trading price of our common stock could decline and you could lose part or all of your investment. Our company’s business, financial condition and operating results can be affected by a number of factors, whether currently known or unknown, including but not limited to those described below, any one or more of which could, directly or indirectly, cause our actual financial condition and operating results to vary materially from past, or from anticipated future, financial condition and operating results. Any of these factors, in whole or in part, could materially and adversely affect our business, prospects, financial condition, operating results and stock price.

Because of the following factors, as well as other factors affecting our financial condition and operating results, past financial performance should not be considered to be a reliable indicator of future performance, and investors should not use historical trends to anticipate results or trends in future periods.

Risk Factor Summary

•We have a history of operating losses and anticipate that we will continue to incur losses for the foreseeable future.

•We have limited experience in generating revenue from product sales.

•We may need to raise additional capital to fund our activities.

•Clinical drug development is a lengthy, complex, and expensive process with uncertain outcomes.

•We may experience delays in commercialization of our products and other adverse effects if we do not achieve our projected development goals in the time frames we announce and expect.

•We may experience difficulty in enrolling patients.

•The regulatory approval processes of the FDA and comparable foreign authorities are lengthy and inherently unpredictable.

•Fast Track Product, Breakthrough Therapy, Priority Review or RMAT designations by the FDA, and analogous designations by the EMA, for our product candidates may not lead to faster development or approval.

•Our product candidates may cause undesirable or serious side effects.

•We face a multitude of manufacturing risks, particularly with respect to our gene therapy and mRNA product candidates.

•Our products remain subject to regulatory scrutiny even if we obtain regulatory approval.

•Product liability lawsuits against us could cause us to incur substantial liabilities.

•We may not realize the full commercial potential of our product candidates if we are unable to source and develop effective biomarkers.

•We rely on third parties to conduct our nonclinical and clinical studies and perform other tasks for us.

•We are dependent on KKC for the clinical and commercial supply of Crysvita for all major markets and for the development and commercialization of Crysvita in certain major markets.

•We rely on third parties to manufacture our products and product candidates.

•The loss of, or failure to supply by, any of any of our single-source suppliers for our drug substance and drug product could adversely affect our business.

•The actions of distributors and specialty pharmacies could affect our ability to sell or market products profitably.

•Our revenue may be adversely affected if the market opportunities for our products and product candidates are smaller than expected.

•Our competitors may develop therapies that are similar, more advanced, or more effective than ours.

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•We may not successfully manage expansion of our company, including building an integrated commercial organization.

•After the transition of our commercialization responsibilities for Crysvita in the U.S. and Canada, the success of Crysvita in those territories is dependent on the effectiveness of KKC’s commercialization efforts.

•Commercial success of our products depends on the degree of market acceptance.

•We face uncertainty related to insurance coverage and reimbursement status of our newly approved products.

•If we, or our third-party partners, are unable to maintain effective proprietary rights for our products or product candidates, we may not be able to compete effectively.

•Claims of intellectual property infringement may prevent or delay our development and commercialization efforts.

•We may not be successful in obtaining or maintaining necessary rights to our product candidates through acquisitions and in-licenses.

•We may face competition from biosimilars of our biologics product and product candidates or from generic versions of our small-molecule product and product candidates, which may result in a material decline in sales of affected products.

•We could lose license rights that are important to our business if we fail to comply with our obligations in the agreements under which we license intellectual property and other rights from third parties.

•We may become involved in lawsuits to protect or enforce our patents or the patents of our licensors, or be subject to claims that challenge the inventorship or ownership of our patents.

•Changes to patent laws in the U.S. and other jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our products.

•We may not be able to protect our intellectual property rights throughout the world.

•We have limited experience as a company operating our own manufacturing facility.

•Our success depends in part on our ability to retain our President and Chief Executive Officer and other qualified personnel.

•Our revenue may be impacted if we fail to obtain or maintain orphan drug exclusivity for our products.

•Our operating results may be adversely impacted if our intangible assets become impaired.

•We may not be successful in identifying, licensing, developing, or commercializing additional product candidates.

•We may fail to comply with laws and regulations or changes in laws and regulations could adversely affect our business.

•We are exposed to risks related to international expansion of our business outside of the U.S.

•Our business may be adversely affected in the event of computer system failures or security breaches.

•We or our third-party partners may be adversely affected by earthquakes or other serious natural disasters.

•We may incur various costs and expenses and risks related to acquisition of companies or products or strategic transactions.

•The market price of our common stock is highly volatile.

•Future sales and issuances of our common stock could dilute the percentage ownership of our current stockholders and result in a decline in stock price.

•Provisions in our amended and restated certificate of incorporation and by-laws, as well as provisions of Delaware law, could make it more difficult for a third party to acquire us or increase the cost of acquiring us or could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.

•We face general risks related to our ability to maintain effective internal controls over financial reporting, additional tax liabilities related to our operations, our ability to use our net operating loss carryforwards, costs of litigation, stockholder activism and increased scrutiny regarding our ESG practices and disclosures.

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Risks Related to Our Financial Condition and Capital Requirements

We have a history of operating losses and anticipate that we will continue to incur losses for the foreseeable future.

We are a biopharmaceutical company with a history of operating losses, and anticipate continuing to incur operating losses for the foreseeable future. Biopharmaceutical product development is a highly speculative undertaking and involves a substantial degree of risk. We have devoted substantially all of our financial resources to identifying, acquiring, and developing our products and product candidates, including conducting clinical studies, developing manufacturing processes, manufacturing product candidates for clinical studies, and providing selling, general and administrative support for these operations. The amount of our future net losses will depend, in part, on non-recurring events, the success of our commercialization efforts, and the rate of our future expenditures. We anticipate that our expenses will increase substantially if and as we:

•continue our research and nonclinical and clinical development of our product candidates;

•expand the scope of our current clinical studies for our product candidates;

•advance our programs into more expensive clinical studies;

•initiate additional nonclinical, clinical, or other studies for our product candidates;

•pursue preclinical and clinical development for additional indications for existing products and product candidates;

•change or add additional manufacturers or suppliers;

•expand upon our manufacturing-related facilities and capabilities, particularly as we continue to ramp-up operations at our GMP gene therapy manufacturing facility;

•seek regulatory and marketing approvals for our product candidates that successfully complete clinical studies;

•continue to establish Medical Affairs field teams to initiate relevant disease education;

•continue to establish a marketing and distribution infrastructure and field force to commercialize our products and any product candidates for which we may obtain marketing approval;

•continue to manage our international subsidiaries and establish new ones;

•continue to operate as a public company and comply with legal, accounting and other regulatory requirements;

•seek to identify, assess, license, acquire, and/or develop other product candidates, technologies, and/or businesses;

•make milestone or other payments under any license or other agreements;

•seek to maintain, protect, and expand our intellectual property portfolio;

•seek to attract and retain skilled personnel;

•create additional infrastructure, including facilities and systems, to support the growth of our operations, our product development, and our commercialization efforts; and

•experience any delays or encounter issues with any of the above, including, but not limited to, failed studies, complex results, safety issues, inspection outcomes, or other regulatory challenges that require longer follow-up of existing studies, additional major studies, or additional supportive studies in order to pursue marketing approval.

The net losses we incur may fluctuate significantly from quarter to quarter and year to year, such that a period-to-period comparison of our results of operations may not be a good indication of our future performance.

We have limited experience in generating revenue from product sales.

Our ability to generate significant revenue from product sales depends on our ability, alone or with strategic collaboration partners, to successfully commercialize our products and to complete the development of, and obtain the regulatory and marketing approvals necessary to commercialize, our product candidates. Our ability to generate substantial future revenue from product sales, including named patient sales, depends heavily on our success in many areas, including, but not limited to:

•obtaining regulatory and marketing approvals with broad indications for product candidates for which we complete clinical studies;

•developing a sustainable and scalable manufacturing process for our products and any approved product candidates and establishing and maintaining supply and manufacturing relationships with third parties that can conduct the processes

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and provide adequate (in amount and quality) product supply to support market demand for our products and product candidates, if approved;

•launching and commercializing our products and product candidates for which we obtain regulatory and marketing approval, either directly or with a collaborator or distributor;

•obtaining market acceptance of our products and product candidates as viable treatment options;

•obtaining adequate market share, reimbursement and pricing for our products and product candidates;

•our ability to sell our products and product candidates on a named patient basis or through an equivalent mechanism and the amount of revenue generated from such sales;

•our ability to find patients so they can be diagnosed and begin receiving treatment;

•addressing any competing technological and market developments;

•negotiating favorable terms, including commercial rights, in any collaboration, licensing, or other arrangements into which we may enter, any amendments thereto or extensions thereof;

•maintaining, protecting, and expanding our portfolio of intellectual property rights, including patents, trade secrets, and know-how; and

•attracting, hiring, and retaining qualified personnel.

If the number of our addressable rare disease patients is not as significant as we estimate, the indication approved by regulatory authorities is narrower than we expect, or the reasonably accepted population for treatment is narrowed by competition, physician choice, or treatment guidelines, or any other reasons, we may not generate significant revenue from sales of our products, even if they receive regulatory approval.

We may need to raise additional capital to fund our activities. Such additional financing may not be available on acceptable terms, if at all. Failure to obtain this necessary capital when needed may force us to delay, limit, or terminate our product development efforts or other activities.

As of December 31, 2023, our available cash, cash equivalents, and marketable debt securities were $777.1 million. We expect we will need additional capital to continue to commercialize our products, and to develop and obtain regulatory approval for, and to commercialize, all of our product candidates. In addition, our operating plans may change as a result of many factors that may currently be unknown to us, and we may need to seek additional funds sooner than planned. Our future funding requirements will depend on many factors, including but not limited to:

•the scope, rate of progress, results, and cost of our clinical studies, nonclinical testing, and other related activities;

•the cost of manufacturing clinical and commercial supplies of our products and product candidates;

•the cost of creating additional infrastructure, including facilities and systems, such as systems in our GMP gene therapy manufacturing facility;

•the cost of operating and maintaining our gene therapy manufacturing facility;

•the number and characteristics of the product candidates that we pursue;

•the cost, timing, and outcomes of regulatory approvals;

•the cost and timing of establishing and operating our international subsidiaries;

•the cost and timing of establishing and operating field forces, marketing, and distribution capabilities;

•the cost and timing of other activities needed to commercialize our products; and

•the terms and timing of any collaborative, licensing, acquisition, and other arrangements that we may establish, including any required milestone, royalty, and reimbursements or other payments thereunder.

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Any additional fundraising efforts may divert our management’s attention from their day-to-day activities, which can adversely affect our ability to develop our product candidates and commercialize our products. In addition, we cannot guarantee that future financing will be available in sufficient amounts or on terms acceptable to us, if at all, particularly in light of the current macroeconomic conditions, including the general economic slowdown and potential recessionary environment. The terms of any financing may adversely affect the holdings or the rights of our stockholders and the issuance of additional securities by us, whether equity or debt, or the possibility of such issuance, may cause the market price of our shares to decline. The sale of additional equity or convertible securities would dilute all of our stockholders. If we incur debt, it could result in increased fixed payment obligations and we may be required to agree to certain restrictive covenants, such as limitations on our ability to incur additional debt, limitations on our ability to acquire, sell, or license intellectual property rights, and other operating restrictions that could adversely impact our ability to conduct our business. We have in the past sought and may in the future seek funds through a sale of future royalty payments similar to our transactions with Royalty Pharma and OMERS or through collaborative partnerships, strategic alliances, and licensing or other arrangements, such as our transaction with Daiichi Sankyo Co., Ltd., or Daiichi Sankyo, and we may be required to relinquish rights to some of our technologies or product candidates, future revenue streams, research programs, and other product candidates or otherwise agree to terms unfavorable to us, any of which may have a material adverse effect on our business, operating results, and prospects. Even if we believe we have sufficient funds for our current or future operating plans, we may seek additional capital if market conditions are favorable or if we have specific strategic considerations.

In addition, we may not be able to access a portion of our existing cash, cash equivalents and investments due to market conditions. If banks or financial institutions enter receivership or become insolvent in the future, similar to what occurred at Silicon Valley Bank in March 2023, or if there is a concern that they may do so in response to financial conditions affecting the banking system and financial markets, our ability to access our existing cash, cash equivalents and investments may be threatened and the value of our investments may be significantly impaired.

If we are unable to access our existing cash, cash equivalents and investments and/or are unable to obtain funding on a timely basis, or at all, we may be required to significantly curtail, delay, or discontinue one or more of our research or development programs or the commercialization of our products and any approved product candidates or be unable to expand our operations or otherwise capitalize on our business opportunities, as desired, which could materially affect our business, financial condition, and results of operations.

Risks Related to the Discovery and Development of Our Product Candidates

Clinical drug development involves a lengthy, complex, and expensive process with uncertain outcomes and the potential for substantial delays, and the results of earlier studies may not be predictive of future study results.

Before obtaining marketing approval from regulatory authorities for the sale of our product candidates, we must conduct extensive clinical studies to demonstrate the safety and efficacy of the product candidates in humans. Clinical testing is expensive, complex, time consuming, and uncertain as to outcome. We cannot guarantee that any clinical studies will be conducted as planned or completed on schedule, if at all. We have also had difficulties in recruiting clinical site investigators and clinical staff for our studies, and may continue to experience such difficulties. Additionally, a failure of one or more clinical studies can occur at any stage of testing, and our future clinical studies may not be successful. Product candidates that have shown promising results in early-stage clinical studies may still suffer significant setbacks or fail in subsequent clinical studies. The safety or efficacy results generated to date in clinical studies do not ensure that later clinical studies will demonstrate similar results. Further, we have reported and expect to continue to report preliminary or interim data from our clinical trials. Preliminary or interim data from our clinical trials are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and/or more patient data become available. Such data may show initial evidence of clinical benefit, but as patients continue to be assessed and more patient data become available, there is a risk that any therapeutic effects are no longer durable in patients and/or decrease over time or cease entirely. As a result, preliminary or interim data should be considered carefully and with caution until the final data are available. Results from investigator-sponsored studies or compassionate-use studies may not be confirmed in company-sponsored studies or may negatively impact the prospects for our programs. Additionally, given the nature of the rare diseases we are seeking to treat, we often devise newly-defined endpoints to be tested in our studies, which can lead to subjectivity in interpreting study results and could result in regulatory agencies not agreeing with the validity of our endpoints, or our interpretation of the clinical data, and therefore delaying or denying approval. Given the illness of the patients in our studies and the nature of their rare diseases, we have also been required to or have chosen to conduct certain studies on an open-label basis. We have in the past, and may in the future elect to review interim clinical data at multiple time points during the studies, which could introduce bias into the study results and potentially result in denial of approval.

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In the biopharmaceutical industry, there is a high failure rate for drugs and biologics proceeding through clinical studies, and product candidates in later stages of clinical studies may fail to show the desired safety and efficacy despite having progressed through nonclinical studies and initial clinical studies. A number of companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical studies due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier studies.

Scenarios that can prevent successful or timely completion of clinical development include but are not limited to:

•delays or failures in generating sufficient preclinical, toxicology, or other in vivo or in vitro data to support the initiation or continuation of human clinical studies or filings for regulatory approval;

•failure to demonstrate a starting dose for our product candidates in the clinic that might be reasonably expected to result in a clinical benefit;

•delays or failures in developing gene therapy, messenger RNA, or mRNA, DNA, small interfering RNA, or siRNA, or other novel and complex product candidates, which are expensive and difficult to develop and manufacture;

•delays resulting from a shutdown, or uncertainty surrounding the potential for future shutdowns of the U.S. government, including the FDA;

•delays or failures in reaching a consensus with regulatory agencies on study design;

•delays in reaching agreement on acceptable terms with contract research organizations, or CROs, clinical study sites, and other clinical trial-related vendors;

•failure or delays in obtaining required regulatory agency approval and/or IRB or EC approval at each clinical study site or in certain countries;

•failure to correctly design clinical studies which may result in those studies failing to meet their endpoints or the expectations of regulatory agencies;

•changes in clinical study design or development strategy resulting in delays related to obtaining approvals from IRBs or ECs and/or regulatory agencies to proceed with clinical studies;

•imposition of a clinical hold by regulatory agencies after review of an IND application or amendment, another equivalent application or amendment, or an inspection of our clinical study operations or study sites;

•delays in recruiting suitable patients to participate in our clinical studies;

•difficulty collaborating with patient groups and investigators;

•failure by our CROs, other third parties, or us to adhere to clinical study requirements;

•failure to perform in accordance with the FDA’s and/or ICH’s good clinical practices requirements or applicable regulatory guidelines in other countries;

•delays in patients’ completion of studies or their returns for post-treatment follow-up;

•patients dropping out of a study;

•adverse events associated with the product candidate occurring that are viewed to outweigh its potential benefits;

•changes in regulatory requirements and guidance that require amending or submitting new clinical protocols;

•greater than anticipated costs associated with clinical studies of our drug candidates, including as a result of inflation;

•clinical studies of our drug candidates producing negative or inconclusive results, which may result in us deciding, or regulators requiring us, to conduct additional clinical or nonclinical studies or to abandon drug development programs;

•competing clinical studies of potential alternative product candidates or investigator-sponsored studies of our product candidates; and

•delays in manufacturing, testing, releasing, validating, or importing/exporting sufficient stable quantities of our product candidates for use in clinical studies or the inability to do any of the foregoing.

Any inability to successfully complete nonclinical and clinical development could result in additional costs to us or negatively impact our ability to generate revenue. In addition, if we make manufacturing or formulation changes to our product candidates, we may need to conduct additional toxicology, comparability or other studies to bridge our modified product candidates to earlier versions. Clinical study delays could also shorten any periods during which our products have commercial exclusivity and may allow our competitors to bring products to market before we do, which could negatively impact our ability to obtain orphan exclusivity and to successfully commercialize our product candidates and may harm our business and results of operations.

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If we do not achieve our projected development goals in the time frames we announce and expect, the commercialization of our products may be delayed and the credibility of our management may be adversely affected and, as a result, our stock price may decline.

For planning purposes, we estimate the timing of the accomplishment of various scientific, clinical, regulatory, and other product development goals, which we sometimes refer to as milestones. These milestones may include the commencement or completion of scientific studies and clinical trials, the timing of patient dosing, the timing, type or clarity of data from clinical trials, the submission or acceptance of regulatory filings, and the potential approval of such regulatory filings. We periodically make public announcements about the expected timing of some of these milestones. All of these milestones are based on a variety of assumptions, but the actual timing of these milestones can vary dramatically from our estimates. If we do not meet these publicly announced milestones, the commercialization of our products may be delayed and the credibility of our management may be adversely affected and, as a result, our stock price may decline.

We may find it difficult to identify and enroll patients in our clinical studies due to a variety of factors, including the limited number of patients who have the diseases for which our product candidates are being studied and other unforeseen events. Difficulty in enrolling patients could delay or prevent clinical studies of our product candidates.

Identifying and qualifying patients to participate in clinical studies of our product candidates is critical to our success. The timing of our clinical studies depends in part on the speed at which we can recruit patients to participate in testing our product candidates, and we may experience delays in our clinical studies if we encounter difficulties in enrollment.

Each of the conditions for which we plan to evaluate our current product candidates is a rare genetic disease. Accordingly, there are limited patient pools from which to draw for clinical studies. For example, we estimate that approximately 6,000 patients worldwide suffer from GSDIa, for which DTX401 is being studied, and these all may not be treatable if they are immune to the AAV viral vector.

In addition to the rarity of these diseases, the eligibility criteria of our clinical studies will further limit the pool of available study participants as we will require patients to have specific characteristics that we can measure or to assure their disease is either severe enough or not too advanced to include them in a study. The process of finding and diagnosing patients is costly and time-consuming, especially since the rare diseases we are studying are commonly underdiagnosed. We also may not be able to identify, recruit, and enroll a sufficient number of appropriate patients to complete our clinical studies because of demographic criteria for prospective patients, the perceived risks and benefits of the product candidate under study, the proximity and availability of clinical study sites for prospective patients, and the patient referral practices of physicians. The availability and efficacy of competing therapies and clinical studies can also adversely impact enrollment. If patients are unwilling to participate in our studies for any reason (such as drug-related side effects), the timeline for and our success in recruiting patients, conducting studies, and obtaining regulatory approval of potential products may be delayed or impaired, the commercial prospects of our product candidates will be harmed, and our ability to generate product sales from any of these product candidates could be delayed or prevented. Delays in completing our clinical studies will increase our costs, slow down our product candidate development and approval process, and jeopardize our ability to commence product sales and generate revenue.

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The regulatory approval processes of the FDA and comparable foreign authorities are lengthy, time consuming, and inherently unpredictable. Even if we achieve positive results in our pre-clinical and clinical studies, if we are ultimately unable to obtain timely regulatory approval for our product candidates, our business will be substantially harmed.

Our future success is dependent on our ability to successfully commercialize our products and develop, obtain regulatory approval for, and then successfully commercialize one or more product candidates. We are not permitted to market or promote any of our product candidates before we receive regulatory approval from the FDA or comparable foreign regulatory authorities. We have only obtained regulatory approval for three products that we have developed, and it is possible that none of our existing product candidates or any product candidates we may seek to develop in the future will ever obtain regulatory approval. Further, as the clinical trial requirements of regulatory authorities and the criteria these regulators use to determine the safety and efficacy of a product candidate vary substantially according to the type, complexity, novelty and intended use and market of the product candidates, the regulatory approval process for novel product candidates, such as our gene therapy product candidates, can be more expensive and take longer than for other product candidates, leading to fewer product approvals. To date, very few gene therapy products have received regulatory approval in the U.S. or Europe. The regulatory framework and oversight over development of gene therapy products has evolved and may continue to evolve in the future. Within the FDA, the Center for Biologics Evaluation and Research, or CBER, regulates gene therapy products. Within the CBER, the review of gene therapy and related products is consolidated in the Office of Cellular, Tissue and Gene Therapies, and the FDA has established the Cellular, Tissue and Gene Therapies Advisory Committee to advise CBER on its reviews. The CBER works closely with the National Institutes of Health, or NIH. The FDA and the NIH have published guidance with respect to the development and submission of gene therapy protocols. For example, in January 2020, the FDA issued final guidance to set forth the framework for the development, review and approval of gene therapies. The final guidance pertains to the development of gene therapies for the treatment of specific disease categories, including rare diseases, and to manufacturing and long-term follow up issues relevant to gene therapy, among other topics. At the same time the FDA issued guidance describing the FDA’s approach for determining whether two gene therapy products were the same or different for the purpose of assessing orphan drug exclusivity. Within the European Medicines Agency, or EMA, special rules apply to gene therapy and related products as they are considered advanced therapy medicinal products, or ATMPs. Pursuant to the ATMP Regulation, the Committee on Advanced Therapies, or CAT, is responsible in conjunction with the Committee for Medicinal Products for Human Use, or CHMP, for the evaluation of ATMPs. The CHMP and CAT are also responsible for providing guidelines on ATMPs. These guidelines provide additional guidance on the factors that the EMA will consider in relation to the development and evaluation of ATMPs and include, among other things, the preclinical studies required to characterize ATMPs. The manufacturing and control information that should be submitted in a MAA; and post-approval measures required to monitor patients and evaluate the long-term efficacy and potential adverse reactions of ATMPs. Although such guidelines are not legally binding, compliance with them is often necessary to gain and maintain approval for product candidates. In addition to the mandatory risk-management plan, or RMP, the holder of a marketing authorization for an ATMP must put in place and maintain a system to ensure that each individual product and its starting and raw materials, including all substances coming into contact with the cells or tissues it may contain, can be traced through the sourcing, manufacturing, packaging, storage, transport, and delivery to the relevant healthcare institution where the product is used.

To obtain regulatory approval in the U.S. and other jurisdictions, we must comply with numerous and varying requirements regarding safety, efficacy, chemistry, manufacturing and controls, clinical studies (including good clinical practices), commercial sales, pricing, and distribution of our product candidates, as described above in “Item 1. Business – Government Regulation”. Even if we are successful in obtaining approval in one jurisdiction, we cannot ensure that we will obtain approval in any other jurisdictions. In addition, approval policies, regulations, positions of the regulatory agencies on study design and/or endpoints, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development, which may cause delays in the approval or the decision not to approve an application. Communications with the regulatory agencies during the approval process are also unpredictable; favorable communications early in the process do not ensure that approval will be obtained and unfavorable communications early on do not guarantee that approval will be denied. Applications for our product candidates could fail to receive regulatory approval, or could be delayed in receiving regulatory approval, for many reasons, including but not limited to the following:

•regulatory authorities may disagree with the design, implementation, or conduct of our clinical studies;

•regulatory authorities may change their guidance or requirements for a development program for a product candidate;

•the population studied in the clinical program may not be sufficiently broad or representative to assure efficacy and safety in the full population for which we seek approval;

•regulatory authorities may disagree with our interpretation of data from nonclinical studies or clinical studies;

•the data collected from clinical studies of our product candidates may not be sufficient to support the submission of an NDA, or biologics license application, or BLA, or other submission or to obtain regulatory approval;

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•we may be unable to demonstrate to regulatory authorities that a product candidate’s risk-benefit ratio for its proposed indication is acceptable;

•regulatory authorities may fail to approve the manufacturing processes, test procedures and specifications, or facilities used to manufacture our clinical and commercial supplies;

•the U.S. government may be shut down, which could delay the FDA;

•the FDA may be delayed in responding to our applications or submissions due to competing priorities or limited resources, including as a result of the lack of FDA funding or personnel;

•failure of our nonclinical or clinical development to comply with an agreed upon Pediatric Investigational Plan, or PIP, which details the designs and completion timelines for nonclinical and clinical studies and is a condition of marketing authorization in the EU; and

•the approval policies or regulations of regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.

Furthermore, the disease states we are evaluating often do not have clear regulatory paths for approval and/or do not have validated outcome measures. In these circumstances, we work closely with the regulatory authorities to define the approval path and may have to qualify outcome measures as part of our development programs. Additionally, many of the disease states we are targeting are highly heterogeneous in nature, which may impact our ability to determine the treatment benefit of our potential therapies.

This lengthy and uncertain approval process, as well as the unpredictability of the clinical and nonclinical studies, may result in our failure to obtain regulatory approval to market any of our product candidates, or delayed regulatory approval.

Fast Track, Breakthrough Therapy, Priority Review, or Regenerative Medicine Advanced Therapy, or RMAT, designations by the FDA, or access to the Priority Medicine scheme, or PRIME, by the EMA, for our product candidates, if granted, may not lead to faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.

As described in “Item 1. Business – Government Regulation”, we seek Fast Track, Breakthrough Therapy designation, RMAT designation, PRIME scheme access or Priority Review designation for our product candidates if supported by the results of clinical trials. Designation as a Fast Track product, Breakthrough Therapy, RMAT, PRIME, or Priority Review product is within the discretion of the relevant regulatory agency. Accordingly, even if we believe one of our product candidates meets the criteria for designation as a Fast Track product, Breakthrough Therapy, RMAT, PRIME, or Priority Review product, the agency may disagree and instead determine not to make such designation. The receipt of such a designation for a product candidate also may not result in a faster development process, review or approval compared to drugs considered for approval under conventional regulatory procedures and does not assure that the product will ultimately be approved by the regulatory authority. In addition, regarding Fast Track products and Breakthrough Therapies, the FDA may later decide that the products no longer meet the conditions for qualification as either a Fast Track product, RMAT, or a Breakthrough Therapy or, for Priority Review products, decide that period for FDA review or approval will not be shortened. Furthermore, with respect to PRIME designation by the EMA, PRIME eligibility does not change the standards for product approval, and there is no assurance that any such designation or eligibility will result in expedited review or approval.

The FDA Rare Pediatric Disease Priority Review Voucher Program, or PRV Voucher Program, awards Priority Review Vouchers, or PRVs, to sponsors of rare pediatric product applications that meet certain criteria. Under the program, a company that receives an approval for a product for a rare pediatric disease (as determined by the applicable regulations) may qualify for a PRV that can be redeemed to receive Priority Review of a subsequent marketing application for a different product. PRVs may also be sold by the company to third parties. We received PRVs under the PRV Voucher Program in connection with the approval of Mepsevii and Crysvita in 2018 and subsequently sold these two PRVs to third parties for an average amount of $105.3 million for each PRV. The current PRV Voucher Program is scheduled to sunset such that the FDA may only award a PRV for a product application if a company receives the rare pediatric disease designation from the FDA for the product candidate by September 30, 2024, and the FDA will cease awarding PRVs after September 30, 2026. Extension of the current PRV Voucher Program is subject to approval by Congress and it is currently uncertain whether the program will be extended. If our qualifying product candidates are approved by the FDA after the current approval deadlines, we will not be eligible to receive additional PRVs for our product candidates and accordingly, we would be unable to use such PRV for Priority Review for another one of our programs or to sell such PRV, which sale has the potential to generate significant proceeds.

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Our product candidates may cause undesirable side effects or have other properties that could delay or prevent their regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any.

Undesirable side effects caused by our product candidates could cause us or regulatory authorities to interrupt, delay, or halt clinical studies or further development, and could result in a more restrictive label, the delay or denial of regulatory approval by the FDA or other comparable foreign authorities, or a Risk Evaluation and Mitigation Strategy, or REMS, plan, which could include a medication guide outlining the risks of such side effects for distribution to patients, restricted distribution, a communication plan for healthcare providers, and/or other elements to assure safe use. Our product candidates are in development and the safety profile has not been established. Further, as one of the goals of Phase 1 and/or 2 clinical trials is to identify the highest dose of treatment that can be safely provided to study participants, adverse side effects, including serious adverse effects, have occurred in certain studies as a result of changes to the dosing regimen during such studies and may occur in future studies. Results of our studies or investigator-sponsored trials could reveal a high and unacceptable severity and prevalence of these or other side effects. In such an event, our studies could be suspended or terminated, and the FDA or comparable foreign regulatory authorities could order us to cease further development of or deny or withdraw approval of our product candidates for any or all targeted indications.

Additionally, notwithstanding our prior or future regulatory approvals for our product candidates, if we or others later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result, including but not limited to:

•regulatory authorities may withdraw approvals of such product;

•regulatory authorities may require additional warnings on the product’s label or restrict the product’s approved use;

•we may be required to create a REMS plan;

•patients and physicians may elect not to use our products, or reimbursement authorities may elect not to reimburse for them; and

•our reputation may suffer.

Any of these events could prevent us from achieving or maintaining market acceptance of the particular product candidate, if approved.

Serious adverse events in clinical trials involving gene therapy product candidates may damage public perception of the safety of our product candidates, increase government regulation, and adversely affect our ability to obtain regulatory approvals for our product candidates or conduct our business.

Gene therapy remains a novel technology. Public perception may be influenced by claims that gene therapy is unsafe, and gene therapy may not gain the acceptance of the public or the medical community. For example, certain gene therapy trials using AAV8 vectors (although at significantly higher doses than those used in our gene therapy product candidates) and other vectors led to several well-publicized adverse events, including cases of leukemia and death. The risk of cancer or death remains a concern for gene therapy and we cannot assure you that it will not occur in any of our planned or future clinical studies. In addition, there is the potential risk of delayed adverse events following exposure to gene therapy products due to persistent biological activity of the genetic material or other components of products used to carry the genetic material. Serious adverse events in our clinical trials, or other clinical trials involving gene therapy products, particularly AAV gene therapy products such as candidates based on the same capsid serotypes as our product candidates, or occurring during use of our competitors’ products, even if not ultimately attributable to the relevant product candidates, and the resulting publicity, could result in increased government regulation, unfavorable public perception, potential regulatory delays in the testing or approval of our gene therapy product candidates, stricter labeling requirements for those gene therapy product candidates that are approved and a decrease in demand for any such gene therapy product candidates.

Gene therapy and mRNA, DNA and siRNA product candidates are novel, complex, expensive and difficult to manufacture. We could experience manufacturing problems that result in delays in developing and commercializing these programs or otherwise harm our business.

The manufacturing process used to produce our gene therapy, mRNA, DNA and siRNA product candidates is novel, complex, and has not been validated for commercial use. Several factors could cause production interruptions, including equipment malfunctions, malfunctions of internal information technology systems, regulatory inspections, facility contamination, raw material shortages or contamination, natural disasters, geopolitical instability, disruption in utility services, human error or disruptions in the operations of our suppliers. Further, given that cGMP gene therapy, mRNA, DNA and siRNA manufacturing is a nascent industry, there are a small number of CMOs with the experience necessary to manufacture our gene therapy product candidates and we may

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have difficulty finding or maintaining relationships with such CMOs or hiring experts for internal manufacturing and accordingly, our production capacity may be limited.

Our gene therapy, mRNA, DNA and siRNA product candidates require processing steps that are more complex than those required for most small molecule drugs. Moreover, unlike small molecules, the physical and chemical properties of a biologic such as gene therapy, mRNA, DNA and siRNA product candidates generally cannot be fully characterized. As a result, assays of the finished product candidate may not be sufficient to ensure that the product candidate is consistent from lot to lot or will perform in the intended manner. Accordingly, we employ multiple steps to control the manufacturing process to assure that the process works reproducibly, and the product candidate is made strictly and consistently in compliance with the process. Problems with the manufacturing process, even minor deviations from the normal process, could result in product defects or manufacturing failures that result in lot failures, noncompliance with regulatory requirements, product recalls, product liability claims or insufficient inventory. We may encounter problems achieving adequate quantities and quality of clinical-grade materials that meet FDA, the EMA or other applicable standards or specifications with consistent and acceptable production yields and costs.

In addition, FDA, the EMA and other foreign regulatory authorities may require us to submit samples of any lot of any approved product together with the protocols showing the results of applicable tests at any time. Under some circumstances, FDA, the EMA or other foreign regulatory authorities may require that we not distribute a lot until the agency authorizes its release. Slight deviations in the manufacturing process, including those affecting quality attributes and stability, may result in unacceptable changes in the product that could result in lot failures or product recalls. Lot failures or product recalls could cause us to delay product launches or clinical trials, which could be costly to us and otherwise harm our business, financial condition, results of operations and prospects.

Even if we obtain regulatory approval for our product candidates, our products remain subject to regulatory scrutiny.

Our products and any product candidates that are approved in the future remain subject to ongoing regulatory requirements for manufacturing, labeling, packaging, storage, distribution, advertising, promotion, sampling, record-keeping, conduct of post-marketing studies, and submission of safety, efficacy, and other post-market information, including both federal and state requirements in the U.S. and requirements of comparable foreign regulatory authorities, as described above in “Item 1. Business – Government Regulation.”

Manufacturers and manufacturers’ facilities are required to comply with extensive FDA, and comparable foreign regulatory authority, requirements, including ensuring that quality control and manufacturing procedures conform to Good Manufacturing Practices, or GMP, regulations. As such, we and our contract manufacturers are subject to continual review and inspection to assess compliance with GMP and adherence to commitments made in any NDA, BLA, MAA, or other comparable application for approval in another jurisdiction. Although we are not involved in the day-to-day operations of our contract manufacturers, we are ultimately responsible for ensuring that our products are manufactured in accordance with GMP regulations. Regulatory authorities may, at any time, audit or inspect a manufacturing facility involved with the preparation of our products, product candidates or the associated quality systems for compliance with the regulations applicable to the activities being conducted. Due to the complexity of the processes used to manufacture our products and product candidates, we or any of our collaborators or contract manufacturers may be unable to comply with GMP regulations in a cost-effective manner and may be unable to initially or continue to pass a federal, national or international regulatory inspection. If we, our collaborators, such as KKC or Regeneron, or any of our third-party manufacturers fail to maintain regulatory compliance, the FDA or other applicable regulatory authority can impose regulatory sanctions including, among other things, warning or untitled letters, fines, unanticipated compliance expenses, the temporary or permanent suspension of a clinical study or commercial sales, recalls or seizures of product or the temporary or permanent closure of a facility or withdrawal of product approval, enforcement actions and criminal or civil prosecution. If supply from one approved manufacturer is interrupted due to failure to maintain regulatory compliance, an alternative manufacturer would need to be qualified through an NDA or BLA supplement or MAA variation, or equivalent foreign regulatory filing, which could result in delays in product supply. The regulatory agencies may also require additional studies if a new manufacturer, material, testing method or standard is relied upon for commercial production. Switching manufacturers, materials, test methods or standards may involve substantial costs and may result in a delay in our desired clinical and commercial timelines. Accordingly, we and others with whom we work are required continue to expend time, money, and effort in all areas of regulatory compliance, including manufacturing, production, and quality control.

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Any regulatory approvals that we receive for our product candidates may be subject to limitations on the approved indicated uses for which the product may be marketed or other conditions of approval, or contain requirements for potentially costly post-marketing testing, including Phase 4 clinical studies, and surveillance to monitor the safety and efficacy of the product candidate. We could also be asked to conduct post-marketing clinical studies to verify the safety and efficacy of our products in general or in specific patient subsets. If original marketing approval was obtained via the accelerated approval or conditional marketing authorization pathways, we would be required to conduct a successful post-marketing clinical study to confirm clinical benefit for our products. An unsuccessful post-marketing study or failure to complete such a study could result in the withdrawal of marketing approval. We will be required to report certain adverse events and manufacturing problems, if any, to the FDA and comparable foreign regulatory authorities. The holder of an approved NDA, BLA, MAA, or other comparable application must submit new or supplemental applications and obtain approval for certain changes to the approved product, product labeling, or manufacturing process.

If we fail to comply with applicable regulatory requirements, or there are safety or efficacy problems with a product, a regulatory agency or enforcement authority may, among other things:

•issue warning or notice of violation letters;

•impose civil or criminal penalties;

•suspend or withdraw regulatory approval;

•suspend any of our ongoing clinical studies;

•refuse to approve pending applications or supplements to approved applications submitted by us;

•impose restrictions on our operations, including closing our contract manufacturers’ facilities;

•seize or detain products, or require a product recall; or

•require entry into a consent decree.

Any government investigation of alleged violations of law could require us to expend significant time and resources in response, and could generate negative publicity. Any failure to comply with ongoing regulatory requirements may significantly and adversely affect our ability to commercialize and generate revenue from our products. If regulatory sanctions are applied or if regulatory approval is withdrawn, the value of our company and our operating results will be adversely affected.

Product liability lawsuits against us could cause us to incur substantial liabilities and could limit commercialization of our approved products or product candidates.

We face an inherent risk of product liability exposure related to the testing of our approved products and product candidates in human clinical trials, as well as in connection with commercialization of our current and future products. If we cannot successfully defend ourselves against claims that any of our approved products or product candidates caused injuries, we could incur substantial liabilities. There can be no assurance that our product liability insurance, which provides coverage in the amount of $15.0 million in the aggregate, will be sufficient in light of our current or planned clinical programs. We may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability, or losses may exceed the amount of insurance that we carry. A product liability claim or series of claims brought against us could cause our stock price to decline and, if judgments exceed our insurance coverage, could adversely affect our results of operations and business. In addition, regardless of merit or eventual outcome, product liability claims may result in impairment of our business reputation, withdrawal of clinical study participants, costs due to related litigation, distraction of management’s attention from our primary business, initiation of investigations by regulators, substantial monetary awards to patients or other claimants, the inability to commercialize our product candidates, and decreased demand for our product candidates, if approved for commercial sale.

If we are unable to identify, source, and develop effective biomarkers, or our collaborators are unable to successfully develop and commercialize companion diagnostics for our product candidates, or experience significant delays in doing so, we may not realize the full commercial potential of our product candidates.

We are developing companion diagnostic tests to identify the right patients for certain of our product candidates and to monitor response to treatment. In certain cases, diagnostic tests may need to be developed as companion diagnostics and regulatory approval obtained in order to commercialize some product candidates. We currently use and expect to continue to use biomarkers to identify the right patients for certain of our product candidates. We may also need to develop predictive biomarkers in the future. We can offer no assurances that any current or future potential biomarker will in fact prove predictive, be reliably measured, or be accepted as a measure of efficacy by the FDA or other regulatory authorities. In addition, our success may depend, in part, on the development and commercialization of companion diagnostics. We also expect the FDA will require the development

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and regulatory approval of a companion diagnostic assay as a condition to approval of our gene therapy product candidates. There has been limited success to date industrywide in developing and commercializing these types of companion diagnostics. Development and manufacturing of companion diagnostics is complex and there are limited manufacturers with the necessary expertise and capability. Even if we are able to successfully develop companion diagnostics, we may not be able to manufacture the companion diagnostics at a cost or in quantities or on timelines necessary for use with our product candidates. To be successful, we need to address a number of scientific, technical and logistical challenges. We are currently working with a third party to develop companion diagnostics; however, we have little experience in the development and commercialization of diagnostics and may not ultimately be successful in developing and commercializing appropriate diagnostics to pair with any of our product candidates that receive marketing approval. We rely on third parties for the automation, characterization and validation, of our bioanalytical assays, companion diagnostics and the manufacture of its critical reagents.

Companion diagnostics are subject to regulation by the FDA and similar regulatory authorities outside the U.S. as medical devices and require regulatory clearance or approval prior to commercialization. In the U.S., companion diagnostics are cleared or approved through FDA’s 510(k) premarket notification or premarket approval, or PMA, process. Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted 510(k) premarket notification, PMA or equivalent application types in jurisdictions outside the U.S., may cause delays in the approval, clearance or rejection of an application. Given our limited experience in developing and commercializing diagnostics, we expect to rely in part or in whole on third parties for companion diagnostic design and commercialization. We and our collaborators may encounter difficulties in developing and obtaining approval or clearance for the companion diagnostics, including issues relating to selectivity/specificity, analytical validation, reproducibility, or clinical validation. Any delay or failure by us or our collaborators to develop or obtain regulatory approval of the companion diagnostics could delay or prevent approval of our product candidates.

Risks Related to our Reliance on Third Parties

We rely on third parties to conduct our nonclinical and clinical studies and perform other tasks for us. If these third parties do not successfully carry out their contractual duties, meet expected deadlines, or comply with regulatory requirements, we may be exposed to sub-optimal quality and reputational harm, we may not be able to obtain regulatory approval for or commercialize our product candidates, and our business could be substantially harmed.

We have relied upon and plan to continue to rely upon third parties, including CROs, collaborative partners, and independent investigators to analyze, collect, monitor, and manage data for our ongoing nonclinical and clinical programs. We rely on third parties for execution of our nonclinical and clinical studies, and for estimates regarding costs and efforts completed, and we control only certain aspects of their activities. We and our CROs and other vendors and partners are required to comply with GMP, GCP, and GLP, which are regulations and guidelines enforced by the FDA, the Competent Authorities of the Member States of the European Economic Area, and comparable foreign regulatory authorities for all of our product candidates in development. Regulatory authorities enforce these regulations through periodic inspections of study sponsors, principal investigators, study sites, and other contractors. If we or any of our CROs or other vendors and partners, including the sites at which clinical studies are conducted, fail to comply with applicable regulations, the data generated in our nonclinical and clinical studies may be deemed unreliable and the FDA, EMA, or comparable foreign regulatory authorities may deny approval and/or require us to perform additional nonclinical and clinical studies before approving our marketing applications, which would delay the approval process. We cannot make assurances that upon inspection by a given regulatory authority, such regulatory authority will determine that any of our clinical studies comply with GCP regulations or that nonclinical studies comply with GLP regulations. In addition, our clinical studies must be conducted with products produced under GMP regulations. If the regulatory authorities determine that we have failed to comply with GLP, GMP, or GCP regulations, they may deny approval of our product candidates and/or we may be required to repeat clinical or nonclinical studies, which would delay the regulatory approval process.

Our CROs and other vendors and partners are not our employees and we cannot control whether or not they devote sufficient time and resources to our on-going nonclinical and clinical programs, except for the limited remedies available to us under our agreements with such third parties. If our vendors and partners do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced, or if the quality or accuracy of the data they obtain is compromised due to the failure to adhere to our protocols, regulatory requirements, or for other reasons, our clinical studies may be extended, delayed, or terminated, and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates. CROs and other vendors and partners have also generated higher costs than anticipated as a result of changes in scope of work or otherwise. As a result, the commercial prospects for our product candidates could be harmed, our costs could increase, and our ability to generate revenue could be delayed.

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If any of our relationships with these third parties terminate, we may not be able to enter into arrangements with alternative vendors or do so on commercially reasonable terms. Switching or adding additional vendors involves additional cost and requires management time and focus. In addition, there is a natural transition period when a new vendor commences work. As a result, delays may occur, which can materially impact our ability to meet our desired clinical development timelines. Our efforts to manage our relationships with our vendors and partners can provide no assurance that we will not encounter similar challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition, and business prospects.

We also rely on third parties in other ways, including efforts to support patient diagnosis and identify patients, to assist our finance and legal departments, and to provide other resources for our business. Use of these third parties could expose us to sub-optimal quality, missed deadlines, and non-compliance with applicable laws, all of which could result in reputational harm to us and negatively affect our business.

We are dependent on KKC for the clinical and commercial supply of Crysvita for all major markets and for the development and commercialization of Crysvita in certain major markets, and KKC’s failure to provide an adequate supply of Crysvita or to commercialize Crysvita in those markets could result in a material adverse effect on our business and operating results.

Under our agreement with KKC, KKC has the sole right to commercialize Crysvita in Europe and, at certain specified times, in the U.S., Canada, and Turkey, subject to certain rights retained. Our partnership with KKC may not be successful, and we may not realize the expected benefits from such partnership, due to a number of important factors, including but not limited to the following:

•KKC has no obligation under our agreement to use diligent efforts to commercialize Crysvita in Europe. The timing and amount of any royalty payments that are made by KKC based on sales of Crysvita in Europe will depend on, among other things, the efforts, allocation of resources, and successful commercialization of Crysvita by KKC in Europe;

•the timing and amount of any payments we may receive under our agreement with KKC will depend on, among other things, the efforts, allocation of resources, and successful commercialization of Crysvita by KKC in the U.S. and Canada under our agreement;

•KKC may change the focus of its commercialization efforts or pursue higher priority programs;

•KKC may make decisions regarding the indications for our product candidates in countries where it has the sole right to commercialize the product candidates that limit commercialization efforts in those countries or in countries where we have the right to commercialize our product candidates;

•KKC may make decisions regarding market access and pricing in countries where it has the sole right to commercialize our product candidates which can negatively impact our commercialization efforts in countries where we have the right to commercialize our product candidates;

•KKC may fail to manufacture or supply sufficient drug product of Crysvita in compliance with applicable laws and regulations or otherwise for our development and clinical use or commercial use, which could result in program delays or lost revenue;

•KKC may elect to develop and commercialize Crysvita indications with a larger market than XLH and at a lower price, thereby reducing the profit margin on sales of Crysvita for any orphan indications, including XLH;

•if KKC were to breach or terminate the agreement with us, we would no longer have any rights to develop or commercialize Crysvita or such rights would be limited to non-terminated countries;

•KKC may terminate its agreement with us, adversely affecting our potential revenue from licensed products; and

•the timing and amounts of expense reimbursement that we may receive are uncertain, and the total expenses for which we are obligated to reimburse KKC may be greater than anticipated.

We rely on third parties to manufacture our products and our product candidates and we are subject to a multitude of manufacturing risks, any of which could substantially increase our costs and limit the supply of our product and product candidates.

As we currently lack the resources and the full capability to manufacture all of our products and product candidates on a clinical or commercial scale, we rely on third parties to manufacture our products and product candidates. Although we oversee the contract manufacturers, we cannot control the manufacturing process of, and are substantially dependent on, our contract manufacturing partners for compliance with the regulatory requirements. See “- Even if we obtain regulatory approval for our product candidates, our products remain subject to regulatory scrutiny” risk factor above. Further, we depend on our manufacturers

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to purchase from third-party suppliers the materials necessary to produce our products and product candidates. There are a limited number of suppliers for raw materials that we use to manufacture our drugs, placebos, or active controls, and there may be a need to identify alternate suppliers to prevent or mitigate a possible disruption of the manufacture of the materials necessary to produce our products and product candidates for our clinical studies, and, if approved, ultimately for commercial sale. We also do not have any control over the process or timing of the acquisition of these raw materials by our manufacturers. We may also experience interruptions in supply of product if the product or raw material components fail to meet our quality control standards or the quality control standards of our suppliers.

Further, manufacturers that produce our products and product candidates may not have experience producing our products and product candidates at commercial levels and may not produce our products and product candidates at the cost, quality, quantities, locations, and timing needed to support profitable commercialization. We have not yet secured manufacturing capabilities for commercial quantities of all of our product candidates and may be unable to negotiate binding agreements with manufacturers to support our commercialization activities on commercially reasonable terms. Even if our third-party product manufacturers develop acceptable manufacturing processes that provide the necessary quantities of our products and product candidates in a compliant and timely manner, the cost to us for the supply of our products and product candidates manufactured by such third parties may be high and could limit our profitability. For instance, KKC is our sole supplier of commercial quantities of Crysvita. The supply price to us for commercial sales of Crysvita in Latin America and the transfer price for commercial sales of the product in the U.S. and Canada was 35% of net sales through December 31, 2022 and 30% thereafter, which is higher than the typical cost of sales for companies focused on rare diseases.

The process of manufacturing our products and product candidates is complex, highly regulated, and subject to several risks, including but not limited to those listed below.

•The process of manufacturing our products and product candidates is extremely susceptible to product loss due to contamination, equipment failure or improper installation or operation of equipment, or vendor or operator error. Even minor deviations from normal manufacturing processes for our products and any of our product candidates could result in reduced production yields, product defects, and other supply disruptions. If microbial, viral, or other contaminations are discovered in our products and product candidates or in the manufacturing facilities in which our products and product candidates are made, such manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination.

•The manufacturing facilities in which our products and product candidates are made could be adversely affected by equipment failures, labor shortages, raw material shortages, natural disasters, power failures, actual or threatened public health emergencies, and numerous other factors.

Any adverse developments affecting manufacturing operations for our products and product candidates may result in shipment delays, inventory shortages, lot failures, withdrawals or recalls, or other interruptions in the supply of our products and product candidates. Due to their stage of development, small volume requirements, and infrequency of batch production runs, we carry limited amounts of safety stock for our products and product candidates. We have, and may in the future, be required to take inventory write-offs and incur other charges and expenses for products and product candidates that fail to meet specifications, undertake costly remediation efforts, or seek more costly manufacturing alternatives.

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The drug substance and drug product for our products and most of our product candidates are currently acquired from single-source suppliers. The loss of these suppliers, or their failure to supply us with the necessary drug substance or drug product, could materially and adversely affect our business.

We acquire most of the drug substances and drug products for our products and product candidates from single sources. If any single source supplier breaches an agreement with us, or terminates the agreement in response to an alleged breach by us or otherwise becomes unable or unwilling to fulfill its supply obligations, we would not be able to manufacture and distribute the product or product candidate until a qualified alternative supplier is identified, which could significantly impair our ability to commercialize such product or delay the development of such product candidate. For example, the drug substance and drug product for Crysvita and Evkeeza are made, respectively, by KKC pursuant to a license and collaboration agreement and Regeneron pursuant to a supply agreement. The drug substance and drug product for Mepsevii are currently manufactured by Rentschler under a commercial supply and services agreement, accompanying purchase orders, and other agreements. Pharmaceutical-grade drug substance for Dojolvi is manufactured by IOI Oleo pursuant to a supply agreement, and the drug product for Dojolvi is prepared by Haupt Pharma AG, pursuant to a master services agreement. Single source suppliers are also used for our gene therapy programs. Haupt Pharma closed its Wolfrathshausen, Germany site, which produces the Dojolvi drug product, at the end of 2023. As such, we are in the process of qualifying and conducting transfer activities to an alternative supplier. We cannot provide assurances that qualifying alternate sources, if available at all, for the Dojolvi drug product or for any of our other drug substances and drug products, and establishing relationships with such sources would not result in significant expense, supply disruptions or delay in the commercialization of our products or the development of our product candidates. Additionally, we may not be able to enter into supply arrangements with an alternative supplier on commercially reasonable terms or at all. The terms of any new agreement may also be less favorable or more costly than the terms we have with our current supplier. A delay in the commercialization of our products or the development of our product candidates or having to enter into a new agreement with a different third-party on less favorable terms than we have with our current suppliers could have a material adverse impact upon on our business.

The actions of distributors and specialty pharmacies could affect our ability to sell or market products profitably. Fluctuations in buying or distribution patterns by such distributors and specialty pharmacies could adversely affect our revenues, financial condition, or results of operations.

We rely on commercial distributors and specialty pharmacies for a considerable portion of our product sales and such sales are concentrated within a small number of distributors and specialty pharmacies. The financial failure of any of these parties could adversely affect our revenues, financial condition or results of operations. Our revenues, financial condition or results of operations may also be affected by fluctuations in buying or distribution patterns of such distributors and specialty pharmacies. These fluctuations may result from seasonality, pricing, wholesaler inventory objectives, or other factors.

Risks Related to Commercialization of Our Products and Product Candidates

If the market opportunities for our products and product candidates are smaller than we believe they are, our revenue may be adversely affected, and our business may suffer. Because the target patient populations of our products and product candidates are small, and the addressable patient population potentially even smaller, we must be able to successfully identify patients and acquire a significant market share to achieve profitability and growth.

We focus our research and product development on treatments for rare and ultrarare genetic diseases. Given the small number of patients who have the diseases that we are targeting, it is critical to our ability to grow and become profitable that we continue to successfully identify patients with these rare and ultrarare genetic diseases. Some of our current products or clinical programs may also be most appropriate for patients with more severe forms of their disease. For instance, while adults make up the majority of the XLH patients, they often have less severe disease that may reduce the penetration of Crysvita in the adult population relative to the pediatric population. Given the overall rarity of the diseases we target, it is difficult to project the prevalence of the more severe forms, or the other subsets of patients that may be most suitable to address with our products and product candidates, which may further limit the addressable patient population to a small subset. Our projections of both the number of people who have these diseases, as well as the subset of people with these diseases who have the potential to benefit from treatment with our products and product candidates, are based on our beliefs and estimates. These estimates have been derived from a variety of sources, including the scientific literature, surveys of clinics, patient foundations, or market research, and may prove to be incorrect. Further, new studies may change the estimated incidence or prevalence of these diseases. The number of patients may turn out to be lower than expected. The effort to identify patients with diseases we seek to treat is in early stages, and we cannot accurately predict the number of patients for whom treatment might be possible. Additionally, the potentially addressable patient population for each of our products and product candidates may be limited or may not be amenable to treatment with our products and product candidates, and new patients may become increasingly difficult to identify or access. Further, even if we obtain significant market share for our products and product candidates, because the potential target populations are very small, we may never become or remain profitable nor generate sufficient revenue growth to sustain our business.

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We face intense competition and rapid technological change and the possibility that our competitors may develop therapies that are similar, more advanced, or more effective than ours, which may adversely affect our financial condition and our ability to successfully commercialize our product candidates.

The biotechnology and pharmaceutical industries are intensely competitive and subject to rapid and significant technological change. We are currently aware of various existing treatments that may compete with our products and product candidates. See “Item 1. Business – Competition” above.

We have competitors both in the U.S. and internationally, including major multinational pharmaceutical companies, specialty pharmaceutical companies, biotechnology companies, startups, academic research institutions, government agencies, and public and private research institutions. Many of our competitors have substantially greater financial, technical, and other resources, such as larger research and development staff and experienced marketing and manufacturing organizations. Additional mergers and acquisitions in the biotechnology and pharmaceutical industries can often result in even more resources being concentrated in our competitors. As a result, these companies may obtain regulatory approval more rapidly than we are able to and may be more effective in selling and marketing their products as well. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies. Competition may increase further as a result of advances in the commercial applicability of technologies and greater availability of capital for investment in these industries. Our competitors may succeed in developing, acquiring, or licensing on an exclusive basis, products that are more effective or less costly than any product candidate that we may develop, or achieve earlier patent protection, regulatory approval, product commercialization, and market penetration than we do. Additionally, technologies developed by our competitors may render our potential products and product candidates uneconomical or obsolete, and we may not be successful in marketing our products and product candidates against competitors.

We may not be able to effectively manage the expansion of our organization, including building an integrated commercial organization. If we are unable to expand our existing commercial infrastructure or enter into agreements with third parties to market and sell our products and product candidates, as needed, we may be unable to increase our revenue.

We expect to need additional managerial, operational, marketing, financial, legal, and other resources to support our development and commercialization plans and strategies. In order to successfully commercialize our products as well as any additional products that may result from our development programs or that we acquire or license from third parties, we are expanding our commercial infrastructure in, Europe, Latin America and the Asia-Pacific region. This infrastructure consists of both office-based as well as field teams with technical expertise, and will be expanded as we approach the potential approval dates of additional products that result from our development programs. Our management may need to divert a disproportionate amount of its attention away from our day-to-day activities and devote a substantial amount of time to managing these growth activities. We may not be able to effectively manage the expansion of our operations, which may result in weaknesses in our infrastructure, operational mistakes, loss of business opportunities, loss of employees, and reduced productivity among remaining employees. Our expected growth could require significant capital expenditures and may divert financial resources from other projects, such as the development of additional product candidates. If our management is unable to effectively manage our growth, our expenses may increase more than expected, our ability to generate and/or grow revenue could be reduced, and we may not be able to implement our business strategy. Our future financial performance and our ability to commercialize product candidates and compete effectively will depend, in part, on our ability to effectively manage any future growth.

We, as a company, have limited, recent experience selling and marketing our product and only some of our employees have prior experience promoting other similar products while employed at other companies. As we increase the number and range of our commercialized products, we may experience additional complexities in our sales process and strategy and may encounter difficulties in allocating sufficient resources to sales and marketing of certain products. Further, as we launch additional products or as demand for our products change, our initial estimate of the size of the required field force may be materially more or less than the size of the field force actually required to effectively commercialize our product candidates. As such, we may be required to hire larger teams to adequately support the commercialization of our products and product candidates or we may incur excess costs in an effort to optimize the hiring of commercial personnel. With respect to certain geographical markets, we may enter into collaborations with other entities to utilize their local marketing and distribution capabilities, but we may be unable to enter into such agreements on favorable terms, if at all. If our future collaborators do not commit sufficient resources to commercialize our future products, if any, and we are unable to develop the necessary marketing capabilities on our own, we will be unable to generate sufficient product sales to sustain our business. We face competition from companies that currently have extensive and well-funded marketing and sales operations. Without a large internal team or the support of a third party to perform key commercial functions, we may be unable to compete successfully against these more established companies.

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Our exclusive rights to promote Crysvita in the U.S. and Canada transitioned back to KKC and the success of Crysvita in those territories are dependent on the effectiveness of KKC’s commercialization efforts.

Pursuant to the terms of our collaboration and license agreement with KKC, or the collaboration agreement, we had the sole right to promote Crysvita in the U.S. and Canada, or the profit-share territory, for a specified period of time, with KKC increasingly participating in the promotion of the product until the transition date of April 2023. At the transition date, commercialization responsibilities for Crysvita in the profit-share territory transitioned to KKC, and KKC assumed responsibility for the commercialization of the product in the territory. After the transition date, the commercial success of Crysvita in the profit-share territory depends on, among other things, the efforts and allocation of resources of KKC, which we do not control. Failure by KKC to successfully market and sell Crysvita in the United States could have an adverse effect on our financial results.

The commercial success of any current or future product will depend upon the degree of market acceptance by physicians, patients, third-party payors, and others in the medical community.

Even with the requisite approvals from the FDA and comparable foreign regulatory authorities, the commercial success of our current and future products will depend in part on the medical community, patients, and payors accepting our current and future products as medically useful, cost-effective, and safe. Any product that we bring to the market may not gain market acceptance by physicians, patients, payors, and others in the medical community. The degree of market acceptance of any of our current and future products will depend on a number of factors, including:

•the efficacy of the product as demonstrated in clinical studies and potential advantages over competing treatments;

•the prevalence and severity of any side effects, including any limitations or warnings contained in a product’s approved labeling;

•the clinical indications for which approval is granted;

•relative convenience and ease of administration;

•the cost of treatment, particularly in relation to competing treatments;

•the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;

•the effectiveness of our field forces and marketing efforts;

•the strength of marketing and distribution support and timing of market introduction of competitive products;

•publicity concerning our products or competing products and treatments; and

•sufficient third-party insurance coverage and reimbursement.

Even if a potential product displays a favorable efficacy and safety profile in nonclinical and clinical studies, market acceptance of the product will not be fully known until after it is launched. Our efforts to educate the medical community and payors on the benefits of the product candidates require significant resources and may never be successful. If our current and future products fail to achieve an adequate level of acceptance by physicians, patients, payors, and others in the medical community, we will not be able to generate sufficient revenue to become or remain profitable.

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The insurance coverage and reimbursement status of newly approved products is uncertain. Failure to obtain or maintain adequate coverage and reimbursement for new or current products could limit our ability to market those products and decrease our ability to generate revenue.

Our target patient populations are small, and accordingly the pricing, coverage, and reimbursement of our products and product candidates, if approved, must be adequate to support our commercial infrastructure. Our per-patient prices must be sufficient to recover our development and manufacturing costs and potentially achieve profitability. We expect the cost of a single administration of gene therapy products, such as those we are developing, to be substantial, when and if they achieve regulatory approval. Accordingly, the availability and adequacy of coverage and reimbursement by governmental and private payors are essential for most patients to afford expensive treatments such as ours, assuming approval. Sales of our products and product candidates, if approved, will depend substantially, both domestically and abroad, on the extent to which their costs will be paid for by health maintenance, managed care, pharmacy benefit, and similar healthcare management organizations, or reimbursed by government authorities, private health insurers, and other payors. If coverage and reimbursement are not available, are available only to limited levels, or are not available on a timely basis, we may not be able to successfully commercialize our products and product candidates, if approved. For example, deteriorating economic conditions and political instability in certain Latin American countries and in Turkey continue to cause us to experience significant delays in receiving approval for reimbursement for our products and consequently impact our product commercialization timelines in such regions. Even if coverage is provided, the approved reimbursement amount may not be high enough to allow us to establish or maintain pricing sufficient to sustain our overall enterprise. In addition, we do not know the reimbursement rates until we are ready to market the product and we actually negotiate the rates.

There is significant uncertainty related to the insurance coverage and reimbursement of newly approved products. In the U.S., the Centers for Medicare & Medicaid Services, or CMS, an agency within the U.S. Department of Health and Human Services, decides whether and to what extent a new drug will be covered and reimbursed under Medicare. Private payors tend to follow the coverage reimbursement policies established by CMS to a substantial degree. It is difficult to predict what CMS or private payors will decide with respect to reimbursement for products such as ours, especially our gene therapy product candidates as there is a limited body of established practices and precedents for gene therapy products.

Outside the U.S., international operations are generally subject to extensive governmental price controls and other market regulations, and we believe the increasing emphasis on cost-containment initiatives in Europe, Canada, and other countries will put pressure on the pricing and usage of our products and product candidates. In many countries, the prices of medical products are subject to varying price control mechanisms as part of national health systems. Other countries allow companies to fix their own prices for medicinal products, but monitor and control company profits. Additional foreign price controls or other changes in pricing regulation could restrict the amount that we are able to charge for our product candidates. Accordingly, in markets outside the U.S., the reimbursement for our products may be reduced compared with the U.S. and may be insufficient to generate commercially reasonable revenue and profits. The timing to complete the negotiation process in each country is highly uncertain, and in some countries outside of the United States, we expect the process to exceed several months. Even if a price can be negotiated, countries frequently request or require reductions to the price and other concessions over time, including retrospective “clawback” price reductions. Additionally, member states of the EU have regularly imposed new or additional cost containment measures for pharmaceuticals such as volume discounts, cost caps, clawbacks and free products for a portion of the expected therapy period. For example, in France, we estimate clawback reserves on Dojolvi based on current regulations, our estimate of pricing on approval of Dojolvi and other factors. However, if pricing is approved at levels lower than estimated, if at all, or if there are further changes in the regulatory framework, we may be required to pay back amounts higher than clawback reserves and reverse revenue that has been previously recorded.

Moreover, increasing efforts by governmental and third-party payors in the U.S. and abroad to cap or reduce healthcare costs may cause such organizations to limit both coverage and the level of reimbursement for new products and, as a result, they may not cover or provide adequate payment for our products and product candidates. We expect to experience pricing pressures in connection with the sale of any of our products and product candidates due to the trend toward managed healthcare, the increasing influence of health maintenance organizations, additional legislative changes, including the impact from the Inflation Reduction Act of 2022, and statements by elected officials. For example, proposals have been discussed to tie U.S. drug prices to the cost in other countries, several states in the U.S. have introduced legislation to require pharmaceutical companies to disclose their costs to justify the prices of their products. Drug pricing is also expected to remain a focus for the current Presidential Administration and Congress. The downward pressure on healthcare costs in general, and with respect to prescription drugs, surgical procedures, and other treatments in particular, has become very intense. As a result, increasingly high barriers are being erected to the entry of new products.

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Risks Related to Our Intellectual Property

If we are unable to obtain and maintain effective patent rights for our products, product candidates, or any future product candidates, we may not be able to compete effectively in our markets.

We rely upon a combination of patents, trade secret protection, and confidentiality agreements to protect the intellectual property related to our technologies, our products, and our product candidates. Our success depends in large part on our and our licensors’ ability to obtain and maintain patent and other intellectual property protection in the U.S. and in other countries with respect to our proprietary technologies, our products, and our product candidates.

We have sought to protect our proprietary position by filing patent applications in the U.S. and abroad related to our novel technologies, products and product candidates that are important to our business. This process is expensive and time consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection.

The patent position of biotechnology and pharmaceutical companies generally is highly uncertain and involves complex legal and factual questions for which legal principles remain unsettled. The patent applications that we own or in-license may fail to result in issued patents with claims that cover our products or product candidates in the U.S. or in foreign countries. There is no assurance that all potentially relevant prior art relating to our patents and patent applications has been found, which can prevent a patent from issuing from a pending patent application or provide the basis for third parties to challenge the validity of an issued patent. Third parties may challenge the validity, enforceability, or scope of any issued patents, which may result in such patents being narrowed, found unenforceable, or invalidated. Furthermore, even if the patents and patent applications we own or in-license are unchallenged, they may not adequately protect our intellectual property, provide exclusivity for our products or product candidates, or prevent others from designing around our claims. Any of these outcomes could impair our ability to prevent competition from third parties.

We, independently or together with our licensors, have filed several patent applications covering various aspects of our products or product candidates. We cannot offer any assurances about which, if any, patents will issue, the breadth of any such patent, or whether any issued patents will be found invalid and unenforceable or will be threatened by third parties. Any successful opposition to these patents could impair the exclusivity position of our products or deprive us of rights necessary for the successful commercialization of any product candidates that are approved. Further, if we encounter delays in regulatory approvals, the period of time during which we could market a product candidate under patent protection could be reduced.

Our current patents or applications covering methods of use and certain compositions of matter do not provide complete patent protection for our products and product candidates in all territories. For example, there are no issued patents covering the Crysvita composition of matter in Latin America, where we have rights to commercialize this product. Therefore, a competitor could develop the same antibody or a similar antibody as well as other approaches that target FGF23 for potential commercialization in Latin America, subject to any intellectual property rights or regulatory exclusivities awarded to us. If we cannot obtain and maintain effective patent rights for our products or product candidates, we may not be able to compete effectively and our business and results of operations would be harmed.

We may not have sufficient patent terms to effectively protect our products and business.

Patents have a limited lifespan. In the U.S., the natural expiration of a patent is generally 20 years from its earliest non-provisional filing date. Although various extensions may be available, the life of a patent, and the protection it affords, is limited. Even if patents covering our products or product candidates are obtained, once the patent life has expired for a product, we may be open to competition from generic or biosimilar medications.

Patent term extensions under the Hatch-Waxman Act in the U.S. and under supplementary protection certificates in Europe may not be available to extend the patent exclusivity term for our products and product candidates, and we cannot provide any assurances that any such patent term extension will be obtained and, if so, for how long. Furthermore, we may not receive an extension if we fail to apply within applicable deadlines, fail to apply prior to expiration of relevant patents, or otherwise fail to satisfy applicable requirements. Moreover, the length of the extension could be less than we request. If we do not have sufficient patent terms or regulatory exclusivity to protect our products, our business and results of operations may be adversely affected.

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Patent law and rule changes could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents.

Changes in either the patent laws or interpretation of the patent laws in the U.S. and other countries may diminish the value of our patents or narrow the scope of our patent protection. The laws of foreign countries may not protect our rights to the same extent as the laws of the U.S. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the U.S. and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all. We therefore cannot be certain that we or our licensors were the first to make the invention claimed in our owned and in-licensed patents or pending applications, or that we or our licensor were the first to file for patent protection of such inventions.

In 2011, the Leahy-Smith America Invents Act, or the Leahy-Smith Act, was signed into law and introduced significant changes to the prosecution of U.S. patent applications and to the procedures for challenging U.S. patents. The effects of these changes still remain unclear owing to the evolving nature of the law and the lengthy timelines associated with court system review and interpretation. However, the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business and financial condition.

Outside the U.S., there have been changes to patent laws in certain jurisdictions that could impair our ability to obtain, maintain, or enforce our patents in those territories. For instance, Europe’s new Unitary Patent system and Unified Patent Court (the “UPC”) may present uncertainties for our ability to protect and enforce our patent rights against competitors in Europe. In 2012, as part of the European Patent Package (the “EU Patent Package”), regulations were passed with the goal of providing a single pan-European Unitary Patent system and a new UPC, for litigation involving European patents. Implementation of the EU Patent Package occurred in June 2023. Under the UPC, all European patents, including those issued prior to ratification of the European Patent Package, will by default automatically fall under the jurisdiction of the UPC. The UPC will provide our competitors with a new forum in which to seek central revocation of our European patents and allow for the possibility of a competitor to obtain pan-European injunctions. It will be several years before we will understand the scope of patent rights that will be recognized and the strength of patent remedies that will be provided by the UPC. Under the EU Patent Package, we will have the right to opt our patents out of the UPC over the first seven years of the court’s existence, but doing so may preclude us from realizing the benefits of the new unified court.

If we are unable to maintain effective proprietary rights for our products, product candidates, or any future product candidates, we may not be able to compete effectively in our markets.

In addition to the protection afforded by patents, we rely on trade secret protection and confidentiality agreements to protect proprietary know-how that is not patentable or that we elect not to patent, processes for which patents are difficult to enforce and any other elements of our products or product candidate discovery and development processes that involve proprietary know-how, information, or technology that is not covered by patents. However, trade secrets can be difficult to protect. The confidentiality agreements entered into with our employees, consultants, scientific advisors, contractors and other third parties that we rely on in connection with the development, manufacture and commercialization of our products may not be sufficient to protect our proprietary technology and processes, which increase the risk that such trade secrets may become known by our competitors or may be inadvertently incorporated into the technology of others.

The physical security of our premises and physical and electronic security of our information technology systems may not preserve the integrity and confidentiality of our data and trade secrets. These individuals, organizations and systems, agreements or security measures may be breached, and we may not have adequate remedies for any breach. In addition, our trade secrets may otherwise become known or be independently discovered by competitors.

The assignment agreements we enter into with our employees and consultants to assign their inventions to us, and the confidentiality agreements we enter into with our employees, consultants, advisors, and any third parties who have access to our proprietary know-how, information, or technology may not have been duly executed and we cannot assure that our trade secrets and other confidential proprietary information will not be disclosed or that competitors will not otherwise gain access to our trade secrets or independently develop substantially equivalent information and techniques. Misappropriation or unauthorized disclosure of our trade secrets could impair our competitive position and may have a material adverse effect on our business. Additionally, if the steps taken to maintain our trade secrets are deemed inadequate, we may have insufficient recourse against third parties for misappropriating the trade secret.

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Claims of intellectual property infringement may prevent or delay our development and commercialization efforts.

Our commercial success depends in part on our avoiding infringement of the patents and proprietary rights of others. There have been many lawsuits and other proceedings involving patent and other intellectual property rights in the biotechnology and pharmaceutical industries, including patent infringement lawsuits, interferences, inter partes reviews, post grant reviews, oppositions, and reexamination proceedings before the USPTO and corresponding foreign patent offices. Numerous U.S. and foreign issued patents and pending patent applications, which are owned by other parties, exist in the fields in which we are developing product candidates. As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our products or product candidates may be subject to claims of infringement of the patent rights of these other parties.

Other parties may assert that we are employing their proprietary technology without authorization. There may be patents or patent applications with claims to materials, formulations, methods of manufacture, or methods for treatment relevant to the use or manufacture of our products or product candidates. We have conducted freedom to operate analyses with respect only to our products and certain of our product candidates, and therefore we do not know whether there are any patents of other parties that would impair our ability to commercialize all of our product candidates. We also cannot guarantee that any of our analyses are complete and thorough, nor can we be sure that we have identified each and every patent and pending application in the U.S. and abroad that is relevant or necessary to the commercialization of our products or product candidates. Because patent applications can take many years to issue, there may be currently pending patent applications that may later result in issued patents that are relevant to our products or product candidates.

We are aware of certain U.S. and foreign patents owned by third parties that a court might construe to be valid and relevant to one or more of our gene therapy product candidates, certain methods that may be used in their manufacture or delivery, or certain formulations comprising one or more of our gene therapy candidates. Regarding our anti-sclerostin antibody product candidate, setrusumab, we are aware of litigation involving patents owned by a third-party, OssiFi-Mab LLC (OMab), relating to methods of using sclerostin antagonists in combination with antiresorptive drugs to increase bone growth, bone formation, and/or bone density. Specifically, in the U.S., OMab has asserted certain patents expiring in 2027 or 2028 against Amgen based on Amgen’s commercialization of an anti-sclerostin antibody, Evenity®, for the treatment of osteoporosis in postmenopausal women at high risk for fracture; Amgen denies infringement and asserts the OMab patents are invalid. In Europe, OMab was granted two patents with related subject matter; the first patent has been revoked while the second has been opposed by Amgen, UCB, and two anonymous parties. There is a risk that one or more third parties may choose to engage in litigation with us to enforce or to otherwise assert their patent rights against us. Even if we believe such claims are without merit, a court of competent jurisdiction could hold that one or more of these patents is valid, enforceable, and infringed, in which case the owners of any such patents may be able to block our ability to commercialize a product candidate unless we obtain a license under the applicable patents, or until such patents expire. However, such a license may not be available on commercially reasonable terms or at all.

Parties making claims against us may obtain injunctive or other equitable relief, which could effectively block our ability to continue commercialization of our products, or block our ability to develop and commercialize one or more of our product candidates. Defense of these claims, regardless of their merit, would involve substantial litigation expense and would be a substantial diversion of employee resources from our business. In the event of a successful claim of infringement against us, we may have to pay substantial damages, including treble damages and attorneys’ fees for willful infringement, pay royalties, redesign our infringing products, or obtain one or more licenses from third parties, which may be impossible or require substantial time and monetary expenditure.

We may not be successful in obtaining or maintaining necessary rights to our product candidates through acquisitions and in-licenses.

Because our programs may require the use of proprietary rights held by third parties, the growth of our business will likely depend in part on our ability to acquire, in-license, or use these proprietary rights. We may be unable to acquire or in-license any compositions, methods of use, processes, or other third-party intellectual property rights from third parties that we identify as necessary for our product candidates. The licensing and acquisition of third-party intellectual property rights is a competitive area, and a number of more established companies are also pursuing strategies to license or acquire third-party intellectual property rights that we may consider attractive. These established companies may have a competitive advantage over us due to their size, cash resources, and greater clinical development and commercialization capabilities. In addition, companies that perceive us to be a competitor may be unwilling to assign or license rights to us. We also may be unable to license or acquire third-party intellectual property rights on terms that would allow us to make an appropriate return on our investment.

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We sometimes collaborate with U.S. and foreign academic institutions to accelerate our preclinical research or development under written agreements with these institutions. Typically, these institutions provide us an option to negotiate a license to any of the institution’s rights in technology resulting from the collaboration. Regardless of such option, we may be unable to negotiate a license within the specified timeframe or under terms that are acceptable to us. If we are unable to do so, the institution may offer the intellectual property rights to other parties, potentially blocking our ability to pursue our program.

If we are unable to successfully obtain rights to required third-party intellectual property rights or maintain the existing intellectual property rights we have, we may have to abandon development of the corresponding program.

We may face competition from biosimilars, which may have a material adverse impact on the future commercial prospects of our biological products and product candidates.

Even if we are successful in achieving regulatory approval to commercialize a product candidate faster than our competitors, we may face competition from biosimilars with respect to our biological products (Crysvita, Mepsevii and Evkeeza) and our biological product candidates. In the U.S., the Biologics Price Competition and Innovation Act of 2009, or BPCI Act, was included in the Affordable Care Act and created an abbreviated approval pathway for biological products that are demonstrated to be “highly similar,” or biosimilar, to or “interchangeable” with an FDA-approved biological product. The BPCI Act prohibits the FDA from approving a biosimilar or interchangeable product that references a brand biological product until 12 years after the licensure of the reference product, but permits submission of an application for a biosimilar or interchangeable product to the FDA four years after the reference product was first licensed. The BPCI Act does not prevent another company from developing a product that is highly similar to the innovative product, generating its own data, and seeking approval. The law is complex and is still being interpreted and implemented by the FDA. Moreover, aspects of the law are still being evaluated and interpreted by courts. As a result, its ultimate impact, implementation and meaning are subject to uncertainty. Modification of the BPCI Act, or changes to the interpretation or implementation of the BPCI Act, could have a material adverse effect on the future commercial prospects for our biological products and product candidates.

In Europe, the European Commission has granted marketing authorizations for several biosimilars pursuant to a set of general and product class-specific guidelines for biosimilar approvals issued over the past few years. In Europe, a competitor may reference data supporting approval of an innovative biological product, but will not be able to get on the market until 10 years after the time of approval of the innovative product. This 10-year marketing exclusivity period will be extended to 11 years if, during the first eight of those 10 years, the marketing authorization holder obtains an approval for one or more new therapeutic indications that bring significant clinical benefits compared with existing therapies. In addition, companies may be developing biosimilars in other countries that could compete with our products.

If competitors are able to obtain marketing approval for biosimilars referencing our products, our products may become subject to competition from such biosimilars, with the attendant competitive pressure and consequences.

Competitors could enter the market with generic versions of Dojolvi or our small-molecule product candidates, which may result in a material decline in sales of affected products.

Under the Hatch-Waxman Act, a pharmaceutical manufacturer may file an abbreviated new drug application, or ANDA, seeking approval of a generic copy of an approved innovator product. Under the Hatch-Waxman Act, a manufacturer may also submit an NDA under section 505(b)(2) that references the FDA’s finding of safety and effectiveness of a previously approved drug. A 505(b)(2) NDA product may be for a new or improved version of the original innovator product. Innovative small molecule drugs may be eligible for certain periods of regulatory exclusivity (e.g., five years for new chemical entities, three years for changes to an approved drug requiring a new clinical study, and seven years for orphan drugs), which preclude FDA approval (or in some circumstances, FDA filing and review of) an ANDA or 505(b)(2) NDA relying on the FDA’s finding of safety and effectiveness for the innovative drug. In addition to the benefits of regulatory exclusivity, an innovator NDA holder may have patents claiming the active ingredient, product formulation or an approved use of the drug, which would be listed with the product in the “Orange Book.” If there are patents listed in the Orange Book, a generic applicant that seeks to market its product before expiration of the patents must include in the ANDA or 505(b)(2) what is known as a “Paragraph IV certification,” challenging the validity or enforceability of, or claiming non-infringement of, the listed patent or patents. Notice of the certification must be given to the innovator, too, and if within 45 days of receiving notice the innovator sues to enforce its patents, approval of the ANDA is stayed for 30 months, or as lengthened or shortened by the court.

Accordingly, competitors could file ANDAs for generic versions of our small-molecule product, Dojolvi, or 505(b)(2) NDAs that reference Dojolvi. For the patents listed for Dojolvi in the Orange Book, those ANDAs and 505(b)(2) NDAs would be required to include a certification as to each listed patent indicating whether the ANDA applicant does or does not intend to challenge the patent. We cannot predict how any generic competitor would address such patents, whether we would sue on any such patents, or the outcome of any such suit.

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There have been a number of recent regulatory and legislative initiatives designed to encourage generic competition for small-molecule pharmaceutical products. For instance, in December 2019, the Creating and Restoring Equal Access to Equivalent Samples Act, or the CREATES Act, was enacted, which provides a legislatively defined private right of action under which eligible product developers can bring suit against companies who refuse to sell sufficient quantities of their branded products on commercially reasonable, market-based terms to support such eligible product developers’ marketing applications. It is our policy to evaluate requests for samples of our branded products, and to provide samples in response to bona fide, CREATES Act-compliant requests from qualified third parties, including generic manufacturers. We have received requests for samples of Dojolvi, and when appropriate, we have sold samples of Dojolvi to eligible product developers in compliance with the requirements of the CREATES Act.

We may not be successful in securing or maintaining proprietary patent protection for products and technologies we develop or license. Moreover, if any patents that are granted and listed in the Orange Book are successfully challenged by way of a Paragraph IV certification and subsequent litigation, the affected product could more immediately face generic competition and its sales would likely decline materially. For instance, if competitors develop generic version of Dojolvi and are able to enter the market, our sales of Dojolvi could materially decline which could have an adverse impact on our financial results.

The patent protection and patent prosecution for some of our products and product candidates is dependent on third parties.

While we normally seek and gain the right to fully prosecute the patents relating to our products or product candidates, there may be times when patents relating to our products or product candidates are controlled by our licensors. This is the case with our license agreements with KKC and Regeneron, who are primarily responsible for the prosecution of certain patents and patent applications covering Crysvita and Evkeeza, respectively.

In addition, we have in-licensed various patents and patent applications owned by the University of Pennsylvania relating to our DTX301, DTX401 and/or UX701 product candidates. Some of these patents and patent applications are licensed or sublicensed by REGENX and sublicensed to us. We do not have the right to control the prosecution of these patent applications, or the maintenance of any of these patents. In addition, under our agreement with REGENX, we do not have the first right to enforce the licensed patents, and our enforcement rights are subject to certain limitations that may adversely impact our ability to use the licensed patents to exclude others from commercializing competitive products. Moreover, REGENX and the University of Pennsylvania may have interests which differ from ours in determining whether to enforce and the manner in which to enforce such patents.

If KKC, Regeneron, the University of Pennsylvania, REGENX, or any of our future licensing partners fail to appropriately prosecute, maintain, and enforce patent protection for the patents covering any of our products or product candidates, our ability to develop and commercialize those products or product candidates may be adversely affected and we may not be able to prevent competitors from making, using, and selling competing products. In addition, even where we now have the right to control patent prosecution of patents and patent applications we have licensed from third parties, we may still be adversely affected or prejudiced by actions or inactions of our licensors and their counsel that took place prior to us assuming control over patent prosecution.

If we fail to comply with our obligations in the agreements under which we license intellectual property and other rights from third parties or otherwise experience disruptions to our business relationships with our licensors, we could lose license rights that are important to our business.

We are a party to a number of intellectual property license agreements that are important to our business and expect to enter into additional license agreements in the future. Our existing license agreements impose, and we expect that future license agreements will impose, various diligence, milestone payment, royalty, and other obligations on us. If we fail to comply with our obligations under these agreements, or we are subject to a bankruptcy, we may be required to make certain payments to the licensor, we may lose the exclusivity of our license, or the licensor may have the right to terminate the license, in which event we would not be able to develop or market products covered by the license. Additionally, the milestone and other payments associated with these licenses will make it less profitable for us to develop our product candidates.

In certain cases, we control the prosecution of patents resulting from licensed technology. In the event we breach any of our obligations related to such prosecution, we may incur significant liability to our licensing partners. Licensing of intellectual property is of critical importance to our business and involves complex legal, business, and scientific issues. Disputes may arise regarding intellectual property subject to a licensing agreement, including but not limited to:

•the scope of rights granted under the license agreement and other interpretation-related issues;

•the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement;

•the sublicensing of patent and other rights;

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•our diligence obligations under the license agreement and what activities satisfy those diligence obligations;

•the ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our collaborators; and

•the priority of invention of patented technology.

If disputes over intellectual property and other rights that we have licensed prevent or impair our ability to maintain our current licensing arrangements on acceptable terms, we may be unable to successfully develop and commercialize the affected product candidates.

We may become involved in lawsuits to protect or enforce our patents or the patents of our licensors, or be subject to claims that challenge the inventorship or ownership of our patents or other intellectual property, which could be expensive, time consuming, and result in unfavorable outcomes.

Competitors may infringe our patents or the patents of our licensors. If we or one of our licensing partners were to initiate legal proceedings against a third party to enforce a patent covering our products or one of our product candidates, the defendant could counterclaim that the patent covering our product or product candidate is invalid and/or unenforceable. In patent litigation in the U.S., defendant counterclaims alleging invalidity and/or unenforceability are commonplace. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, or non-enablement. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant information from the USPTO, or made a misleading statement, during prosecution. The outcome following legal assertions of invalidity and unenforceability is unpredictable.

Interference proceedings or derivation proceedings now available under the Leahy-Smith Act provoked by third parties or brought by us or declared or instituted by the USPTO may be necessary to determine the priority of inventions with respect to our patents or patent applications or those of our licensors. An unfavorable outcome could require us to cease using the related technology or to attempt to license rights to it from the prevailing party. Our business could be harmed if the prevailing party does not offer us a license on commercially reasonable terms. In addition, the validity of our patents could be challenged in the USPTO by one of the new post grant proceedings (i.e., inter partes review or post grant review) now available under the Leahy-Smith Act. Our defense of litigation, interference proceedings, or post grant proceedings under the Leahy-Smith Act may fail and, even if successful, may result in substantial costs and distract our management and other employees.

We may in the future also be subject to claims that former employees, collaborators, or other third parties have an interest in our patents as an inventor or co-inventor. In addition, we may have ownership disputes arise from conflicting obligations of consultants or others who are involved in developing our product candidates. Litigation may be necessary to defend against these and other claims challenging inventorship or ownership. If we fail to successfully defend against such litigation or claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, valuable intellectual property.

Even if we are successful in defending against such litigation and claims, such proceedings could result in substantial costs and distract our management and other employees. Because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during litigation. There could also be public announcements of the results of hearings, motions, or other interim proceedings or developments related to such litigation or claims. If securities analysts or investors perceive these results to be negative, it could have a material adverse effect on the price of our common stock.

We may be subject to claims that our employees, consultants, or independent contractors have wrongfully used or disclosed confidential information of third parties or that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.

We employ certain individuals who were previously employed at universities or other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Our efforts to vet our employees, consultants, and independent contractors and prevent their use of the proprietary information or know-how of others in their work for us may not be successful, and we may in the future be subject to claims that our employees, consultants, or independent contractors have wrongfully used or disclosed confidential information of third parties. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel, which could adversely impact our business. Even if we are successful in defending against such claims, litigation could result in substantial costs and distract management and other employees.

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Changes to patent laws in the U.S. and other jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our products.

As is the case with other biotechnology and pharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining and enforcing patents in the biotechnology and pharmaceutical industries involves both technological and legal complexity. Therefore, obtaining and enforcing such patents is costly, time consuming, and inherently uncertain.

In recent years, the U.S. Supreme Court has ruled on several patent cases, and in some instances, narrowed the scope of patent protection available. In addition, there have been recent proposals for changes to U.S. laws that, if adopted, could impact our ability to obtain or maintain patent protection for our proprietary technologies. Depending on future actions by U.S. courts, U.S. Congress, the USPTO, and the relevant law making bodies in other countries, the laws and regulations governing patents could change in unpredictable ways that could weaken our ability to obtain new patents, shorten the term of our existing patents and patents that we might obtain in the future, or impair the validity or enforceability of our patents that may be asserted against our competitors or other third parties. Any of these outcomes could have a material adverse effect on our business. For example, with respect to patent term adjustment (PTA), the Federal Circuit’s recent holding in In re Cellect, LLC, 81 F.4th 1216 (Fed. Cir. 2023), that the obviousness-type double patenting analysis for a patent that has received PTA must be based on the expiration date of the patent after the PTA has been added, may negatively impact the validity and/or term of certain of our owned or in-licensed U.S. patents.

We may not be able to protect our intellectual property rights throughout the world.

Filing, prosecuting, and defending patents on our products or product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the U.S. can be less extensive than those in the U.S. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the U.S. Further, licensing partners such as KKC and Regeneron may not prosecute patents in certain jurisdictions in which we may obtain commercial rights, thereby precluding the possibility of later obtaining patent protection in these countries. Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the U.S., or from selling or importing products made using our inventions in and into the U.S. or other jurisdictions. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and may also export infringing products to territories where we have patent protection, but enforcement is not as strong as that in the U.S. These products may compete with our products, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.

Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents, trade secrets, and other intellectual property protection, particularly those relating to biotechnology products, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally. Proceedings to enforce our patent rights in foreign jurisdictions, whether or not successful, could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly, could put our patent applications at risk of not issuing, and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

Risks Related to Our Business Operations

We have limited experience as a company operating our own manufacturing facility and may experience unexpected costs or challenges.

We completed construction of our gene therapy manufacturing facility in Bedford, Massachusetts in 2023. Prior to construction of this facility, we did not previously have experience as a company in operating our own manufacturing facility and at this point, we cannot assure that the facility will be fully utilized at all times, particularly as we have only recently commenced our manufacturing operations. Our limited experience may contribute to unacceptable or inconsistent product quality success rates and yields, and we may be unable to maintain adequate quality control, quality assurance, and qualified personnel. We have incurred and will continue to incur significant expenses and costs to operate the facility, which may be subject to significant impairment if our gene therapy programs are unsuccessful. Before we can begin to commercially manufacture any of our product candidates at the facility, we must obtain regulatory approval from the FDA for our manufacturing processes and for the facility. In order to obtain approval, we will need to ensure that all of our processes, quality systems, methods, equipment, policies and procedures are

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compliant with cGMP. Until recently, few gene therapy products manufactured by a cGMP gene therapy manufacturing facility in the U.S. had received approval from the FDA; therefore, the time frame required for us to obtain such approval is uncertain. The cGMP requirements govern quality control of the manufacturing process and documentation policies and procedures. In complying with cGMP, we will be obligated to spend time, money and effort on production, record keeping and quality control to assure that the product meets applicable specifications and other requirements. If we fail to comply with these requirements, we would be subject to possible regulatory action and may not be permitted to sell any products that we may develop.

As we seek to optimize and operate our manufacturing process at the facility, we will likely face technical and scientific challenges, considerable capital costs and potential difficulty in recruiting and hiring experienced, qualified personnel at the facility which could result in delays in our production or difficulties in maintaining compliance with applicable regulatory requirements. We may also experience unexpected technical, regulatory, safety, quality or operational issues during manufacturing campaigns. As we expand our commercial footprint to multiple geographies, we may establish multiple manufacturing facilities, which may lead to regulatory delays or prove costly. Even if we are successful, we cannot assure that such additional capacity will be required or that our investment will be recouped. Further, our manufacturing capabilities could be affected by cost-overruns, unexpected delays, equipment failures, lack of capacity, labor shortages, natural disasters, power failures, program failures, actual or threatened public health emergencies, and numerous other factors that could prevent us from realizing the intended benefits of our manufacturing strategy.

Our future success depends in part on our ability to retain our Founder, President, and Chief Executive Officer and to attract, retain, and motivate other qualified personnel.

We are dependent on Emil D. Kakkis, M.D., Ph.D., our Founder, President, and Chief Executive Officer, the loss of whose services may adversely impact the achievement of our objectives. Dr. Kakkis could leave our employment at any time, as he is an “at will” employee. Recruiting and retaining other qualified employees, consultants, and advisors for our business, including scientific and technical personnel, will also be critical to our success. There is currently a shortage of skilled personnel in our industry, which is likely to continue. As a result, competition for skilled personnel is intense and the turnover rate can be high. In addition, failure to succeed in preclinical or clinical studies may make it more challenging to recruit and retain qualified personnel. Over the last several years, we have also experienced certain executive leadership changes. Leadership transitions are inherently difficult to manage, cause uncertainty and disruption and could increase the likelihood of turnover of other key officers and employees. The inability to recruit and retain qualified personnel, or the loss of the services of Dr. Kakkis or any of other member of our executive leadership team or other key employee, may impede the progress of our research, development, and commercialization objectives.

If we fail to obtain or maintain orphan drug exclusivity for our products, our competitors may sell products to treat the same conditions and our revenue will be reduced.

Our business strategy focuses on the development of drugs that are eligible for FDA and EU orphan drug designation. In the U.S., orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical study costs, tax advantages, and user-fee waivers. In addition, if a product receives the first FDA approval for the indication for which it has orphan designation, the product is entitled to orphan drug exclusivity, which means the FDA may not approve any other application to market the same drug for the same indication for a period of seven years, except in limited circumstances, such as a showing of clinical superiority over the product with orphan exclusivity or where the manufacturer is unable to assure sufficient product quantity. In the EU, orphan drug designation entitles a party to financial incentives such as reduction of fees or fee waivers and ten years of market exclusivity following drug or biological product approval. This period may be reduced to six years if the orphan drug designation criteria are no longer met, including where it is shown that the product is sufficiently profitable not to justify maintenance of market exclusivity.

Because the extent and scope of patent protection for our products may in some cases be limited, orphan drug designation is especially important for our products for which orphan drug designation may be available. For eligible drugs, we plan to rely on the exclusivity period under the Orphan Drug Act to maintain a competitive position. If we do not obtain orphan drug exclusivity for our drug products and biologic products that do not have broad patent protection, our competitors may then sell the same drug to treat the same condition sooner than if we had obtained orphan drug exclusivity, and our revenue will be reduced.

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Even though we have orphan drug designation for UX111, UX143, DTX301, DTX401 and UX701 in the U.S. and Europe and for GTX 102 in the U.S., we may not be the first to obtain marketing approval for any particular orphan indication due to the uncertainties associated with developing pharmaceutical products. Further, even if we obtain orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from competition because different drugs with different active moieties can be approved for the same condition or the same drug can be approved for a different indication unless there are other exclusivities such as new chemical entity exclusivity preventing such approval. Even after an orphan drug is approved, the FDA or EMA can subsequently approve the same drug with the same active moiety for the same condition if the FDA or EMA concludes that the later drug is safer, more effective, or makes a major contribution to patient care. Orphan drug designation neither shortens the development time or regulatory review time of a drug nor gives the drug any advantage in the regulatory review or approval process.

Our operating results would be adversely impacted if our intangible assets become impaired.

We have recorded on our Consolidated Balance Sheets intangible assets for in-process research and development, or IPR&D, related to DTX301 and DTX401 as a result of the accounting for our acquisition of Dimension Therapeutics. We also recorded an intangible asset related to our license from Regeneron for Evkeeza. We test the intangible assets for impairment annually during the fourth quarter and more frequently if events or changes in circumstances indicate that it is more likely than not that the asset is impaired. If the associated research and development effort is abandoned, the related assets will be written-off and we will record a noncash impairment loss on our Consolidated Statement of Operations. We have not recorded any impairments related to our intangible assets through December 31, 2023.

We may not be successful in our efforts to identify, license, discover, develop, or commercialize additional product candidates.

The success of our business depends upon our ability to identify, license, discover, develop, or commercialize additional product candidates in addition to the continued clinical testing, potential approval, and commercialization of our existing product candidates. Research programs to identify and develop new product candidates require substantial technical, financial, and human resources. We may focus our efforts and resources on potential programs or product candidates that ultimately prove to be unsuccessful. Our research programs or licensing efforts may fail to yield additional product candidates for clinical development and commercialization for a number of reasons, including but not limited to the following:

•our research or business development methodology or search criteria and process may be unsuccessful in identifying potential product candidates;

•we may not be able or willing to assemble sufficient technical, financial or human resources to acquire or discover additional product candidates;

•we may face competition in obtaining and/or developing additional product candidates;

•our product candidates may not succeed in research, discovery, preclinical or clinical testing;

•our potential product candidates may be shown to have harmful side effects or may have other characteristics that may make the products unmarketable or unlikely to receive marketing approval;

•competitors may develop alternatives that render our product candidates obsolete or less attractive;

•product candidates we develop may be covered by third parties’ patents or other exclusive rights;

•the market for a product candidate may change during our program so that such a product may become unreasonable to continue to develop;

•a product candidate may not be capable of being produced in commercial quantities at an acceptable cost or at all; and

•a product candidate may not be accepted as safe and effective by regulatory authorities, patients, the medical community, or payors.

If any of these events occur, we may be forced to abandon our development efforts for a program or programs, or we may not be able to identify, license, discover, develop, or commercialize additional product candidates, which would have a material adverse effect on our business and could potentially cause us to cease operations.

We may expend our limited resources to pursue a particular product, product candidate or indication and fail to capitalize on products, product candidates or indications that may be more profitable or for which there is a greater likelihood of success.

Because we have limited financial and managerial resources, we focus our sales, marketing and research programs on certain products, product candidates or for specific indications. As a result, we may forego or delay pursuit of opportunities with other

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products or product candidates or other indications that later prove to have greater commercial potential. Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities. Our spending on current and future research and development programs and product candidates may not yield any commercially viable products. If we do not accurately evaluate the commercial potential or target market for a particular product or product candidate, we may relinquish valuable rights through collaboration, licensing, or other royalty arrangements in cases in which it would have been advantageous for us to retain sole development and commercialization rights or we may allocate internal resources to a product candidate in a therapeutic area in which it would have been more advantageous to enter into a partnering arrangement.

Changes to healthcare and FDA laws, regulations, and policies may have a material adverse effect on our business and results of operations.

As described above in “Item 1. Business - Government Regulation” and in the Risk Factor above entitled “ – The insurance coverage and reimbursement status of newly approved products is uncertain” there have been and continue to be a number of legislative initiatives to contain healthcare costs and to modify the regulation of drug and biologic products. We expect that additional state and federal healthcare reform measures and regulations will be adopted in the future, including proposals to reduce the exclusivity protections provided to already approved biological products and to provide biosimilar and interchangeable biologic products an easier path to approval. Any of these measures and regulations could limit the amounts that federal and state governments will pay for healthcare products and services, result in reduced demand for our product candidates or additional pricing pressures and affect our product development, testing, marketing approvals and post-market activities.

Failure to comply with laws and regulations could harm our business and our reputation.

Our business is subject to regulation by various federal, state, local and foreign governmental agencies, including agencies responsible for monitoring and enforcing employment and labor laws, workplace safety, privacy and security laws and regulations, and tax laws and regulations. In certain jurisdictions, these regulatory requirements may be more stringent than those in the U.S., and in other circumstances these requirements may be more stringent in the U.S.

In particular, our operations are directly, and indirectly through our customers, subject to various federal and state fraud and abuse laws, including, without limitation, the federal Anti-Kickback Statute, the federal False Claims Act, and physician sunshine laws and regulations; and patient and non-patient privacy regulations, including the GDPR and the California Consumer Privacy Act, or CCPA, including amendments from the California Privacy Rights Act, or CPRA, as described above in “Item 1. Business – Government Regulation”. Because of the breadth of these laws and the narrowness of the statutory exceptions and safe harbors available, it is possible that some of our business activities could be subject to challenge under one or more of such laws. For instance, one of our programs for sponsored genetic testing to help patients receive an accurate diagnosis was previously the subject of review by applicable governmental authorities of compliance with various fraud and abuse laws. We settled the matter with the governmental authorities for an immaterial settlement amount and without any admission of legal liability. We cannot assure that our other operations or programs will not be subject to review by governmental authorities or found to violate such laws.

The GDPR imposes a number of strict obligations and restrictions on the ability to process personal data of individuals, in particular with respect to special categories of personal data like health data (e.g., reliance on a legal basis, information to individuals, notification to relevant national data protection authorities in case of personal data breach and implementation of appropriate security measures). EU member states may also impose additional requirements in relation to special categories of personal data through their national legislation. In addition, the GDPR imposes specific restrictions on the transfer of personal data to countries outside of the EEA that are not considered by the European Commission as providing an adequate level of protection (including the U.S.). Appropriate safeguards are required to enable such transfers (e.g., reliance on standard contractual clauses and transfer risk assessments). There are also several compliance requirements under the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and implementing regulations that create requirements relating to the privacy and security of protected health information. Those requirements are also applicable, in many instances, to business associates of covered entities. In some cases, depending on our business operations and contractual agreements, including through the conduct of clinical trials, we are subject to HIPAA requirements. Also, we may be subject to additional federal, state and local privacy laws and regulations in the U.S., including new and recently enacted laws (such as CCPA and CPRA), that may apply to us and/or our service providers now or in the future and that require that we take measures to be transparent regarding, honor rights with respect to, and protect the privacy and security of certain information we gather and use in our business, including personal information, particularly personal information that is not otherwise subject to HIPAA.

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If our operations are found to be in violation of any of the laws described above or any other governmental regulations that apply to us, we may be subject to penalties, including civil and criminal penalties, damages, fines, exclusion from participation in government health care programs, such as Medicare and Medicaid, imprisonment, disgorgement of profits, and the curtailment or restructuring of our operations. If any governmental sanctions, fines, or penalties are imposed, or if we do not prevail in any possible civil or criminal litigation, our business, operating results, financial condition and our reputation could be harmed. In addition, responding to any action will likely result in a significant diversion of management’s attention and resources and an increase in professional fees.

Our research and development activities, including our process and analytical development activities in our quality control laboratory, and our and our third-party manufacturers’ and suppliers’ activities, including activities related to the build-out and operation of our gene therapy manufacturing facility, involve the controlled storage, use, and disposal of hazardous materials, including the components of our product candidates, such as viruses, and other hazardous compounds, which subjects us to laws and regulations governing such activities. In some cases, these hazardous materials and various wastes resulting from their use are stored at our or our manufacturers’ facilities pending their use and disposal. We cannot eliminate the risk of contamination, which could cause an interruption of our commercialization efforts, research and development efforts, and business operations or environmental damage that could result in costly clean-up and liabilities under applicable laws and regulations governing the use, storage, handling, and disposal of these materials and specified waste products. We cannot guarantee that the safety procedures utilized by us and our third-party manufacturers for handling and disposing of these materials comply with the standards prescribed by these laws and regulations, or eliminate the risk of accidental contamination or injury from these materials. In such an event, we may be held liable for any resulting damages—and such liability could exceed our resources—and state or federal or other applicable authorities may curtail our use of certain materials and/or interrupt our business operations. Furthermore, environmental laws and regulations are complex, change frequently, and have tended to become more stringent. We cannot predict the impact of such changes and cannot be certain of our future compliance.

Additionally, as we and our employees increasingly use social media tools as a means of communication with the public, there is a risk that the use of social media by us or our employees to communicate about our products or business may cause to be found in violation of applicable laws, despite our attempts to monitor such social media communications through company policies and guidelines. In addition, our employees may knowingly or inadvertently make use of social media in ways that may not comply with our company policies or other legal or contractual requirements, which may give rise to liability, lead to the loss of trade secrets or other intellectual property, cause reputational harm or result in public exposure of personal information of our employees, clinical trial patients, customers, and others.

International expansion of our business exposes us to business, regulatory, political, operational, financial, and economic risks associated with doing business outside of the U.S.

Our business strategy includes international expansion. We currently conduct clinical studies and regulatory activities and we also commercialize products outside of the U.S. Doing business internationally involves a number of risks, including but not limited to:

•multiple, conflicting, and changing laws and regulations such as privacy and data regulations, transparency regulations, tax laws, export and import restrictions, employment laws, regulatory requirements, and other governmental approvals, permits, and licenses;

•introduction of new health authority requirements and/or changes in health authority expectations;

•failure by us to obtain and maintain regulatory approvals for the use of our products in various countries;

•additional potentially relevant third-party patent rights;

•complexities and difficulties in obtaining protection for, and enforcing, our intellectual property;

•difficulties in staffing and managing foreign operations;

•complexities associated with managing multiple payor reimbursement regimes, government payors, or patient self-pay systems;

•limits on our ability to penetrate international markets;

•financial risks, such as longer payment cycles, additional or more burdensome regulatory requirements of financial institutions outside of the U.S., difficulty collecting accounts receivable, the impact of local and regional financial crises on demand and payment for our products, and exposure to foreign currency exchange rate fluctuations;

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•natural disasters and geopolitical and economic instability, including wars, terrorism, political unrest (including, for example the conflict between Russia and Ukraine, the conflict between Israel and the surrounding areas, and the rising tensions between China and Taiwan), results of certain elections and votes, actual or threatened public health emergencies and outbreak of disease, rising inflation, the potential recessionary environment, the potential shutdown of the U.S. federal government, boycotts and resulting staffing shortages, adoption or expansion of government trade restrictions, and other business restrictions;

•certain expenses including, among others, expenses for travel, translation, and insurance;

•regulatory and compliance risks that relate to maintaining accurate information and control over commercial operations and activities that may fall within the purview of the U.S. Foreign Corrupt Practices Act, or FCPA, its books and records provisions, or its anti-bribery provisions, including those under the U.K. Bribery Act and similar foreign laws and regulations; and

•regulatory and compliance risks relating to doing business with any entity that is subject to sanctions administered by the Office of Foreign Assets Control of the U.S. Department of the Treasury.

Any of these factors could significantly harm our future international expansion and operations and, consequently, our results of operations.

Our business and operations may be materially adversely affected in the event of computer system failures or security breaches.

Cybersecurity incidents, including phishing attacks and attempts to misappropriate or compromise confidential or proprietary information or sabotage enterprise IT systems are becoming increasingly frequent and more sophisticated. The information and data processed and stored in our technology systems, and those of our strategic partners, CROs, contract manufacturers, suppliers, distributors or other third parties for which we depend to operate our business, may be vulnerable to loss, damage, denial-of-service, unauthorized access or misappropriation. Data security breaches can occur as a result of malware, hacking, business email compromise, ransomware attacks, phishing or other cyberattacks directed by third parties. We, and certain of the third parties for which we depend on to operate our business, have experienced cybersecurity incidents, including third party unauthorized access to and misappropriation of financial information, and may experience similar incidents in the future. Further, risks of unauthorized access and cyber-attacks have increased as most of our personnel, and the personnel of many third-parties with which we do business, have adopted hybrid working arrangements following the COVID-19 pandemic. Improper or inadvertent behavior by employees, contractors and others with permitted access to our systems, pose a risk that sensitive data may be exposed to unauthorized persons or to the public. A system failure or security breach that interrupts our operations or the operations at one of our third-party vendors or partners could result in intellectual property and other proprietary or confidential information being lost or stolen or a material disruption of our drug development programs and commercial operations. For example, the loss of clinical trial data from ongoing or planned clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. To the extent that any disruption or security breach results in a loss of or damage to our data or applications, loss of trade secrets or inappropriate disclosure of confidential or proprietary information, including protected health information, or personal information of employees or former employees, access to our clinical data, or disruption of the manufacturing process, we could incur liability and the further development of our drug candidates could be delayed. Further, we could incur significant costs to investigate and mitigate such cybersecurity incidents. A security breach that results in the unauthorized access, use or disclosure of personal information also requires us to notify individuals, governmental authorities, credit reporting agencies, or other parties, as applicable, pursuant to privacy and security laws and regulations or other obligations. Such a security breach could harm our reputation, erode confidence in our information security measures, and lead to regulatory scrutiny and result in penalties, fines, indemnification claims, litigation and potential civil or criminal liability.

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We or the third parties upon whom we depend may be adversely affected by earthquakes or other natural disasters and our business continuity and disaster recovery plans may not adequately protect us from a serious disaster.

Our corporate headquarters and one of our laboratories are located in the San Francisco Bay Area, and our collaboration partner for Crysvita, KKC, is located in Japan, which have both in the past experienced severe earthquakes and other natural disasters. We do not carry earthquake insurance. Earthquakes or other natural disasters could severely disrupt our operations or those of our collaborators, and have a material adverse effect on our business, results of operations, financial condition, and prospects. We have also experienced power outages as a result of wildfires in the San Francisco Bay Area which are likely to continue to occur in the future. If a natural disaster, power outage, or other event occurred that prevented us from using all or a significant portion of our headquarters, that damaged critical infrastructure (such as the manufacturing facilities of our third-party contract manufacturers) or that otherwise disrupted operations, it may be difficult or, in certain cases, impossible for us to continue our business for a substantial period of time. The disaster recovery and business continuity plans we have in place currently are limited and may be inadequate in the event of a serious disaster or similar event. We may incur substantial expenses as a result of the limited nature of our disaster recovery and business continuity plans, which, particularly when taken together with our lack of earthquake insurance, could have a material adverse effect on our business.

We may acquire companies or products or engage in strategic transactions, which could divert our management’s attention and cause us to incur various costs and expenses, or result in fluctuations with respect to the value of such investment, which could impact our operating results.

We may acquire or invest in businesses or products that we believe could complement or expand our business or otherwise offer growth opportunities. For example, we acquired Dimension in November 2017 and GeneTx in July 2022. The pursuit of potential acquisitions or investments may divert the attention of management and may cause us to incur various costs and expenses in identifying, investigating, and pursuing them, whether or not they are consummated. We may not be able to identify desirable acquisitions or investments or be successful in completing or realizing anticipated benefits from such transactions. We may experience difficulties in assimilating the personnel, operations and products of the acquired companies, management’s attention may be diverted from other business concerns and we may potentially lose key employees of the acquired company. If we are unable to successfully or timely integrate the operations of acquired companies with our business, we may incur unanticipated liabilities and be unable to realize the revenue growth, synergies and other anticipated benefits resulting from the acquisition, and our business, results of operations and financial condition could be materially and adversely affected.

The value of our investments in other companies or businesses may also fluctuate significantly and impact our operating results quarter to quarter or year to year. We purchased 7,825,797 shares of common stock of Solid in October 2020. Our investment in Solid is being accounted for at fair value, as the fair value is readily determinable. As a result, increases or decreases in the stock price of equity investments have resulted in and will result in accompanying changes in the fair value of our investments, and cause substantial volatility in, our operating results for the reporting period. As the fair value of our investment in Solid is dependent on the stock price of Solid, which has recently seen wide fluctuations, the value of our investments and the impact on our operating results may similarly fluctuate significantly from quarter to quarter and year to year such that period-to-period comparisons may not be a good indication of the future value of the investments and our future operating results.

Risks Related to Ownership of Our Common Stock

The market price of our common stock may be highly volatile.

The market price of our common stock has been, and is likely to continue to be, volatile, including for reasons unrelated to changes in our business. Our stock price could be subject to wide fluctuations in response to a variety of factors, including but not limited to the following:

•adverse results or delays in preclinical or clinical studies;

•any inability to obtain additional funding;

•any delay in filing an IND, NDA, BLA, MAA, or other regulatory submission for any of our product candidates and any adverse development or perceived adverse development with respect to the applicable regulatory agency’s review of that IND, NDA, BLA, MAA, or other regulatory submission;

•the perception of limited market sizes or pricing for our products and product candidates;

•decisions by our collaboration partners with respect to the indications for our products and product candidates in countries where they have the right to commercialize the products and product candidates;

•decisions by our collaboration partners regarding market access and pricing in countries where they have the right to commercialize our products and product candidates;

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•failure to successfully develop and commercialize our products and product candidates;

•the level of revenue we receive from our commercialized products or from named patient sales;

•post-marketing safety issues;

•failure to maintain our existing strategic collaborations or enter into new collaborations;

•failure by us or our licensors and strategic collaboration partners to prosecute, maintain, or enforce our intellectual property rights;

•changes in laws or regulations applicable to our products;

•any inability to obtain adequate product supply for our products and product candidates or the inability to do so at acceptable prices;

•adverse regulatory decisions;

•introduction of new products, services, or technologies by our competitors;

•changes in or failure to meet or exceed financial projections or other guidance we may provide to the public;

•changes in or failure to meet or exceed the financial projections or other expectations of the investment community;

•the perception of the pharmaceutical industry or our company by the public, legislatures, regulators, and the investment community;

•the perception of the pharmaceutical industry’s approach to drug pricing;

•announcements of significant acquisitions, strategic partnerships, joint ventures, or capital commitments by us, our strategic collaboration partners, or our competitors;

•the integration and performance of any businesses we have acquired or may acquire;

•disputes or other developments relating to proprietary rights, including patents, litigation matters, and our ability to obtain patent protection for our technologies;

•additions or departures of key scientific or management personnel;

•significant investigations, regulatory proceedings or lawsuits, including patent or stockholder litigation;

•securities or industry analysts’ reports regarding our stock, or their failure to issue such reports;

•changes in the market valuations of similar companies;

•general market, macroeconomic conditions or geopolitical developments, rising inflation, and the potential recessionary environment;

•sales of our common stock by us or our stockholders in the future; and

•trading volume of our common stock.

In addition, biotechnology and biopharmaceutical companies in particular have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies. Broad market and industry factors may negatively affect the market price of our common stock, regardless of our actual operating performance.

Future sales and issuances of our common stock or rights to purchase common stock, including pursuant to our equity incentive plans, could result in additional dilution of the percentage ownership of our stockholders and could cause our stock price to fall.

We will need additional capital in the future to continue our planned operations. To the extent we raise additional capital by issuing equity securities, our stockholders may experience substantial dilution. We may sell common stock, convertible securities, or other equity securities in one or more transactions at prices and in a manner we determine from time to time. If we sell common stock, convertible securities, or other equity securities in more than one transaction, investors may be materially diluted by subsequent sales. These sales may also result in material dilution to our existing stockholders, and new investors could gain rights superior to our existing stockholders.

In June 2023, we adopted our 2023 Incentive Plan, or the 2023 Plan, which replaced our 2014 Incentive Plan, following stockholder approval of the plan. Pursuant to our 2023 Plan, our management is authorized to grant stock options and other equity-based awards to our employees, directors, and consultants. At December 31, 2023, there were 5,359,901 shares available for future grants under the 2023 Plan.

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Pursuant to our 2014 Employee Stock Purchase Plan, which was amended and restated in June 2023, or the A&R ESPP, eligible employees can acquire shares of our common stock at a discount to the prevailing market price. At December 31, 2023, there were 6,609,795 shares available for issuance under the A&R ESPP.

Our board of directors has adopted an Employment Inducement Plan, which was amended in June 2023, or the Inducement Plan, with a maximum of 850,000 shares available for grant under the plan. At December 31, 2023, there were 130,996 shares available for issuance under the Inducement Plan. If our board of directors elects to increase the number of shares available for future grant under the 2023 Plan, the A&R ESPP, or the Inducement Plan, our stockholders may experience additional dilution, which could cause our stock price to fall.

Provisions in our amended and restated certificate of incorporation and by-laws, as well as provisions of Delaware law, could make it more difficult for a third party to acquire us or increase the cost of acquiring us, even if doing so would benefit our stockholders, or remove our current management.

Our amended and restated certificate of incorporation, amended and restated by-laws, and Delaware law contain provisions that may have the effect of delaying or preventing a change in control of us or changes in our management. Our amended and restated certificate of incorporation and by-laws include provisions that:

•authorize “blank check” preferred stock, which could be issued by our board of directors without stockholder approval and may contain voting, liquidation, dividend, and other rights superior to our common stock;

•create a classified board of directors whose members serve staggered three-year terms;

•specify that special meetings of our stockholders can be called only by our board of directors or the chairperson of our board of directors;

•prohibit stockholder action by written consent;

•establish an advance notice procedure for stockholder approvals to be brought before an annual meeting of our stockholders, including proposed nominations of persons for election to our board of directors;

•provide that our directors may be removed only for cause;

•provide that vacancies on our board of directors may be filled only by a resolution adopted by the board of directors;

•expressly authorize our board of directors to modify, alter or repeal our amended and restated by-laws; and

•require holders of 75% of our outstanding common stock to amend specified provisions of our amended and restated certificate of incorporation and amended and restated by-laws.

These provisions, alone or together, could delay, deter, or prevent hostile takeovers and changes in control or changes in our management.

In addition, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which limits the ability of stockholders owning in excess of 15% of our outstanding voting stock to merge or combine with us. Further, no stockholder is permitted to cumulate votes at any election of directors because this right is not included in our amended and restated certificate of incorporation.

Any provision of our amended and restated certificate of incorporation or amended and restated by-laws or Delaware law that has the effect of delaying or deterring a change in control could limit the opportunity for our stockholders to receive a premium for their shares of our common stock, and could also affect the price that some investors are willing to pay for our common stock.

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Our amended and restated certificate of incorporation provides that the Court of Chancery of the State of Delaware is the sole and exclusive forum for substantially all disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.

Our amended and restated certificate of incorporation provides that the Court of Chancery of the State of Delaware is the sole and exclusive forum for (1) any derivative action or proceeding brought on our behalf, (2) any action asserting a claim of breach of fiduciary duty owed by any of our directors, officers, or other employees to us or to our stockholders, (3) any action asserting a claim against us arising under the Delaware General Corporation Law or under our amended and restated certificate of incorporation or bylaws, or (4) any action against us asserting a claim governed by the internal affairs doctrine. The choice of forum provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers, or other employees, which may discourage such lawsuits against us and our directors, officers, and other employees. Alternatively, if a court were to find the choice of forum provision contained in our amended and restated certificate of incorporation to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could harm our business, operating results and financial condition.

General Risk Factors

If we are unable to maintain effective internal control over financial reporting, investors may lose confidence in the accuracy and completeness of our financial reports and the market price of our stock may decrease.

The Sarbanes-Oxley Act requires, among other things, that we maintain effective internal controls for financial reporting and disclosure controls and procedures. In particular, we are required to perform system and process evaluation and testing of our internal controls over financial reporting to allow management to report on the effectiveness of our internal controls over financial reporting, as required by Section 404(a) of the Sarbanes-Oxley Act. Section 404(b) of the Sarbanes-Oxley Act also requires our independent auditors to attest to, and report on, this management assessment. Ensuring that we have adequate internal controls in place so that we can produce accurate financial statements on a timely basis is a costly and time-consuming effort that will need to be evaluated frequently. If we are not able to comply with the requirements of Section 404 or if we or our independent registered public accounting firm are unable to attest to the effectiveness of our internal control over financial reporting, investors may lose confidence in the accuracy and completeness of our financial reports, the market price of our stock could decline and we could be subject to sanctions or investigations by Nasdaq, the SEC, or other regulatory authorities, which would require additional financial and management resources.

We may incur additional tax liabilities related to our operations.

We have a multinational tax structure and are subject to income tax in the U.S. and various foreign jurisdictions. Our effective tax rate is influenced by many factors including changes in our operating structure, changes in the mix of our earnings among countries, our allocation of profits and losses among our subsidiaries, our intercompany transfer pricing agreements and rules relating to transfer pricing, the availability of U.S. research and development tax credits, and future changes in tax laws and regulations in the U.S. and foreign countries. Significant judgment is required in determining our tax liabilities including management’s judgment for uncertain tax positions. The Internal Revenue Service, other domestic taxing authorities, or foreign taxing authorities may disagree with our interpretation of tax laws as applied to our operations. Our reported effective tax rate and after-tax cash flows may be materially and adversely affected by tax assessments in excess of amounts accrued for our financial statements. This could materially increase our future effective tax rate thereby reducing net income and adversely impacting our results of operations for future periods.

Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited.

We have incurred substantial losses during our history. To the extent that we continue to generate taxable losses, unused taxable losses will, subject to certain limitations, carry forward to offset future taxable income, if any, until such unused losses expire. Under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, or the IRC, if a corporation undergoes an “ownership change,” generally defined as a greater than 50% change (by value) in its equity ownership over a three-year period, the corporation’s ability to use its pre-change net operating loss carryforwards, or NOL carryforwards, and other pre-change tax attributes (such as research tax credits) to offset its post-change income may be limited. An analysis to determine limitations upon our NOL carryforwards and other pre-change tax attributes for ownership changes that have occurred previously has been performed, resulting in a permanent decrease of federal and state NOL carryforwards in the amount of $7.2 million and a permanent decrease in federal research tax credit carryforwards in the amount of $0.2 million. As a result of these decreases and others that may occur as a result of future ownership changes, our ability to use our pre-change NOL carryforwards and other tax attribute carryforwards to offset U.S. federal taxable income and tax liabilities is limited and may become subject to even greater limitations, which could potentially accelerate or permanently increase future federal tax liabilities for us. In addition, there may be

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periods during which the use of state income tax NOL carryforwards and other state tax attribute carryforwards (such as state research tax credits) are suspended or otherwise limited, which could potentially accelerate or permanently increase future state tax liabilities for us.

Litigation may substantially increase our costs and harm our business.

We have been, and may in the future become, party to lawsuits including, without limitation, actions, claims and proceedings in the ordinary course of business relating to our directors, officers, stockholders, intellectual property, and employment matters and policies, which will cause us to incur legal fees and other costs related thereto, including potential expenses for the reimbursement of legal fees of officers and directors under indemnification obligations. The expense of defending against such claims or litigation may be significant and there can be no assurance that we will be successful in any defense. Further, the amount of time that may be required to resolve such claims or lawsuits is unpredictable, and these actions may divert management’s attention from the day-to-day operations of our business, which could adversely affect our business, results of operations, and cash flows. Litigation is subject to inherent uncertainties, and an adverse result in such matters that may arise from time to time could have a material adverse effect on our business, results of operations, and financial condition.

Our business and operations could be negatively affected if we become subject to stockholder activism or hostile bids, which could cause us to incur significant expense, hinder execution of our business strategy and impact our stock price.

Stockholder activism, which takes many forms and arises in a variety of situations, has been increasingly prevalent. Stock price declines may also increase our vulnerability to unsolicited approaches. If we become the subject of certain forms of stockholder activism, such as proxy contests or hostile bids, the attention of our management and our board of directors may be diverted from execution of our strategy. Such stockholder activism could give rise to perceived uncertainties as to our future strategy, adversely affect our relationships with business partners and make it more difficult to attract and retain qualified personnel. Also, we may incur substantial costs, including significant legal fees and other expenses, related to activist stockholder matters. Our stock price could be subject to significant fluctuation or otherwise be adversely affected by the events, risks and uncertainties of any stockholder activism.

Increased scrutiny regarding ESG practices and disclosures could result in additional costs and adversely impact our business and reputation.

Companies across all industries are facing increasing scrutiny relating to their Environmental, Social and Governance, or “ESG,” practices and disclosures and institutional and individual investors are increasingly using ESG screening criteria in making investment decisions. Investors who are focused on ESG matters may seek enhanced ESG disclosures or to implement policies adverse to our business, and there can be no assurances that stockholders will not advocate, via proxy contests, media campaigns or other public or private means, for us to make corporate governance changes or engage in certain corporate actions. Our disclosures on these matters or a failure to satisfy evolving stakeholder expectations for ESG practices and reporting may potentially harm our reputation and impact employee retention and access to capital. In addition, our failure, or perceived failure, to pursue or fulfill our goals, targets, and objectives or to satisfy various reporting standards within the timelines we announce, or at all, could expose us to government enforcement actions and private litigation.

Our ability to achieve any goal or objective, including with respect to environmental and diversity initiatives and compliance with ESG reporting standards, is subject to numerous risks, many of which are outside of our control. Examples of such risks include the availability and cost of technologies and products that meet sustainability and ethical supply chain standards, evolving regulatory requirements affecting ESG standards or disclosures, our ability to recruit, develop, and retain diverse talent in our labor markets, and our ability to develop reporting processes and controls that comply with evolving standards for identifying, measuring and reporting ESG metrics. As ESG best-practices, reporting standards, and disclosure requirements continue to develop, we may incur increasing costs related to maintaining or achieving our ESG goals in addition to ESG monitoring and reporting.

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Item 1B. Unresolved Staff Comments

None.

Item 1C: Cybersecurity

In the ordinary course of our business, we collect, use, store, and transmit digitally large amounts of confidential, financial, sensitive, proprietary, personal, and health-related information. The secure maintenance of this information and our information technology systems is important to our operations and business strategy. To this end, we have implemented processes designed to assess, identify, and manage risks from potential unauthorized occurrences on or through our information technology systems that may result in adverse effects on the confidentiality, integrity, and availability of these systems and the data residing therein. These processes are managed and monitored by a dedicated information technology team, including a Senior Director of Information Security, and is led by our Senior Vice President, Chief Information Officer, or “CIO”. Our processes include mechanisms, controls, technologies, and systems designed to prevent or mitigate data loss, theft, misuse, or other security incidents or vulnerabilities affecting the data and maintain a stable information technology environment. For example, we conduct penetration and vulnerability testing, data recovery testing, security audits, and ongoing risk assessments, including due diligence on and audits of our key technology vendors, and other contractors and suppliers. We also conduct regular employee trainings on cyber and information security, among other topics. In addition, we consult with outside advisors and experts, when appropriate, to assist with assessing, identifying, and managing cybersecurity risks, including to anticipate future threats and trends, and their impact on the Company’s risk environment.

Our CIO, together with our Senior Director of Information Security and other members of the IT leadership team, are responsible for assessing and managing cybersecurity risks. Our CIO has ten years of experience managing information technology and cybersecurity. Our Senior Director of Information Security has over 26 years of experience managing information technology and cybersecurity matters and is certified as a Certified Information Systems Security Professional (CISSP). We consider cybersecurity, along with other significant risks that we face, within our overall enterprise risk management framework. During the year ended December 31, 2023, we did not identify risks from known cybersecurity threats, including as a result of any prior cybersecurity incidents, that have materially affected us, but we face certain ongoing cybersecurity risks or threats that, if realized, are reasonably likely to materially affect us. Additional information on cybersecurity risks we face is discussed in Part I, Item 1A, “Risk Factors,” under the heading “Our business and operations may be materially adversely affected in the event of computer system failures or security breaches.”

The Board of Directors, as a whole and at the committee level, has oversight for the most significant risks facing us and for our processes to identify, prioritize, assess, manage, and mitigate those risks. The Audit Committee, which is comprised solely of independent directors, has been designated by our Board to oversee cybersecurity risks. The Audit Committee receives regular updates on cybersecurity and information technology matters and related risk exposures from our CIO. The Board also receives updates from the Audit Committee on cybersecurity risks on at least an annual basis.

Item 2. Properties

Our primary operations are conducted at the leased facilities summarized in the below table. In 2023, we completed the construction of our gene therapy manufacturing facility located in Bedford, Massachusetts. We believe our facilities are adequate and suitable for our current needs and that we will be able to obtain new or additional leased space in the future when necessary.

Property Location	Use	Lease Expiration Date
Novato, California	Headquarters and office	December 2024
Novato, California	Laboratory and office	October 2028
Brisbane, California	Office	June 2026
Somerville, Massachusetts	Laboratory and office	October 2029
Woburn, Massachusetts	Laboratory and office	April 2025
Woburn, Massachusetts	Laboratory and office	October 2026
Bedford, Massachusetts	Manufacturing facility	Owned property

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Item 3. Legal Proceedings

We are not currently a party to any material legal proceedings. We may, however, in the ordinary course of business face various claims brought by third parties or government regulators and we may, from time to time, make claims or take legal actions to assert our rights, including claims relating to our directors, officers, stockholders, intellectual property rights, employment matters and the safety or efficacy of our products. Any of these claims could subject us to costly litigation and, while we generally believe that we have adequate insurance to cover many different types of liabilities, our insurance carriers may deny coverage, may be inadequately capitalized to pay on valid claims, or our policy limits may be inadequate to fully satisfy any damage awards or settlements. If this were to happen, the payment of any such awards could have a material adverse effect on our consolidated operations, cash flows and financial position. Additionally, any such claims, whether or not successful, could damage our reputation and business.

Item 4. Mine Safety Disclosures

Not applicable.

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PART II

Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities

Our common stock has been traded on The Nasdaq Global Select Market since January 31, 2014 under the symbol “RARE”. As of February 15, 2024, we had 8 holders of record of our common stock. Certain shares are held in “street” name and, accordingly, the number of beneficial owners of such shares is not known or included in the foregoing number.

STOCK PRICE PERFORMANCE GRAPH

The following stock performance graph compares our total stock return with the total return for (i) the Nasdaq Composite Index and (ii) the Nasdaq Biotechnology Index for the period from December 31, 2018 through December 31, 2023. The figures represented below assume an investment of $100 in our common stock at the closing price of $43.48 on December 31, 2018 and in the Nasdaq Composite Index, or IXIC, and the Nasdaq Biotechnology Index, or NBI, on December 31, 2018 and the reinvestment of dividends into shares of common stock. The comparisons in the table are required by the SEC and are not intended to forecast or be indicative of the possible future performance of our common stock. This graph shall not be deemed “soliciting material” or be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or the Exchange Act, or otherwise subject to the liabilities under that section, and shall not be deemed to be incorporated by reference into any of our filings under the Securities Act of 1933, as amended, or the Securities Act, whether made before or after the date hereof and irrespective of any general incorporation language in any such filing.

 

$100 Investment in Stock or Index	Ticker	December 31, 2018		December 31, 2019		December 31, 2020		December 31, 2021		December 31, 2022		December 31, 2023
Ultragenyx Pharmaceutical Inc.	RARE	$	100.00	$	98.23	$	318.38	$	193.40	$	106.55	$	109.98
NASDAQ Composite Index	^IXIC	$	100.00	$	135.23	$	194.24	$	235.78	$	157.74	$	226.24
NASDAQ Biotechnology Index	^NBI	$	100.00	$	124.41	$	156.36	$	155.37	$	138.42	$	143.60

Dividend Policy

We have never declared or paid cash dividends on our common stock. We currently intend to retain all available funds and any future earnings, if any, to fund the development, operation, and expansion of our business, and we do not anticipate paying any cash dividends on our common stock in the foreseeable future. Any future determination to pay dividends will be made at the discretion of our board of directors or any authorized committee thereof.

Unregistered Sales of Equity Securities

None.

Issuer’s Purchases of Equity Securities

None.

Item 6. Reserved

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Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations

MANAGEMENT’S DISCUSSION AND ANALYSIS OF

FINANCIAL CONDITION AND RESULTS OF OPERATIONS

You should read the following discussion and analysis of our financial condition and results of operations together with our Consolidated Financial Statements and related notes included elsewhere in this Annual Report.

This discussion and analysis generally covers our financial condition and results of operations for the year ended December 31, 2023, including year-over-year comparisons versus the year ended December 31, 2022. Our Annual Report on Form 10-K for the year ended December 31, 2022 includes a discussion and analysis of our financial condition and results of operations for the year ended December 31, 2021 in "Part II, Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations.”

Overview

Ultragenyx Pharmaceutical Inc., we or the Company, are a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultrarare genetic diseases. We have built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease. Our strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.

Approved Therapies and Clinical Product Candidates

Our current approved therapies and clinical-stage pipeline consist of four product categories: biologics, small molecules, AAV gene therapy, and nucleic acid product candidates. We have four commercially approved products, consisting of Crysvita® (burosumab) for the treatment of X-linked hypophosphatemia, or XLH, and tumor-induced osteomalacia, or TIO, Mepsevii® (vestronidase alfa) for the treatment of mucopolysaccharidosis VII, or MPSVII or Sly Syndrome, Dojolvi® (triheptanoin) for the treatment of long-chain fatty acid oxidation disorders, or LC-FAOD, and Evkeeza® (evinacumab) for the treatment of homozygous familial hypercholesterolemia, or HoFH. Please see “Item 1. Business” above for a description of our approved products and our clinical stage pipeline products.

Financial Operations Overview

We are a biopharmaceutical company with a limited operating history. To date, we have invested substantially all of our efforts and financial resources in identifying, acquiring, and developing our products and product candidates, including conducting clinical studies and providing selling, general and administrative support for these operations. To date, we have funded our operations primarily from the sale of our equity securities, revenues from our commercial products, the sale of certain future royalties, and strategic collaboration arrangements.

We have incurred net losses in each year since inception. Our net losses were $606.6 million and $707.4 million for the years ended December 31, 2023 and 2022, respectively. Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from selling, general and administrative costs associated with our operations.

For the year ended December 31, 2023, our total revenues increased to $434.2 million, compared to $363.3 million for the same period in 2022. The increase in revenue was driven by higher demand for our approved products.

As of December 31, 2023, we had $777.1 million in available cash, cash equivalents and marketable debt securities.

Critical Accounting Policies and Significant Judgments and Estimates

Our management’s discussion and analysis of our financial condition and results of operations is based on our Consolidated Financial Statements, which have been prepared in accordance with U.S. generally accepted accounting principles, or GAAP. The preparation of these Consolidated Financial Statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements, as well as the reported expenses incurred during the reporting periods. Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. We periodically review our estimates as a result of changes in circumstances, facts and experience. The effects of material revisions in estimates are reflected in the financial statements prospectively from the date of the change in estimate. Our significant accounting policies are more fully described in Note 2 to our financial statements included elsewhere in this Annual Report.

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We define our critical accounting policies as those GAAP accounting principles that require us to make subjective estimates and judgments about matters that are uncertain and are likely to have a material impact on our financial condition and results of operations as well as the specific manner in which we apply those principles. We believe the critical accounting policies used in the preparation of our financial statements that require significant estimates and judgments are as follows:

Accrued Research and Development, and Research and Development Expenses

As part of the process of preparing consolidated financial statements, we are required to estimate and accrue expenses, the largest of which is related to accrued research and development expenses. This process involves reviewing contracts and purchase orders, identifying services that have been performed on our behalf, and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of the actual costs.

We record accruals for estimated costs of research, preclinical and clinical studies, and manufacturing development. These costs are a significant component of our research and development expenses. A substantial portion of our ongoing research and development activities is conducted by third-party service providers. We accrue the costs incurred under our agreements with these third parties based on actual work completed in accordance with agreements established with these third parties. We determine the actual costs through discussions with internal personnel and external service providers as to the progress or stage of completion of the services and the agreed-upon fee to be paid for such services. We make significant judgments and estimates in determining the accrual balance in each reporting period. As actual costs become known, we adjust our accruals. Although we do not expect our estimates to be materially different from amounts actually incurred, our understanding of the status and timing of services performed relative to the actual status and timing of services performed may vary and could result in us reporting amounts that are too high or too low in any particular period. Our accrual is dependent, in part, upon the receipt of timely and accurate reporting from clinical research organizations and other third-party vendors.

Research and development costs are expensed as incurred and consist of salaries and benefits, stock-based compensation, lab supplies, materials and facility costs, as well as fees paid to other nonemployees and entities that conduct certain research and development activities on our behalf. Amounts incurred in connection with collaboration and license agreements are also included in research and development expense. Payments made prior to the receipt of goods or services to be used in research and development are capitalized until the goods or services are received.

To date, there have been no material differences from our accrued estimated expenses to the actual clinical trial expenses; however, due to the nature of estimates, we cannot assure you that we will not make changes to our estimates in the future as we become aware of additional information about the status or conduct of our clinical studies and other research activities.

Revenue Recognition

Product Sales

We sell our approved products through a limited number of distributors. Under ASC 606, revenue from product sales is recognized at the point in time when control is transferred to these distributors. We also recognize revenue from sales of certain products on a “named patient” basis, which are allowed in certain countries prior to the commercial approval of the product. Prior to recognizing revenue, we make estimates of the transaction price, including any variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Product sales are recorded net of estimated government-mandated rebates and chargebacks, estimated product returns, and other deductions.

Provisions for returns and other adjustments are provided for in the period the related revenue is recorded, as estimated by management. These reserves are based on estimates of the amounts earned or to be claimed on the related sales and are reviewed periodically and adjusted as necessary. Our estimates of government mandated rebates, chargebacks, estimated product returns, and other deductions depends on the identification of key customer contract terms and conditions, negotiated pricing, as well as estimates of sales volumes to different classes of payors. If actual results vary, we may need to adjust these estimates, which could have a material effect on earnings in the period of the adjustment.

Collaboration, License and Royalty Revenue

We have certain license and collaboration agreements that are within the scope of Accounting Standards Codification, or ASC, 808, Collaborative Agreements, which provides guidance on the presentation and disclosure of collaborative arrangements. Generally, the classification of the transactions under the collaborative arrangements is determined based on the nature of contractual terms of the arrangement, along with the nature of the operations of the participants. We record our share of collaboration revenue, net of transfer pricing related to net sales in the period in which such sales occur, if we are considered as an

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agent in the arrangement. We are considered an agent when the collaboration partner controls the product before transfer to the customers and has the ability to direct the use of and obtain substantially all of the remaining benefits from the product. Funding received related to research and development services and commercialization costs is generally classified as a reduction of research and development expenses and selling, general and administrative expenses, respectively, in the Consolidated Statement of Operations, because the provision of such services for collaborative partners are not considered to be part of our ongoing major or central operations.

We also record royalty revenues under certain of our license or collaboration agreements in exchange for license of intellectual property.

We utilize certain information from our collaboration partners to record collaboration revenue, including revenue from the sale of the product, associated reserves on revenue, and costs incurred for development and sales activities. For the periods covered in the financial statements presented, there have been no material changes to prior period estimates of revenues and expenses.

We sold the right to receive certain royalty payments from net sales of Crysvita in certain territories to RPI Finance Trust, or RPI, an affiliate of Royalty Pharma, and to OCM LS23 Holdings LP, an investment vehicle for Ontario Municipal Employees Retirement System, or OMERS, as further described in “Liabilities for Sales of Future Royalties” below. We record the royalty revenue from the net sales of Crysvita in the applicable territories on a prospective basis as non-cash royalty revenue in the Consolidated Statements of Operations over the term of the applicable arrangement.

The terms of our collaboration and license agreements may contain multiple performance obligations, which may include licenses and research and development activities. We evaluate these agreements under ASC 606, Revenue from Contracts with Customers, or ASC 606, to determine the distinct performance obligations. We analogize to ASC 606 for the accounting for distinct performance obligations for which there is a customer relationship. Prior to recognizing revenue, we make estimates of the transaction price, including variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Total consideration may include nonrefundable upfront license fees, payments for research and development activities, reimbursement of certain third-party costs, payments based upon the achievement of specified milestones, and royalty payments based on product sales derived from the collaboration.

If there are multiple distinct performance obligations, we allocate the transaction price to each distinct performance obligation based on our relative standalone selling price. The standalone selling price is generally determined based on the prices charged to customers or using expected cost-plus margin. We estimate the efforts needed to complete the performance obligations and recognize revenue by measuring the progress towards complete satisfaction of the performance obligations using input measures.

Inventory

We expense costs associated with the manufacture of our products prior to regulatory approval. Typically, capitalization of such costs begins when we have received the regulatory approval of the product. Prior to the approval of our products by the U.S. Food and Drug Administration, or FDA, manufacturing and related costs are expensed. As of December 31, 2023, we do not hold a material amount of previously expensed inventory for our approved products.

Inventory that is manufactured after regulatory approval is valued at the lower of cost and net realizable value and cost is determined using the average-cost method.

We periodically review our inventories for excess amounts or obsolescence and write down obsolete or otherwise unmarketable inventory to the estimated net realizable value.

Liabilities for Sales of Future Royalties

In December 2019, we entered into a Royalty Purchase Agreement with RPI. Pursuant to the agreement, RPI paid us $320.0 million in consideration for our right to receive royalty payments on the net sales of Crysvita in the European Union, or the EU, the United Kingdom, and Switzerland, effective January 1, 2020, under the terms of our Collaboration and License Agreement with Kyowa Kirin Co., Ltd., or KKC. The agreement with RPI will automatically terminate, and the payment of royalties to RPI will cease, in the event aggregate royalty payments received by RPI are equal to or greater than the capped amount of $608.0 million prior to December 31, 2030, or in the event aggregate royalty payments received by RPI are less than $608.0 million prior to December 31, 2030, when aggregate royalty payments received by RPI are equal to $800.0 million.

In July 2022, we entered into a Royalty Purchase Agreement with OMERS. Pursuant to the agreement, OMERS paid $500.0 million to us in consideration for the right to receive 30% of the future royalty payments due to us from KKC based on net sales of Crysvita in the U.S. and Canada under the terms of the KKC Collaboration Agreement. The calculation of royalty payments to OMERS

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is based on net sales of Crysvita beginning in April 2023 and continuing until expiration, which is the earlier of the date on which aggregate payments received by OMERS equals $725.0 million or the date the final royalty payment is made to us under the KKC Collaboration Agreement.

Proceeds from these transactions were recorded as liabilities (specifically, liabilities for sales of future royalties on the Consolidated Balance Sheets). We are amortizing $320.0 million and $500.0 million, net of transaction costs of $5.8 million and $9.1 million for RPI and OMERS, respectively, using the effective interest method over the estimated life of the applicable arrangement. In order to determine the amortization of the liabilities, we are required to estimate the total amount of future royalty payments to be received by us and paid to RPI and OMERS, subject to the capped amount, over the life of the arrangements. The excess of future estimated royalty payments (subject to the capped amount) to RPI and OMERS, in excess of the net proceeds received of $314.2 million and $491.0 million, respectively, is recorded as non-cash interest expense over the life of the arrangements. Consequently, we estimate an imputed interest on the unamortized portion of the liabilities and record interest expense relating to the transactions. We record the royalty revenue arising from the net sales of Crysvita in the applicable territories as non-cash royalty revenue in the Consolidated Statements of Operations over the term of the arrangements.

We periodically assess the expected royalty payments using a combination of historical results, internal projections and forecasts from external sources. To the extent such payments are greater or less than our initial estimates or the timing of such payments is materially different than its original estimates, we will prospectively adjust the amortization of the liabilities and the effective interest rate. Our effective annual interest rates were 6.2% and 7.8%, for RPI and OMERS, respectively, as of December 31, 2023.

There are a number of factors that could materially affect the amount and timing of royalty payments from KKC in the applicable territories, most of which are not within our control. Such factors include, but are not limited to, the success of KKC’s sales and promotion of Crysvita, changing standards of care, macroeconomic and inflationary pressures, the introduction of competing products, pricing for reimbursement in various territories, manufacturing or other delays, intellectual property matters, adverse events that result in governmental health authority imposed restrictions on the use of Crysvita, significant changes in foreign exchange rates as the royalty payments are made in U.S. dollars, or USD, while significant portions of the underlying sales of Crysvita are made in currencies other than USD, and other events or circumstances that could result in reduced royalty payments from sales of Crysvita, all of which would result in a reduction of non-cash royalty revenue and the non-cash interest expense over the life of the arrangement. Conversely, if sales of Crysvita in the relevant territories are more than expected, the non-cash royalty revenue and the non-cash interest expense recorded by us would be greater over the term of the arrangements.

Stock-Based Compensation

Stock-based compensation costs related to equity awards granted to employees are measured at the date of grant based on the estimated fair value of the award, net of estimated forfeitures. We estimate the grant date fair value of options, and the resulting stock-based compensation expense, using the Black-Scholes option-pricing model. The grant date fair value of the stock-based awards is recognized on a straight-line basis over the requisite service period, which is generally the vesting period of the respective awards. We expect to continue to grant equity awards in the future, and to the extent that we do, our actual stock-based compensation expense will likely increase. The Black-Scholes option-pricing model requires the use of certain subjective assumptions which determine the estimated fair value of stock-based awards.

•Expected Term — The expected term represents the period that the stock-based awards are expected to be outstanding and is determined using the simplified method (based on the midpoint between the vesting date and the end of the contractual term).

•Expected Volatility— The expected volatility is based on historical volatility over the look-back period corresponding to the expected term.

Strike price for options, including performance stock options, or PSOs, is equal to the closing market value of our common stock on the date of grant.

In addition to the assumptions used in the Black-Scholes option-pricing model, we also estimate a forfeiture rate to calculate the stock-based compensation for our awards. We will continue to use judgment in evaluating the expected volatility, expected terms, and forfeiture rates utilized for our stock-based compensation calculations on a prospective basis and will revise in subsequent periods, if actual forfeitures differ from those estimates.

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For restricted stock units, or RSUs, and performance stock units, or PSUs, the fair value is based on the market value of our common stock on the date of grant, except for certain PSUs with a market vesting condition, for which fair value is estimated using a Monte Carlo simulation model. Stock-based compensation expense for RSUs is recognized on a straight-line basis over the requisite service period. PSUs are subject to vest only if certain specified criteria are achieved and the employees’ continued service with the Company. For certain PSUs, the number of PSUs that may vest are also subject to the achievement of certain specified criteria, including both performance conditions and market conditions. Compensation expense for PSUs is recognized only after the achievement of the specified criteria is considered probable and recognized on a straight-line basis between the grant date and the expected vest date, with a catch-up for previously unrecognized expense, if any, recognized in the period the achievement criteria is deemed probable.

For the years ended December 31, 2023, 2022, and 2021 stock-based compensation expense was $135.2 million, $130.4 million, and $105.0 million, respectively. As of December 31, 2023, we had $219.8 million of total unrecognized stock-based compensation costs, net of estimated forfeitures, which we expect to recognize over a weighted-average period of 2.2 years.

Income Taxes

We use the liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are determined based on the differences between the financial reporting and the tax bases of assets and liabilities and are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. We assess the likelihood that the resulting deferred tax assets will be realized. A valuation allowance is provided when it is more likely than not that some portion or all of a deferred tax asset will not be realized.

In conjunction with the acquisition of Dimension Therapeutics, or Dimension, in 2017, we recorded a deferred tax liability reflecting the tax impact of the difference between the book basis and tax basis of acquired IPR&D. Such deferred income tax liability was not used to offset deferred tax assets when analyzing our valuation allowance as the acquired IPR&D is considered to have an indefinite life until we complete or abandon development of the acquired IPR&D.

We recognize benefits of uncertain tax positions if it is more likely than not that such positions will be sustained upon examination based solely on their technical merits, as the largest amount of benefit that is more likely than not to be realized upon the ultimate settlement. Our policy is to recognize interest and penalties related to the underpayment of income taxes as a component of income tax expense or benefit. To date, there have been no interest or penalties charged in relation to the unrecognized tax benefits.

As of December 31, 2023, our total gross deferred tax assets were $1,041.8 million. Due to our lack of earnings history and uncertainties surrounding our ability to generate future taxable income, the net deferred tax assets have been fully offset by a valuation allowance. The deferred tax assets were primarily comprised of federal and state tax net operating losses and tax credit carryforwards. Utilization of the net operating loss and tax credit carryforwards may be subject to an annual limitation due to historical or future ownership percentage change rules provided by the Internal Revenue Code of 1986, and similar state provisions. The annual limitation may result in the expiration of certain net operating loss and tax credit carryforwards before their utilization.

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Results of Operations

Comparison of Years Ended December 31, 2023 and 2022

Revenues (dollars in thousands)

	Year Ended December 31,				Dollar			Percent
	2023		2022		Change			Change
Product sales:
Crysvita	$	75,697	$	42,678	$	33,019		77%
Mepsevii		30,441		20,637		9,804		48%
Dojolvi		70,633		55,612		15,021		27%
Evkeeza		3,642		—		3,642		*
Total product sales		180,413		118,927		61,486		52%
Crysvita royalty revenue		182,652		21,692		160,960		742%
Collaboration and license revenue:
Crysvita collaboration revenue in Profit-Share     Territory		69,705		215,024		(145,319	)	-68%
Daiichi Sankyo		1,479		7,686		(6,207	)	-81%
Total collaboration and license revenue		71,184		222,710		(151,526	)	-68%
Total revenues	$	434,249	$	363,329	$	70,920		20%
* not meaningful

Our product sales increased $61.5 million for the year ended December 31, 2023, compared to the same period in 2022. The increase was primarily due to an increase in demand for Crysvita in Latin America resulting from an increase in the number of patients on therapy, continued increase in demand for our other approved products, and increases in revenue under our named patient programs.

Our Crysvita collaboration revenue in the Profit-Share Territory and royalty revenue increased by a net $15.6 million for the year ended December 31, 2023, compared to the same period in 2022; this increase in Crysvita revenue is primarily due to an increase in the number of patients on therapy. We transitioned commercial responsibilities to KKC in the Profit-Share Territory in April 2023. Post transition, we recognize our revenue share for Crysvita sales in the Profit-Share Territory as royalty revenue, which was recorded as collaboration revenue prior to the transition.

Our revenue from the Daiichi Sankyo arrangement decreased by $6.2 million for the year ended December 31, 2023, compared to the same period in 2022. The decrease was due to the completion of the technology transfer and the technology transfer period as of March 31, 2023.

Cost of Sales (dollars in thousands)

	Year Ended December 31,				Dollar		Percent
	2023		2022		Change		Change
Cost of sales	$	45,209	$	28,320	$	16,889	60%

Cost of sales increased by $16.9 million for the year ended December 31, 2023, compared to the same period in 2022. The increase in cost of sales was due to increased demand for our approved products, partially offset by a decrease in the Crysvita transfer price on sales of the product in Latin America from 35% prior to December 31, 2022, to 30% in 2023.

Research and Development Expenses (dollars in thousands)

Research and development expenses include internal and external costs incurred for research and development of our programs and program candidates and expenses related to certain technology that we acquire or license through business development transactions. These expenses consist primarily of clinical studies performed by contract research organizations, manufacturing of drug substance and drug product performed by contract manufacturing organizations and at our gene therapy manufacturing facility, materials and supplies, fees from collaborative and other arrangements including milestones, licenses and other fees, personnel costs including salaries, benefits and stock-based compensation, and overhead allocations consisting of various support and infrastructure costs.

Clinical programs include study conduct and manufacturing costs related to clinical program candidates. Translational research includes costs for preclinical study work and costs related to preclinical programs prior to IND filing. Upfront license, acquisition, and milestone fees include any significant expenses related to strategic licensing agreements. Approved products include costs for disease monitoring programs for post-marketing clinical studies, medical affairs activities to support scientific discovery efforts on

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existing programs, and regulatory costs for unapproved regions. Infrastructure costs include direct costs related to laboratory, IT, and equipment depreciation costs, and overhead allocations for human resources, IT, and other allocable costs.

The following table provides a breakout of our research and development expenses by major program type and business activities:

	Year Ended December 31,				Dollar			Percent
	2023		2022		Change			Change
Clinical programs:
Gene therapy programs	$	168,705	$	153,754	$	14,951		10%
Biologic and nucleic acid programs		108,914		97,268		11,646		12%
Translational research		71,820		81,431		(9,611	)	-12%
Upfront license, acquisition, and milestone fees		9,000		75,033		(66,033	)	-88%
Approved products		53,478		75,683		(22,205	)	-29%
Infrastructure		78,929		71,657		7,272		10%
Stock-based compensation		74,531		74,464		67		0%
Other research and development		83,072		76,499		6,573		9%
Total research and development expenses	$	648,449	$	705,789	$	(57,340	)	-8%

Total research and development expenses decreased $57.3 million for the year ended December 31, 2023 compared to the same period in 2022. The change in research and development expenses was due to:

•for gene therapy programs, an increase of $15.0 million, primarily related to the addition of the development costs for the UX111 program acquired from Abeona Therapeutics in May 2022, and an increase in production materials purchases for internal manufacturing, partially offset by decreases in external clinical manufacturing expenses for DTX401;

•for biologic and nucleic acid programs, an increase of $11.6 million, primarily related to the continued clinical progress of the UX143 and GTX102 programs and associated clinical development and manufacturing expenses, partially offset by a reduction in development expense on UX053 for the treatment of Glycogen Storage Disease Type III;

•for translational research, a decrease of $9.6 million, primarily related to decreases in manufacturing and headcount expense for IND-stage projects;

•for upfront license, acquisition, and milestone fees, a decrease of $66.0 million, due to $9.0 million related to payment for achievement of a clinical enrollment milestone for the UX143 program recognized during the year ended December 31, 2023, as compared to $75.0 million recognized from the GeneTx acquisition for the year ended December 31, 2022;

•for approved products, a decrease of $22.2 million, primarily due to transition of Crysvita commercialization responsibilities in North America to KKC and realized cost efficiencies for Dojolvi, partially offset by reimbursement of Regeneron collaboration expenses and increased personnel and launch costs for Evkeeza;

•for infrastructure, an increase of $7.3 million, primarily related to increased expenses for support of our clinical and research program pipeline, expansion of laboratory space, depreciation of laboratory-related leasehold improvements and equipment, and IT-related expenses; and

•for other research and development expenses, an increase of $6.6 million, primarily related to increased staffing and material costs to support internal manufacturing and increased administrative and general support.

We expect our annual research and development expenses to continue to moderate in the future as we advance our product candidates through clinical development. The timing and amount of expenses incurred will depend largely upon the outcomes of current or future clinical studies for our product candidates as well as the related regulatory requirements, manufacturing costs, and any costs associated with the advancement of our preclinical programs.

Selling, General and Administrative Expenses (dollars in thousands)

	Year Ended December 31,				Dollar		Percent
	2023		2022		Change		Change
Selling, general and administrative	$	309,799	$	278,139	$	31,660	11%

Selling, general and administrative expenses increased $31.7 million for the year ended December 31, 2023, compared to the same period in 2022. The increases in selling, general and administrative expenses were primarily due to increases in commercialization costs, and professional services costs, as well as a one-time legal settlement of $6.2 million for the year ended December 31, 2023.

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We expect selling, general and administrative expenses to continue to moderate in the future as we continue to support our approved products and multiple clinical-stage product candidates, with expected decreases in commercial activities due to transition of Crysvita commercial responsibilities to our partner in the Profit-Share Territory.

Interest Income (dollars in thousands)

	Year Ended December 31,				Dollar		Percent
	2023		2022		Change		Change
Interest income	$	26,688	$	11,074	$	15,614	141%

Interest income increased $15.6 million for the year ended December 31, 2023 compared to the same period in 2022, primarily due to increases in interest rates.

Change in Fair Value of Equity Investments (dollars in thousands)

	Year Ended December 31,					Dollar		Percent
	2023		2022			Change		Change
Change in fair value of equity investments	$	397	$	(19,299	)	$	19,696	(102%)

For the year ended December 31, 2023, we recorded a net increase in the fair value of our equity investments of $0.4 million due to an increase in the fair value of our investments in Solid Biosciences Inc., or Solid, common stock for the period.

For the year ended December 31, 2022, we recorded a net decrease in the fair value of our equity investments of $19.3 million. The fair value of our investments in Arcturus Therapeutics Holdings Inc., or Arcturus, and Solid common stock decreased by $8.4 million and $10.9 million, respectively, for the period. The change in fair value of Arcturus included a realized gain on the sale of all our remaining shares of common stock for net proceeds of $10.1 million. As of December 31, 2022, we had sold all our remaining equity investments in Arcturus.

Non-cash Interest Expense on Liabilities for Sales of Future Royalties (dollars in thousands)

	Year Ended December 31,				Dollar		Percent
	2023		2022		Change		Change
Non-cash interest expense on liabilities for     sales of future royalties	$	66,004	$	43,015	$	22,989	53%

Our non-cash interest expense on liabilities for sales of future royalties increased by $23.0 million for the year ended December 31, 2023, compared to the same period in 2022. This was primarily due to the partial sale of North American Crysvita royalties to OMERS in July 2022, with a full year of interest expense in 2023. To the extent the royalty payments are greater or less than our initial estimates or the timing of such payments is materially different than our original estimates, we prospectively adjust the effective interest rate.

Other Expense (dollars in thousands)

	Year Ended December 31,						Dollar		Percent
	2023			2022			Change		Change
Other expense	$	(337	)	$	(1,566	)	$	1,229	(78%)

Other expense decreased $1.2 million for the year ended December 31, 2023, compared to the same period in 2022. These changes were primarily due to fluctuations in foreign exchange rates.

Benefit from (provision for) income taxes

	Year Ended December 31,					Dollar		Percent
	2023		2022			Change		Change
Benefit from (provision for) income taxes	$	1,825	$	(5,696	)	$	7,521	(132%)

For the year ended December 31, 2023, we recognized an income tax benefit of $4.8 million attributable to modifications in our state apportionment methodology. We realized no benefit for current year losses due to a full valuation allowance against the U.S. net deferred tax assets. The benefit was offset by an income tax expense of $3.0 million from foreign jurisdictions.

Beginning in 2022, the Tax Cuts and Jobs Act of 2017 eliminated the right to deduct research and development expenditures for tax purposes in the period the expenses were incurred and instead requires all U.S. and foreign research and development expenditures to be amortized over five and fifteen tax years, respectively. Due to this required capitalization of research and

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development expenditures and the significant taxable income generated as a result of our sale of royalties in July 2022, we recorded a one-time discrete tax expense of $6.1 million for the year ended December 31, 2022. The discrete tax expense is for state taxes we anticipate paying as a result of statutory limitations on our ability to offset expected taxable income with net operating loss carry forwards in certain states. We realized no benefit for current year losses due to a full valuation allowance against the U.S. net deferred tax assets.

Liquidity and Capital Resources

To date, we have funded our operations primarily from the sale of our equity securities, revenue from our commercial products, the sale of certain future royalties, and strategic collaboration arrangements.

As of December 31, 2023, we had $777.1 million in available cash, cash equivalents, and marketable debt securities. We believe that our existing capital resources will be sufficient to fund our projected operating requirements for at least the next twelve months. Our cash, cash equivalents, and marketable debt securities are held in a variety of deposit accounts, interest-bearing accounts, corporate bond securities, commercial paper, U.S government securities, asset-backed securities, and money market funds. Cash in excess of immediate requirements is invested with a view toward liquidity and capital preservation, and we seek to minimize the potential effects of concentration and credit risk.

In October 2023, we completed an underwritten public offering in which 9,833,334 shares of common stock were sold, including the exercise in full by the underwriters of their option to purchase an additional 1,500,000 shares, at a public offering price of $30.00 per share. In connection with the offering, we sold to certain investors pre-funded warrants, in lieu of common stock, to purchase 1,666,722 shares of common stock at a purchase price of $29.999 per pre-funded warrant, which equals the public offering price per share of common stock less the $0.001 exercise price per share of each pre-funded warrant. The total proceeds that we received from the offering were $326.5 million, net of underwriting discounts and commissions.

In May 2021, we entered into an Open Market Sale Agreement with Jefferies LLC, or Jefferies, pursuant to which we may offer and sell shares of our common stock having an aggregate offering proceeds up to $350.0 million, from time to time, in at-the-market, or ATM, offerings through Jefferies. There were 1,175,584 shares sold under this arrangement for the year ended December 31, 2023, for net proceeds of $53.3 million. No shares were sold under this arrangement for the year ended December 31, 2022. As of December 31, 2023, net proceeds from shares sold under the arrangement were $132.2 million.

The following table summarizes our cash flows for the periods indicated (in thousands):

	Year Ended December 31,
	2023			2022
Cash used in operating activities	$	(474,806	)	$	(380,465	)
Cash provided by (used in) investing activities		168,000			(291,652	)
Cash provided by financing activities		388,142			501,208
Effect of exchange rate changes on cash		462			(1,075	)
Net increase (decrease) in cash, cash equivalents, and    restricted cash	$	81,798		$	(171,984	)

Cash Used in Operating Activities

Our primary use of cash is to fund operating expenses, which consist primarily of research and development and commercial expenditures. Due to our significant research and development expenditures, we have generated significant operating losses since our inception. Cash used to fund operating expenses is affected by the timing of when we pay these expenses, as reflected in the change in our outstanding accounts payable and accrued expenses.

Cash used in operating activities for the year ended December 31, 2023 was $474.8 million and primarily reflected a net loss of $606.6 million, partially offset by non-cash items of $146.9 million, net, which consisted primarily of non-cash collaboration royalty revenues, interest expense related to the sale of future royalties to RPI and OMERS, net of amounts capitalized, stock-based compensation, amortization of discounts on marketable debt securities, and depreciation and amortization. The change in operating assets and liabilities also reflected a net use of cash of $15.1 million, primarily due to an increase in accounts receivable primarily related to an increase in sales of our approved products, partially offset by a net decrease in other assets primarily in prepaid manufacturing.

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Cash used in operating activities for the year ended December 31, 2022 was $380.5 million and reflected a net loss of $707.4 million partially offset by non-cash items of $266.7 million, net, which consisted primarily of non-cash collaboration royalty revenues, interest expense related to the sale of future royalties to RPI and OMERS, net of amounts capitalized, stock-based compensation, acquired in-process research and development relating to our acquisition of GeneTx, the change in fair value of equity investments, primarily for the net change in fair value of equity investments from Arcturus and Solid, and depreciation and amortization. The change in operating assets and liabilities also reflected net cash provided of $60.2 million, primarily due to an increase in accounts payable, accrued, and other liabilities, primarily due to timing of payments and receipt of invoices, as well as an increase in manufacturing accruals related to manufacturing and clinical expenses, an increase in accrued bonus due to an increase in headcount, and an increase in accrued development costs owed to a collaboration partner, partially offset by an increase in accounts receivable primarily related to an increase in sales of our approved products.

Cash Provided by (Used in) Investing Activities

Cash provided by investing activities for the year ended December 31, 2023 was $168.0 million and was primarily related to $219.8 million from net activities in marketable debt securities, offset by purchases of property, plant, and equipment of $44.3 million, primarily related to the fit-out of our gene therapy manufacturing facility.

Cash used in investing activities for the year ended December 31, 2022 was $291.7 million and was primarily related to purchases of property, plant, and equipment of $116.1 million, primarily related to the construction of our gene therapy manufacturing facility, the acquisition of GeneTx for $75.0 million, net of cash acquired, $79.8 million from net activities in marketable debt securities, and the payment to Regeneron for intangible assets of $30.0 million, offset by proceeds from the sale of Arcturus common stock of $10.1 million.

Cash Provided by Financing Activities

Cash provided by financing activities for the year ended December 31, 2023 was $388.1 million and was primarily comprised of $326.5 million in net proceeds from the sale of common stock in our October 2023 underwritten public offering and $53.3 million in net proceeds from the issuance of common stock from our ATM.

Cash provided by financing activities for the year ended December 31, 2022 was $501.2 million and was primarily comprised of $491.0 million in net proceeds from the partial sale of future North America Crysvita royalties to OMERS and $10.8 million in net proceeds from the issuance of common stock upon the exercise of stock options, net of taxes withheld from the vesting of restricted stock units.

Funding Requirements

We anticipate that, excluding non-recurring items, we will continue to generate annual losses for the foreseeable future as we continue the development of, and seek regulatory approvals for, our product candidates, and continue with commercialization of approved products. We may require additional capital to fund our operations, to complete our ongoing and planned clinical studies, to commercialize our products, to continue investing in early-stage research capabilities to promote our pipeline growth, to continue to acquire or invest in businesses or products that complement or expand our business, including future milestone payments thereunder, and to further develop our general infrastructure and such funding may not be available to us on acceptable terms or at all.

If we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we may be required to delay, limit, reduce the scope of, or terminate one or more of our clinical studies, research and development programs, future commercialization efforts, or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

Our future funding requirements will depend on many factors, including the following:

•the scope, rate of progress, results and cost of our clinical studies, nonclinical testing, and other related activities;

•the cost of manufacturing clinical supplies, and establishing commercial supplies, of our product candidates, products that we have begun to commercialize, and any products that we may develop in the future;

•the cost of operating our GMP gene therapy manufacturing facility;

•the number and characteristics of product candidates that we pursue;

•the cost, timing, and outcomes of regulatory interactions and approvals;

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•the cost and timing of establishing our commercial infrastructure, and distribution capabilities;

•the impact of macroeconomic conditions, including the general economic slowdown, inflationary pressure, high interest rates, a potential U.S. federal government shutdown, and potential recessionary environment on our business operations and operating results, as described in “Part I, Item IA. Risk Factors " and

•the terms and timing of any collaborative, licensing, marketing, distribution, acquisition and other arrangements that we may establish, including any required upfront milestone, royalty, reimbursements or other payments thereunder.

We expect to satisfy future cash needs through existing capital balances, revenue from our commercial products, and a combination of public or private equity offerings, debt financings, collaborations, strategic alliances, licensing arrangements, and other marketing and distribution arrangements. Please see “Risk Factors—Risks Related to Our Financial Condition and Capital Requirements.”

Contractual Obligations and Commitments

Material contractual obligations arising in the normal course of business primarily consist of operating and finance leases and manufacturing and service contract obligations. See Note 9 to the Consolidated Financial Statements for amounts outstanding for operating and finance leases on December 31, 2023.

Manufacturing and service contract obligations primarily relate to manufacturing of inventory for our approved products, the majority of which are due in the next 12 months. See Note 15 to the Consolidated Financial Statements for these contractual obligations.

The terms of certain of our licenses, royalties, development and collaboration agreements, as well as other research and development activities, require us to pay potential future milestone payments based on product development success. The amount and timing of such obligations are unknown or uncertain. These potential obligations are further described in Note 8 to the Consolidated Financial Statements.

Recent Accounting Pronouncements

None.

Item 7A. Quantitative and Qualitative Disclosures about Market Risk

Interest Rate Risk

Our exposure to market risk for changes in interest rates relates primarily to interest earned on our cash equivalents and marketable debt securities. The primary objective of our investment activities is to preserve our capital to fund operations. A secondary objective is to maximize income from our investments without assuming significant risk. Our investment policy provides for investments in low-risk, investment-grade debt instruments. As of December 31, 2023, we had cash, cash equivalents, and marketable debt securities totaling $777.1 million, which included bank deposits, money market funds, U.S. government treasury and agency securities, and investment-grade corporate bond securities which are subject to default, changes in credit rating, and changes in market value. The securities in our investment portfolio are classified as available for sale and are subject to interest rate risk and will decrease in value if market interest rates increase. A hypothetical 100 basis point change in interest rates during any of the periods presented would not have had a material impact on the fair market value of our cash equivalents and marketable debt securities as of December 31, 2023. To date, we have not experienced a loss of principal on any of our investments and as of December 31, 2023, we did not record any allowance for credit loss from our investments.

Foreign Currency Risk

We face foreign exchange risk as a result of entering into transactions denominated in currencies other than U.S. dollars. Due to the uncertain timing of expected payments in foreign currencies, we do not utilize any forward exchange contracts. All foreign transactions settle on the applicable spot exchange basis at the time such payments are made. Volatile market conditions arising from the macroeconomic environment (including financial conditions affecting the banking system and financial institutions), inflation, or global political instability may result in significant changes in exchange rates, and in particular a weakening of foreign currencies relative to the U.S. dollar may negatively affect our revenue and operating income as expressed in U.S. dollars. An adverse movement in foreign exchange rates could have a material effect on payments made to foreign suppliers and payments related to license agreements. For the year ended December 31, 2023, a majority of our revenue, expenses, and capital expenditures were denominated in U.S. dollars. A hypothetical 10% change in foreign exchange rates during any of the periods presented would not have had a material impact on our Consolidated Financial Statements.

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Item 8. Financial Statements and Supplementary Data

Our financial statements are annexed to this Annual Report beginning on page F-1 and are incorporated by reference into this Item 8.

Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure

None.

Item 9A. Controls and Procedures

Evaluation of Disclosure Controls and Procedures

Management carried out an evaluation, under the supervision and with the participation of our Principal Executive Officer and our Principal Financial Officer, of the effectiveness of our “disclosure controls and procedures” as of the end of the period covered by this Annual Report, pursuant to Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, or the Exchange Act. In connection with that evaluation, our Principal Executive Officer and our Principal Financial Officer concluded that our disclosure controls and procedures were effective and designed to provide reasonable assurance that the information required to be disclosed is recorded, processed, summarized, and reported within the time periods specified in the SEC rules and forms as of December 31, 2023. For the purpose of this review, disclosure controls and procedures means controls and procedures designed to ensure that information required to be disclosed by us in the reports that we file or submit is recorded, processed, summarized and reported within the time periods specified in the SEC’s rules and forms. These disclosure controls and procedures include, without limitation, controls and procedures designed to ensure that information required to be disclosed by us in the reports that we file or submit is accumulated and communicated to management, including our Principal Executive Officer and our Principal Financial Officer, as appropriate to allow timely decisions regarding required disclosure. In designing and evaluating the disclosure controls and procedures, our management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving the desired control objectives, and our management necessarily applies its judgment in evaluating the cost-benefit relationship of possible controls and procedures.

Management’s Annual Report on Internal Control Over Financial Reporting

Management is responsible for establishing and maintaining adequate internal control over financial reporting as defined in Rules 13a-15(f) and 15d-15(f) of the Exchange Act. Our management used the Committee of Sponsoring Organizations of the Treadway Commission Internal Control - Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework), or the COSO framework, to evaluate the effectiveness of internal control over financial reporting. Management believes that the COSO framework is a suitable framework for its evaluation of financial reporting because it is free from bias, permits reasonably consistent qualitative and quantitative measurements of our internal control over financial reporting, is sufficiently complete so that those relevant factors that would alter a conclusion about the effectiveness of our internal control over financial reporting are not omitted and is relevant to an evaluation of internal control over financial reporting.

Management has assessed the effectiveness of our internal control over financial reporting as of December 31, 2023, and has concluded that as of such date, our internal control over financial reporting was effective.

Our independent registered public accounting firm, Ernst & Young LLP, has audited the financial statements included in this Annual Report and has issued a report on the effectiveness of our internal control over financial reporting. The report of Ernst & Young LLP is included below.

Changes in Internal Control over Financial Reporting

There have been no changes in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act) during our fourth quarter ended December 31, 2023, that have materially affected, or are reasonably likely to materially affect our internal control over financial reporting.

Report of Independent Registered Public Accounting Firm

To the Stockholders and the Board of Directors of Ultragenyx Pharmaceutical Inc.

Opinion on Internal Control Over Financial Reporting

We have audited Ultragenyx Pharmaceutical Inc.’s internal control over financial reporting as of December 31, 2023, based on criteria established in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations of the

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Treadway Commission (2013 framework) (the COSO criteria). In our opinion, Ultragenyx Pharmaceutical Inc. (the Company) maintained, in all material respects, effective internal control over financial reporting as of December 31, 2023, based on the COSO criteria.

We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the consolidated balance sheets of the Company as of December 31, 2023 and 2022, the related consolidated statements of operations, comprehensive loss, stockholders’ equity and cash flows for each of the three years in the period ended December 31, 2023, and the related notes and our report dated February 21, 2024 expressed an unqualified opinion thereon.

Basis for Opinion

The Company’s management is responsible for maintaining effective internal control over financial reporting and for its assessment of the effectiveness of internal control over financial reporting included in the accompanying Management’s Annual Report on Internal Control Over Financial Reporting. Our responsibility is to express an opinion on the Company’s internal control over financial reporting based on our audit. We are a public accounting firm registered with the PCAOB and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audit in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether effective internal control over financial reporting was maintained in all material respects.

Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, testing and evaluating the design and operating effectiveness of internal control based on the assessed risk, and performing such other procedures as we considered necessary in the circumstances. We believe that our audit provides a reasonable basis for our opinion.

Definition and Limitations of Internal Control Over Financial Reporting

A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. A company’s internal control over financial reporting includes those policies and procedures that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in accordance with authorizations of management and directors of the company; and (3) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect on the financial statements.

Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.

/s/ Ernst & Young LLP

San Mateo, California

February 21, 2024

Item 9B. Other Information

On November 10, 2023, Corsee Sanders, Ph.D., a member of the Company’s Board of Directors, adopted a trading arrangement intended to satisfy the affirmative defense of Rule 10b5-1(c), to sell up to 2,322 shares of the Company’s common stock through July 12, 2024, subject to certain conditions.

On December 7, 2023, Matthew Fust, a member of the Company’s Board of Directors, adopted a trading arrangement intended to satisfy the affirmative defense of Rule 10b5-1(c), to sell up to 12,195 shares of the Company’s common stock through December 6, 2024, subject to certain conditions.

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections

Not applicable.

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PART III

Item 10. Directors, Executive Officers and Corporate Governance

Except as set forth below, the information required by this Item is incorporated herein by reference to information in the proxy statement for our 2024 Annual Meeting of Stockholders, which we will file with the SEC within 120 days of the end of the fiscal year to which this Annual Report relates, or the “2024 Proxy Statement”, including under the headings “Nominees and Incumbent Directors,” “Executive Officers,” ““Board of Directors and Committees,” and, as applicable, “Delinquent Section 16(a) Beneficial Ownership Reports.” We have adopted a code of ethics that applies to all of our directors, officers and employees, including our principal executive, principal financial and principal accounting officers, or persons performing similar functions, or Code of Ethics. Our Code of Ethics is posted on our website located at https://ir.ultragenyx.com/ under “Corporate Governance”. We intend to disclose future amendments to certain provisions of the Code of Ethics, and waivers of the Code of Ethics granted to executive officers and directors, on the website within four business days following the date of the amendment or waiver.

Item 11. Executive Compensation

The information required by this Item is incorporated herein by reference to information in the 2024 Proxy Statement, including under the headings “Executive Compensation,” “Director Compensation,” and “Board of Directors and Committees.”

Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters

The information required by this Item is incorporated herein by reference to information in the 2024 Proxy Statement, including under the headings “Security Ownership of Certain Beneficial Owners and Management” and “Equity Compensation Plan Information.”

Item 13. Certain Relationships and Related Transactions, and Director Independence

The information required by this Item is incorporated herein by reference to information in the 2024 Proxy Statement, including under the headings “Certain Relationships and Related-Person Transactions,” “Corporate Governance,” and “Board of Directors and Committees.”

Item 14. Principal Accountant Fees and Services

The information required by this Item is incorporated herein by reference to information in the 2024 Proxy Statement, including under the heading “Proposal No. 3—Ratification of the Selection of Independent Registered Public Accounting Firm.”

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PART IV

Item 15. Exhibits and Financial Statement Schedules

(a) The following documents are filed as part of this Annual Report.

(1) Consolidated Financial Statements

Consolidated Financial Statements—See Index to Consolidated Financial Statements at page F-1 of this Annual Report.

(2) Consolidated Financial Statement Schedules

Consolidated Financial Statement schedules have been omitted in this Annual Report because they are not applicable, not required under the instructions, or the information requested is set forth in the Consolidated Financial Statements or related notes thereto.

(b) Exhibits

Exhibit		Incorporated by Reference			Filed
Number	Exhibit Description	Form	Date	Number	Herewith
3.1	Amended and Restated Certificate of Incorporation	8-K	2/5/2014	3.1
3.2	Second Amended and Restated Bylaws	8-K	12/21/2023	3.1
4.1	Form of Common Stock Certificate	S-1	11/8/2013	4.2
4.2	Form of Indenture	S-3 ASR	2/12/2021	4.2
4.3	Form of Pre-Funded Warrant	8-K	10/23/2023	4.1
4.4	Description of Common Stock	10-K	2/14/2020	4.3
10.1*	Collaboration and License Agreement, effective as of August 29, 2013, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd.	S-1/A	12/23/2013	10.1
10.2	Amendment No. 1 to Collaboration and License Agreement, effective as of August 24, 2015, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd.	10-Q	11/10/2015	10.2
10.3	Amendment No. 2 to Collaboration and License Agreement, effective as of November 28, 2016, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd.	10-K	2/21/2018	10.3
10.4*	Amendment No. 3 to Collaboration and License Agreement, effective September 29, 2017, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd.	10-K	2/21/2018	10.4
10.5*	Amendment No. 4 to Collaboration and License Agreement, effective as of January 29, 2018, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd.	10-K	2/21/2018	10.5
10.6*	Amendment No. 5 to Collaboration and License Agreement, effective as of April 30, 2018, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd.	10-Q	8/3/2018	10.1
10.7*	Amendment No. 6 to Collaboration and License Agreement, effective as of February 1, 2019, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd.	10-Q	5/7/2019	10.2

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10.8*	Amendment No. 7 to Collaboration and License Agreement, effective as of December 5, 2018, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd.	10-Q	5/7/2019	10.3
10.9*	Amendment No. 8 to Collaboration and License Agreement, effective as of July 4, 2019, between Ultragenyx Pharmaceutical Inc. and Kyowa Kirin Co., Ltd. (formerly, Kyowa Hakko Kirin Co., Ltd.)	10-Q	8/2/2019	10.1
10.10*	Amendment No. 9 to Collaboration and License Agreement, effective December 23, 2019, between Ultragenyx Pharmaceutical Inc. and Kyowa Kirin Co., Ltd.	10-K	2/14/2020	10.10
10.11*	Amendment No. 10 to Collaboration and License Agreement, effective as of April 1, 2020, between Ultragenyx Pharmaceutical Inc. and Kyowa Kirin Co., Ltd.	10-Q	5/7/2020	10.2
10.12*	Amendment No. 11 to Collaboration and License Agreement, effective as of December 17, 2021 between Ultragenyx Pharmaceutical Inc. and Kyowa Kirin Co., Ltd.	10-K	2/16/2022	10.13
10.13*	Amendment No. 12 to Collaboration and License Agreement, effective as of September 29, 2022, between Ultragenyx Pharmaceutical Inc. and Kyowa Kirin Co., Ltd.	10-Q	11/3/2022	10.1
10.14*	Amendment No. 13 to Collaboration and License Agreement, effective as of May 16, 2023, between Ultragenyx Pharmaceutical Inc. and Kyowa Kirin Co., Ltd.	10-Q	8/3/2023	10.1
10.15*	Unit Purchase Agreement, dated as of July 15, 2022, by and among Ultragenyx Pharmaceutical Inc., GeneTx Biotherapeutics LLC, the Unitholders and Deborah A. Guagliardo	10-Q	7/29/2022	10.2
10.16*	Commercial Supply and Services Agreement – Drug Substance, effective December 7, 2017, between Ultragenyx Europe GmbH and Rentschler Biopharma SE	10-K	2/21/2018	10.18
10.17*	Commercial Master Service Agreement – Drug Product, effective February 22, 2021, between Ultragenyx Pharmaceutical Inc. and BSP Pharmaceuticals S.p.A	10-K	2/17/2023	10.25
10.18*	Commercial Supply Agreement, dated June 19, 2023, between Ultragenyx Pharmaceutical Inc. and IOI Oleo GmbH				X
10.19*	Royalty Purchase Agreement, dated as of December 17, 2019, between Ultragenyx Pharmaceutical Inc. and RPI Finance Trust	10-K	2/14/2020	10.25
10.20*	Royalty Purchase Agreement, dated as of July 14, 2022, by and among Rare Delaware Inc., Ultragenyx Pharmaceutical Inc. and OCM LS23 Holdings LP	10-Q	7/29/2022	10.1
10.21#	2014 Incentive Plan (as amended)	10-K	2/17/2017	10.20
10.22#	Form of Incentive Stock Option Agreement (2014 Plan)	S-1/A	1/17/2014	10.14
10.23#	Form of Non Statutory Stock Option Agreement (Employees) (2014 Plan)	S-1/A	1/17/2014	10.15
10.24#	Form of Restricted Stock Unit Agreement (Employees) (2014 Plan)	10-Q	5/10/2016	10.1

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10.25#	Form of Non-Statutory Stock Option Agreement (Annual Grant for Directors) (2014 Plan)	10-Q	8/3/2021	10.2
10.26#	Form of Restricted Stock Unit Agreement (Annual Grant for Directors) (2014 Plan)	10-Q	8/3/2021	10.3
10.27#	Form of Non-Statutory Stock Option Agreement (Grant for New Directors) (2014 Plan)	10-Q	8/3/2021	10.4
10.28#	Form of Restricted Stock Unit Agreement (Grant for New Directors) (2014 Plan)	10-Q	8/3/2021	10.5
10.29#	2023 Incentive Plan	S-8	6/8/2023	4.4
10.30#	Form of Incentive Stock Option Agreement (2023 Plan)				X
10.31#	Form of Non Statutory Stock Option Agreement (Employees)(2023 Plan)				X
10.32#	Form of Restricted Stock Unit Agreement (Employees)(2023 Plan)				X
10.33#	Form of Non-Statutory Stock Option Agreement (Annual Grant for Directors) (2023 Plan)				X
10.34#	Form of Restricted Stock Unit Agreement (Annual Grant for Directors) (2023 Plan)				X
10.35#	Form of Non-Statutory Stock Option Agreement (Grant for New Directors)(2023 Plan)				X
10.36#	Form of Restricted Stock Unit Agreement (Grant for New Directors) (2023 Plan)				X
10.37#	Form of Performance Stock Unit Agreement (2022)	10-Q	5/6/2022	10.1
10.38#	Form of Performance Stock Unit Agreement (2023)	10-Q	5/4/2023	10.1
10.39#	Amended and Restated 2014 Employee Stock Purchase Plan	S-8	6/8/2023	4.5
10.40#	Corporate Bonus Plan	S-1/A	1/17/2014	10.27
10.41#	Employment Inducement Plan	10-K	2/12/2021	10.43
10.42#	First Amendment to Employment Inducement Plan	S-8	6/8/2023	4.7
10.43#	Form of Non Statutory Stock Option Agreement (Inducement Plan)	10-K	2/12/2021	10.44
10.44#	Form of Non Statutory Stock Option Agreement (Inducement Plan) (ex-US)	10-K	2/12/2021	10.45
10.45#	Form of Restricted Stock Unit Agreement (Inducement Plan)	10-K	2/12/2021	10.46
10.46#	Form of Restricted Stock Unit Agreement (Inducement Plan)(ex-US)	10-K	2/12/2021	10.47
10.47#	Ultragenyx Pharmaceutical Inc. Deferred Compensation Plan	10-Q	8/3/2021	10.1
10.48#	Amendment No. 1 to the Ultragenyx Pharmaceutical Inc. Deferred Compensation Plan	10-Q	11/3/2021	10.1
10.49#	Executive Employment Agreement, dated as of June 15, 2011, between Ultragenyx Pharmaceutical Inc. and Emil D. Kakkis, M.D., Ph.D.	S-1	11/8/2013	10.18
10.50#	Amendment No. 1 to Executive Employment Agreement, dated August 8, 2014, between Ultragenyx Pharmaceutical Inc. and Emil D. Kakkis, M.D., Ph.D.	10-Q	8/11/2014	10.2

85

10.51#	Amendment No. 2, dated September 13, 2022, to Executive Employment Agreement between Ultragenyx Pharmaceutical Inc. and Emil D. Kakkis, M.D., Ph.D.	10-Q	11/3/2022	10.2
10.52#	Offer Letter, dated as of October 31, 2011, between Ultragenyx Pharmaceutical Inc. and Thomas Kassberg	S-1	11/8/2013	10.19
10.53#	Amendment No. 1 to Offer Letter, dated as of August 8, 2014, between Ultragenyx Pharmaceutical Inc. and Thomas Kassberg	10-Q	8/11/2014	10.3
10.54#	Amendment No. 2, dated September 13, 2022, to Offer Letter between Ultragenyx Pharmaceutical Inc. and Thomas Kassberg	10-Q	11/3/2022	10.5
10.55#	Offer Letter, dated as of April 26, 2016, between Ultragenyx Pharmaceutical Inc. and Karah Parschauer	10-Q	8/9/2016	10.3
10.56#	Amendment, dated September 13, 2022, to Offer Letter between Ultragenyx Pharmaceutical Inc. and Karah Parschauer	10-Q	11/3/2022	10.6
10.57#	Offer Letter, dated as of February 20, 2015, between Ultragenyx Pharmaceutical Inc. and Dennis Huang	10-K	2/17/2017	10.36
10.58#	Amendment, dated September 13, 2022, to Offer Letter between Ultragenyx Pharmaceutical Inc. and Dennis Huang	10-Q	11/3/2022	10.7
10.59#	Offer Letter, dated as of June 11, 2015, between Ultragenyx Pharmaceutical Inc. and John R. Pinion II	10-K	2/17/2017	10.37
10.60#	Amendment, dated September 13, 2022, to Offer Letter between Ultragenyx Pharmaceutical Inc. and John R. Pinion II	10-Q	11/3/2022	10.9
10.61#	Amended and Restated Offer Letter, dated March 31, 2023, between Ultragenyx Pharmaceutical Inc. and Eric Crombez, M.D.	10-Q	5/4/2023	10.2
10.62#	Offer Letter, dated June 2, 2023, between Ultragenyx Pharmaceutical Inc. and Howard Horn	8-K	7/12/2023	10.1
10.63#	Amendment, dated September 6, 2023, to the Offer Letter between Ultragenyx Pharmaceutical Inc. and Howard Horn	8-K	9/8/2023	10.1
10.64#	Offer Letter, dated May 16, 2017, between Ultragenyx Pharmaceutical Inc. and Erik Harris	10-Q	8/2/2019	10.4
10.65#	Addendum #1, dated August 8, 2017, to Offer Letter dated May 16, 2017 between Ultragenyx Pharmaceutical Inc. and Erik Harris	10-Q	8/2/2019	10.5
10.66#	Addendum #2, dated June 19, 2019, to Offer Letter dated May 16, 2017 between Ultragenyx Pharmaceutical Inc. and Erik Harris	10-Q	8/2/2019	10.6
10.67#	Amendment No. 3, dated September 13, 2022, to Offer Letter between Ultragenyx Pharmaceutical Inc. and Erik Harris	10-Q	11/3/2022	10.8
10.68#	Form of Indemnification Agreement	10-K	3/24/2014	10.23
10.69	Standard Lease, dated as of July 5, 2011, between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc.	S-1	11/8/2013	10.22

86

10.70	Addendum One to Standard Lease, dated as of July 5, 2011, between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc.	10-K	2/26/2016	10.34
10.71	Addendum Two to Standard Lease, dated as of March 7, 2012, between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc.	10-K	2/26/2016	10.35
10.72	Addendum #3 to Standard Lease, effective as of February 12, 2014, between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc.	8-K	2/25/2014	10.1
10.73	Addendum #4 to Standard Lease, effective as of March 9, 2015, between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc.	8-K	3/13/2015	10.1
10.74	Addendum #5 to Standard Lease, effective as of April 7, 2015, between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc.	10-K	2/26/2016	10.38
10.75	Addendum #6 to Standard Lease, effective as of April 29, 2019, between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc.	10-Q	8/2/2019	10.3
10.76	Lease Agreement, dated as of December 8, 2015, between Marina Boulevard Property, LLC and Ultragenyx Pharmaceutical Inc.	10-K	2/26/2016	10.43
10.77	Lease Agreement, dated November 2, 2015, between Dimension Therapeutics, Inc. and ARE-MA Region No. 20, LLC, and Consent to Assignment to Ultragenyx Pharmaceutical Inc.	10-K	2/21/2018	10.66
10.78	First Amendment to Lease Agreement, dated March 20, 2018, between Ultragenyx Pharmaceutical Inc. and ARE-MA Region No. 20, LLC	10-Q	5/8/2018	10.6
10.79	Second Amendment to Lease Agreement, dated July 1, 2018, between Ultragenyx Pharmaceutical Inc. and ARE-MA Region No. 20, LLC	10-Q	8/3/2018	10.3
10.80	Third Amendment to the Lease Agreement, dated July 29, 2019, between Ultragenyx Pharmaceutical Inc. and ARE-MA Region No., LLC.	10-Q	7/30/2020	10.2
10.81	Amended and Restated Fourth Amendment, dated August 4, 2020, to the Lease Agreement between Ultragenyx Pharmaceutical Inc. and ARE-MA Region No., LLC.	10-Q	10/27/2020	10.5
10.82	Lease Agreement, dated December 15, 2019, between Ultragenyx Pharmaceutical Inc. and ARE-San Francisco No. 17, LLC.	10-K	2/12/2021	10.81
10.83	First Amendment, dated September 20, 2020, to the Lease Agreement between Ultragenyx Pharmaceutical Inc. and ARE-San Francisco No. 17, LLC.	10-K	2/12/2021	10.82
10.84	Second Amendment, dated October 21, 2020, to the Lease Agreement between Ultragenyx Pharmaceutical Inc. and ARE-San Francisco No. 17, LLC.	10-K	2/12/2021	10.83
10.85	Third Amendment, dated July 27, 2022, to the Lease Agreement between Ultragenyx Pharmaceutical Inc. and ARE-San Francisco No. 17, LLC	10-K	2/16/2023	10.92

87

10.86	Office Lease, dated April 19, 2019, between Ultragenyx Pharmaceutical Inc. and Woburn MCB II, LLC	10-K	2/14/2020	10.70
10.87	Commercial Lease, dated July 2, 2018, between Ultragenyx Pharmaceutical Inc. and 32 Leveroni LLC	10-K	2/14/2020	10.71
10.88	Lease, dated August 18, 2022, between Ultragenyx Pharmaceutical Inc. and Brickbottom I QOZB L.P.	10-K	2/17/2023	10.95
21.1	Subsidiaries of Ultragenyx Pharmaceutical Inc.				X
23.1	Consent of Independent Registered Public Accounting Firm				X
24.1	Power of Attorney (included on the signature page of this report)
31.1	Certification of Principal Executive Officer of Ultragenyx Pharmaceutical Inc., as required by Rule 13a-14(a) or Rule 15d-14(a) of the Exchange Act as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002				X
31.2	Certification of Principal Financial Officer of Ultragenyx Pharmaceutical Inc., as required by Rule 13a-14(a) or Rule 15d-14(a) of the Exchange Act as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002				X
32.1§	Certification by the Principal Executive Officer and Principal Financial Officer, as required by Rule 13a-14(b) or Rule 15d-14(b) and Section 1350 of Chapter 36 of Title 18 of the United States Code (18 U.S.C. §1350)				X
97.1	Ultragenyx Pharmaceutical Inc. Clawback Policy				X
101.INS	XBRL Instance Document, formatted in Inline XBRL				X
101.SCH	Inline XBRL Taxonomy Extension Schema Document				X
104	The cover page from this Annual Report on Form 10-K, formatted in Inline XBRL and contained in Exhibit 101				X

* Certain identified information has been omitted by means of marking such information with asterisks in reliance on Item 601(b)(10)(iv) of Regulation S-K because it is both (i) not material and (ii) the type that the registrant treats as private or confidential.

# Indicates management contract or compensatory plan.

§ The certification attached as Exhibit 32.1 that accompanies this Annual Report is not deemed filed with the SEC and is not to be incorporated by reference into any filing of Ultragenyx Pharmaceutical Inc. under the Securities Act or the Exchange Act, whether made before or after the date of this Annual Report, irrespective of any general incorporation language contained in such filing.

Item 16. Form 10-K Summary

None.

88

SIGNATURES

Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

ULTRAGENYX PHARMACEUTICAL Inc.
By:	/s/ Emil D. Kakkis
	Emil D. Kakkis, M.D., Ph.D.
	President and Chief Executive Officer (Principal Executive Officer)

Date: February 21, 2024

POWER OF ATTORNEY

KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Emil D. Kakkis, M.D., Ph.D. and Howard Horn, and each of them, as his or her true and lawful attorneys-in-fact and agents, with full power of substitution for him or her, and in his or her name in any and all capacities, to sign any and all amendments to this Annual Report, and to file the same, with exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact and agents, and each of them, full power and authority to do and perform each and every act and thing requisite and necessary to be done therewith, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming all that said attorneys-in-fact and agents, and any of them, his or her substitute or substitutes, may lawfully do or cause to be done by virtue hereof.

Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of the registrant and in the capacities and on the dates indicated.

	Signature		Title		Date
/s/ Emil D. Kakkis  Emil D. Kakkis, M.D., Ph.D.		President and Chief Executive Officer and Director (Principal Executive Officer)		February 21, 2024
/s/ Howard Horn  Howard Horn		Executive Vice President, Chief Financial Officer, Corporate Strategy (Principal Financial Officer)		February 21, 2024
/s/ Theodore A. Huizenga  Theodore A. Huizenga		Senior Vice President and Chief Accounting Officer (Principal Accounting Officer)		February 21, 2024
/s/ Daniel G. Welch  Daniel G. Welch		Chairman of the Board		February 21, 2024
/s/ Deborah Dunsire Deborah Dunsire, M.D.		Director		February 21, 2024
/s/ Matthew K. Fust  Matthew K. Fust		Director		February 21, 2024
/s/ Michael Narachi  Michael Narachi		Director		February 21, 2024
/s/ Amrit Ray		Director		February 21, 2024
Amrit Ray, M.D.
/s/ Corsee D. Sanders		Director		February 21, 2024
Corsee D. Sanders, Ph.D.
/s/ Shehnaaz Suliman		Director		February 21, 2024
Shehnaaz Suliman, M.D.

89

Ultragenyx Pharmaceutical Inc.

INDEX TO FINANCIAL STATEMENTS

	Page
Report of Independent Registered Public Accounting Firm (PCAOB ID: 42)	F-2
Consolidated Financial Statements:
Consolidated Balance Sheets	F-4
Consolidated Statements of Operations	F-5
Consolidated Statements of Comprehensive Loss	F-5
Consolidated Statements of Stockholders’ Equity	F-6
Consolidated Statements of Cash Flows	F-7
Notes to Consolidated Financial Statements	F-9

F-1

Report of Independent Registered Public Accounting Firm

To the Stockholders and the Board of Directors of Ultragenyx Pharmaceutical Inc.

Opinion on the Financial Statements

We have audited the accompanying consolidated balance sheets of Ultragenyx Pharmaceutical Inc. (the Company) as of December 31, 2023 and 2022, the related consolidated statements of operations, comprehensive loss, stockholders' equity and cash flows for each of the three years in the period ended December 31, 2023, and the related notes (collectively referred to as the “consolidated financial statements”). In our opinion, the consolidated financial statements present fairly, in all material respects, the financial position of the Company at December 31, 2023 and 2022, and the results of its operations and its cash flows for each of the three years in the period ended December 31, 2023, in conformity with U.S. generally accepted accounting principles.

We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the Company's internal control over financial reporting as of December 31, 2023, based on criteria established in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework), and our report dated February 21, 2024 expressed an unqualified opinion thereon.

Basis for Opinion

These financial statements are the responsibility of the Company's management. Our responsibility is to express an opinion on the Company’s financial statements based on our audits. We are a public accounting firm registered with the PCAOB and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.

Critical Audit Matter

The critical audit matter communicated below is a matter arising from the current period audit of the financial statements that was communicated or required to be communicated to the audit committee and that: (1) relates to accounts or disclosures that are material to the financial statements and (2) involved our especially challenging, subjective or complex judgments. The communication of the critical audit matter does not alter in any way our opinion on the consolidated financial statements, taken as a whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the critical audit matter or on the accounts or disclosures to which it relates.

Liabilities for sales of future royalties

Description of the Matter

As discussed in Note 10, the Company has entered into two royalty purchase agreements, under which the Company sold its rights to receive royalty payments arising from the net sales of Crysvita in the European and North American markets in exchange for $320 million and $500 million, respectively. The proceeds from each transaction were recorded as liabilities that are being amortized using the effective interest method over the estimated lives of the respective arrangements. In order to determine the amortization of the liabilities, the Company is required to estimate the total amount of future royalty payments to be paid to the respective counterparty, subject to the capped amount, over the life of the arrangement. The Company estimates an imputed interest on the unamortized portion of the liability and records non-cash interest expense relating to the transaction. Auditing the Company’s liabilities related to the sale of future royalties was complex due to the subjective judgments required to forecast the expected royalty payments subject to each agreement. Specifically, the forecasted revenues of Crysvita involve significant estimation uncertainty given the limited historical Crysvita sales data.

F-2

How We Addressed the Matter in Our Audit We obtained an understanding, evaluated the design and tested the operating effectiveness of controls over the Company’s process of accounting for the liabilities related to the sale of future royalties, including controls over the Company’s estimates of projected sales of Crysvita in the European and North American markets.   To test management’s estimates of the future royalties and the imputed effective interest rates, we performed audit procedures that included, among others, evaluating the reasonableness of management’s assumptions related to the treatable patient populations, estimated pricing and reimbursement, and the rate of adoption. We compared the significant assumptions with historical trends of actual sales, analyst expectations and performed sensitivity analyses of estimated future royalties to evaluate the changes in the future royalties on the implied effective interest rates.

/s/ Ernst & Young LLP

We have served as the Company’s auditor since 2012.

San Mateo, California

February 21, 2024

F-3

ULTRAGENYX PHARMACEUTICAL INC.

CONSOLIDATED BALANCE SHEETS

(In thousands, except share and per share amounts)

	December 31,
	2023			2022
ASSETS
Current assets:
Cash and cash equivalents	$	213,584		$	132,944
Marketable debt securities		363,625			614,818
Accounts receivable, net		73,390			40,445
Inventory		33,969			26,766
Other assets		47,616			68,926
Total current assets		732,184			883,899
Property, plant, and equipment, net		290,566			259,726
Marketable debt securities		199,901			148,970
Intangible assets, net		166,271			160,105
Goodwill		44,406			44,406
Other assets		57,685			48,338
Total assets	$	1,491,013		$	1,545,444
LIABILITIES AND STOCKHOLDERS' EQUITY
Current liabilities:
Accounts payable	$	42,114		$	43,274
Accrued liabilities		196,486			204,678
Contract liabilities		—			1,479
Lease liabilities		12,595			11,779
Liabilities for sales of future royalties		29,242			—
Total current liabilities		280,437			261,210
Lease liabilities		30,574			19,814
Deferred tax liabilities		30,058			31,667
Liabilities for sales of future royalties		862,325			875,439
Other liabilities		12,205			4,820
Total liabilities		1,215,599			1,192,950
Commitments and contingencies (Notes 9 and 15)
Stockholders’ equity:
Preferred stock, par value of $0.001 per share—25,000,000 shares authorized; nil    outstanding in 2023 and in 2022		—			—
Common stock, par value of $0.001 per share—250,000,000 shares authorized;   outstanding—82,315,590 in 2023 and 70,197,297 in 2022		82			70
Treasury stock, at cost, 9,559 in 2023 and nil in 2022		(432	)		—
Deferred compensation obligation		432			—
Additional paid-in capital		3,662,346			3,140,019
Accumulated other comprehensive income (loss)		647			(6,573	)
Accumulated deficit		(3,387,661	)		(2,781,022	)
Total stockholders’ equity		275,414			352,494
Total liabilities and stockholders’ equity	$	1,491,013		$	1,545,444

See accompanying notes.

F-4

ULTRAGENYX PHARMACEUTICAL INC.

CONSOLIDATED STATEMENTS OF OPERATIONS

(In thousands, except share and per share amounts)

	Year Ended December 31,
	2023			2022			2021
Revenues:
Product sales	$	180,413		$	118,927		$	77,017
Royalty revenue		182,652			21,692			17,951
Collaboration and license		71,184			222,710			256,438
Total revenues		434,249			363,329			351,406
Operating expenses:
Cost of sales		45,209			28,320			16,008
Research and development		648,449			705,789			497,153
Selling, general and administrative		309,799			278,139			219,982
Total operating expenses		1,003,457			1,012,248			733,143
Loss from operations		(569,208	)		(648,919	)		(381,737	)
Interest income		26,688			11,074			1,928
Change in fair value of equity investments		397			(19,299	)		(42,063	)
Non-cash interest expense on liabilities for sales of future royalties		(66,004	)		(43,015	)		(29,422	)
Other expense		(337	)		(1,566	)		(1,687	)
Loss before income taxes		(608,464	)		(701,725	)		(452,981	)
Benefit from (provision for) income taxes		1,825			(5,696	)		(1,044	)
Net loss	$	(606,639	)	$	(707,421	)	$	(454,025	)
Net loss per share, basic and diluted	$	(8.25	)	$	(10.12	)	$	(6.70	)
Shares used in computing net loss per share, basic and diluted		73,543,862			69,914,225			67,795,540

See accompanying notes.

ULTRAGENYX PHARMACEUTICAL INC.

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS

(In thousands)

	Year Ended December 31,
	2023			2022			2021
Net loss	$	(606,639	)	$	(707,421	)	$	(454,025	)
Other comprehensive income (loss):
Foreign currency translation adjustments		239			(724	)		(550	)
Unrealized gain (loss) on available-for-sale securities		6,981			(4,445	)		(1,543	)
Other comprehensive income (loss):		7,220			(5,169	)		(2,093	)
Total comprehensive loss	$	(599,419	)	$	(712,590	)	$	(456,118	)

See accompanying notes.

F-5

ULTRAGENYX PHARMACEUTICAL INC.

CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY

(In thousands, except share amounts)

	Common Stock				Additional Paid-In		Accumulated Other Comprehensive			Accumulated			Treasury			Deferred Compensation		Total Stockholders'
	Shares		Amount		Capital		Income (Loss)			Deficit			Stock			Obligation		Equity
Balance as of December 31, 2020		66,818,520	$	67	$	2,773,195	$	689		$	(1,619,576	)	$	—		$	—	$	1,154,375
Issuance of common stock in connection with at-the-market     offering, net of issuance costs		1,050,372		1		78,942		—			—			—			—		78,943
Stock-based compensation		—		—		105,260		—			—			—			—		105,260
Issuance of common stock under    equity plan awards, net of tax		1,476,106		1		40,100		—			—			—			—		40,101
Other comprehensive loss		—		—		—		(2,093	)		—			—			—		(2,093	)
Net loss		—		—		—		—			(454,025	)		—			—		(454,025	)
Balance as of December 31, 2021		69,344,998	$	69	$	2,997,497	$	(1,404	)	$	(2,073,601	)	$	—		$	—	$	922,561
Stock-based compensation		—		—		131,710		—			—			—			—		131,710
Issuance of common stock under    equity plan awards, net of tax		852,299		1		10,812		—			—			—			—		10,813
Other comprehensive loss		—		—		—		(5,169	)		—			—			—		(5,169	)
Net loss		—		—		—		—			(707,421	)		—			—		(707,421	)
Balance as of December 31, 2022		70,197,297	$	70	$	3,140,019	$	(6,573	)	$	(2,781,022	)	$	—		$	—	$	352,494
Issuance of common stock and pre-funded warrants in connection with underwritten    public offering, net of issuance costs		9,833,334		10		326,446		—			—			—			—		326,456
Issuance of common stock in connection with   at-the-market offering, net of issuance costs		1,175,584		1		53,298		—			—			—			—		53,299
Stock-based compensation		—		—		134,169		—			—			—			—		134,169
Issuance of common stock under    equity plan awards, net of tax		1,109,375		1		8,414		—			—			—			—		8,415
Deferred compensation		—		—		—		—			—			(432	)		432		—
Other comprehensive income		—		—		—		7,220			—			—			—		7,220
Net loss		—		—		—		—			(606,639	)		—			—		(606,639	)
Balance as of December 31, 2023		82,315,590	$	82	$	3,662,346	$	647		$	(3,387,661	)	$	(432	)	$	432	$	275,414

See accompanying notes.

F-6

ULTRAGENYX PHARMACEUTICAL INC.

CONSOLIDATED STATEMENTS OF CASH FLOWS

(In thousands)

	Year Ended December 31,
	2023			2022			2021
Operating activities:
Net loss	$	(606,639	)	$	(707,421	)	$	(454,025	)
Adjustments to reconcile net loss to net cash used in operating activities:
Stock-based compensation		135,227			130,377			104,952
Acquired in-process research and development		—			75,033			—
Amortization of premium (discount) on marketable debt securities, net		(12,842	)		2,699			6,606
Depreciation and amortization		26,006			18,220			13,239
Change in fair value of equity investments		(397	)		19,299			42,063
Non-cash collaboration royalty revenue		(69,364	)		(21,692	)		(17,951	)
Non-cash interest expense on liabilities for sales of future royalties		66,004			43,015			29,422
Other		2,300			(230	)		235
Changes in operating assets and liabilities:
Accounts receivable		(22,778	)		(12,068	)		(5,432	)
Inventory		(6,930	)		(9,701	)		(3,117	)
Other assets		15,325			3,798			(29,508	)
Accounts payable, accrued, and other liabilities		2,380			87,442			32,313
Contract liabilities, net		(1,479	)		(7,597	)		(57,492	)
Deferred tax liabilities		(1,619	)		(1,639	)		—
Net cash used in operating activities		(474,806	)		(380,465	)		(338,695	)
Investing activities:
Purchase of property, plant, and equipment		(44,267	)		(116,123	)		(73,093	)
Acquisition, net of cash acquired		—			(75,025	)		—
Purchase of marketable debt securities		(526,382	)		(614,735	)		(1,012,187	)
Proceeds from sale of marketable debt securities		50,672			84,275			92,896
Proceeds from sale of equity investments		—			10,094			79,843
Proceeds from maturities of marketable debt securities		695,525			450,706			718,111
Payment for intangible asset		(2,500	)		(30,000	)		—
Other		(5,048	)		(844	)		(942	)
Net cash provided by (used in) investing activities		168,000			(291,652	)		(195,372	)
Financing activities:
Proceeds from the sale of future royalties, net		—			490,950			—
Proceeds from the issuance of common stock and pre-funded warrants in connection with underwritten     public offerings, net of issuance costs		326,456			—			—
Proceeds from the issuance of common stock in connection with at-the-market    offering, net of issuances costs		53,299			—			78,943
Proceeds from the issuance of common stock from exercise of warrants and equity     plan awards, net		8,415			10,813			40,101
Other		(28	)		(555	)		(492	)
Net cash provided by financing activities		388,142			501,208			118,552
Effect of exchange rate changes on cash		462			(1,075	)		(1,194	)
Net increase (decrease) in cash, cash equivalents, and restricted cash		81,798			(171,984	)		(416,709	)
Cash, cash equivalents, and restricted cash at beginning of year		137,601			309,585			726,294
Cash, cash equivalents, and restricted cash at end of year	$	219,399		$	137,601		$	309,585

F-7

See accompanying notes.

ULTRAGENYX PHARMACEUTICAL INC.

CONSOLIDATED STATEMENTS OF CASH FLOWS

(In thousands)

	Year Ended December 31,
	2023		2022		2021
Supplemental disclosures of non-cash investing and financing information:
Acquired lease liabilities arising from obtaining right-of-use assets and property, plant, and equipment	$	22,162	$	1,168	$	3,142
Costs of property, plant and equipment included in accounts payable, accrued, and other liabilities	$	1,577	$	17,963	$	18,993
Non-cash interest expense on liabilities for sales of future royalties capitalized during the year into ending property, plant and equipment	$	9,431	$	11,380	$	4,650

See accompanying notes.

F-8

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements

1.Organization and Basis of Presentation

Ultragenyx Pharmaceutical Inc., or the Company, is a biopharmaceutical company incorporated in Delaware.

The Company is focused on the identification, acquisition, development, and commercialization of novel products for the treatment of serious rare and ultrarare genetic diseases. The Company operates as one reportable segment and has four commercially approved products.

Crysvita® (burosumab) is approved in the United States, or U.S., the European Union, or EU, and certain other regions for the treatment of X-linked hypophosphatemia, or XLH, in adult and pediatric patients one year of age and older. Crysvita is also approved in the U.S. and certain other regions for the treatment of fibroblast growth factor 23, or FGF23-related hypophosphatemia in tumor-induced osteomalacia, or TIO, associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older.

Mepsevii® (vestronidase alfa) is approved in the U.S., the EU and certain other regions, as the first medicine for the treatment of children and adults with mucopolysaccharidosis VII, or MPS VII, also known as Sly syndrome.

Dojolvi® (triheptanoin) is approved in the U.S. and certain other regions for the treatment of pediatric and adult patients severely affected by long-chain fatty acid oxidation disorders, or LC-FAOD.

Evkeeza® (evinacumab) is approved in the U.S. and the European Economic Area, or EEA, for the treatment of homozygous familial hypercholesterolemia, or HoFH. The Company has exclusive rights to commercialize Evkeeza® (evinacumab) outside of the U.S.

In addition to the approved products, the Company has the following ongoing clinical development programs:

•UX111 (formerly ABO-102) is an AAV9 gene therapy product candidate for the treatment of patients with Sanfilippo syndrome type A, or MPS IIIA, a rare lysosomal storage disease;

•DTX401 is an adeno-associated virus 8, or AAV8, gene therapy product candidate for the treatment of patients with glycogen storage disease type Ia, or GSDIa;

•DTX301 is an AAV8 gene therapy product candidate in development for the treatment of patients with ornithine transcarbamylase, or OTC deficiency, the most common urea cycle disorder;

•UX143 (setrusumab), which is subject to the Company’s collaboration agreement with Mereo BioPharma 3, or Mereo, is a fully human monoclonal antibody that inhibits sclerostin, a protein that acts on a key bone-signaling pathway and inhibits the activity of bone-forming cells for the treatment of patients with osteogenesis imperfect, or OI;

•GTX-102 is an antisense oligonucleotide, or ASO for the treatment of Angelman syndrome, a debilitating and rare neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene.; and

•UX701 is an adeno-associated virus 9, or AAV9, gene therapy designed to deliver stable expression of a truncated version of the ATP7B copper transporter following a single intravenous infusion to improve copper distribution and excretion from the body and reverse pathological findings of Wilson liver disease;

The Company has sustained operating losses and expects such annual losses to continue over the next several years. The Company’s ultimate success depends on the outcome of its research and development and commercialization activities. Through December 31, 2023, the Company has relied primarily on its sale of equity securities, its revenues from commercial products, its sale of future royalties, and strategic collaboration arrangements to finance its operations. The Company may need to raise additional capital to fully implement its business plans through the issuance of equity, borrowings, or strategic alliances with partner companies. However, if such financing is not available at adequate levels, the Company would need to reevaluate its operating plans.

2.Summary of Significant Accounting Policies

Basis of Consolidation

The Consolidated Financial Statements include the accounts of Ultragenyx Pharmaceutical Inc. and its wholly owned subsidiaries. All intercompany balances and transactions have been eliminated.

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

Use of Estimates

The accompanying Consolidated Financial Statements have been prepared in accordance with U.S. generally accepted accounting principles, or GAAP. The preparation of the Consolidated Financial Statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, disclosure of contingent liabilities and the reported amounts of expenses in the Consolidated Financial Statements and the accompanying notes. On an ongoing basis, management evaluates its estimates, including those related to clinical trial accruals, fair value of assets and liabilities, income taxes, stock-based compensation, revenue recognition, and the liabilities for sales of future royalties. Management bases its estimates on historical experience and on various other market-specific and relevant assumptions that management believes to be reasonable under the circumstances. Actual results could differ from those estimates.

Cash, Cash Equivalents, and Restricted Cash

The Company considers all highly liquid investments with original maturities of three months or less from the date of purchase to be cash equivalents. Cash equivalents consist primarily of amounts invested in money market accounts.

Restricted cash primarily consists of money market accounts used as collateral for the Company’s obligations under its facility leases and the gene therapy building construction project.

The following table provides a reconciliation of cash, cash equivalents, and restricted cash reported within the Consolidated Balance Sheets that sum to the total of the same such amounts shown in the Consolidated Statements of Cash Flows (in thousands):

	December 31,
	2023		2022		2021
Cash and cash equivalents	$	213,584	$	132,944	$	307,584
Restricted cash included in other current assets		2,008		862		—
Restricted cash included in other non-current assets		3,807		3,795		2,001
Total cash, cash equivalents, and restricted cash     shown in the statements of cash flows	$	219,399	$	137,601	$	309,585

Marketable Debt Securities

All marketable debt securities have been classified as “available-for-sale” and are carried at estimated fair value as determined based upon quoted market prices or pricing models for similar securities. Management determines the appropriate classification of its investments at the time of purchase and reevaluates such designation as of each balance sheet date. Investments with a maturity of one year or less from the balance sheet date are reported as current marketable debt securities and investments with a maturity of greater than one year from the balance sheet date are reported as non-current marketable debt securities. Unrealized gains and losses are excluded from earnings and are reported as a component of comprehensive loss. Realized gains and losses and declines in fair value judged to be other than temporary, if any, on available-for-sale securities are included in other income (expense). The cost of securities sold is based on the specific-identification method. Interest on investments is included in interest income.

Equity Investments

The Company records investments in equity securities, other than equity method investments, at fair market value, if the fair value is readily determinable. Equity securities with no readily determinable fair values are recorded using the measurement alternative of cost adjusted for observable price changes in orderly transactions for identical or similar investments of the same issuer less impairment, if any. Investments in equity securities are recorded in Equity investments on the Company's Consolidated Balance Sheets. Unrealized gains and losses are reported in Change in fair value of equity investments on the Company’s Consolidated Statements of Operations. The Company regularly reviews its non-marketable equity securities for indicators of impairment.

F-10

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

Concentration of Credit Risk, Credit Losses, and Other Risks and Uncertainties

Financial instruments that potentially subject the Company to a concentration of credit risk consist of cash, cash equivalents, and investments. The Company’s cash, cash equivalents, and investments are held by financial institutions that management believes are of high credit quality. The Company’s investment policy limits investments to fixed income securities denominated and payable in U.S. dollars such as U.S. government obligations, money market instruments and funds, corporate bonds, commercial paper, and asset-backed securities and places restrictions on maturities and concentrations by type and issuer. Such deposits may, at times, exceed federally insured limits. The Company has not experienced any losses on its deposits of cash and cash equivalents and its accounts are monitored by management to mitigate risk. The Company is exposed to credit risk in the event of default by the financial institutions holding its cash and cash equivalents, corporate issuers, and other financial instruments, to the extent recorded in the Consolidated Balance Sheets.

The Company is exposed to credit losses primarily through receivables from customers and collaborators and through its available-for-sale debt securities. For trade receivables and other instruments, the Company uses a forward-looking expected loss model that generally results in the earlier recognition of allowances for losses. For available-for-sale debt securities with unrealized losses, the losses are recognized as allowances rather than as reductions in the amortized cost of the securities.

The Company’s expected loss allowance methodology for the receivables is developed using historical collection experience, current and future economic market conditions, a review of the current aging status and financial condition of the entities. Specific allowance amounts are established to record the appropriate allowance for customers that have a higher probability of default. Balances are written off when determined to be uncollectible. The Company’s expected loss allowance methodology for the debt securities is developed by reviewing the extent of the unrealized loss, the size, term, geographical location, and industry of the issuer, the issuers’ credit ratings and any changes in those ratings, as well as reviewing current and future economic market conditions and the issuers’ current status and financial condition. There was no allowance for losses on available-for-sale debt securities which were attributable to credit risk for the years ended December 31, 2023 and 2022.

The Company is dependent on third-party manufacturers to supply products for research and development activities in its programs. In particular, the Company relies and expects to continue to rely on a small number of manufacturers to supply it with its requirements for the active pharmaceutical ingredients and formulated drugs related to these programs. These programs could be adversely affected by a significant interruption in the supply of active pharmaceutical ingredients and formulated drugs.

Inventory

The Company values inventory at the lower of cost and net realizable value and determines the cost of inventory using the average-cost method. The Company expenses costs associated with the manufacture of product candidates prior to regulatory approval. Inventories consist of currently approved products. The Company periodically reviews its inventories for excess amounts or obsolescence and writes down obsolete or otherwise unmarketable inventory to its estimated net realizable value. Management determines excess inventory based on expected future demand. Estimates related to future demand are sensitive to significant inputs and assumptions such as acceptance by patients and physicians and the availability of formulary coverage and adequate reimbursement from private third-party payers for the product.

Property, Plant, and Equipment

Property, plant, and equipment are stated at cost, less accumulated depreciation and amortization. Depreciation and amortization is computed using the straight-line method over the estimated useful lives of the respective assets. Depreciation and amortization begins when the asset is placed in service. Interest costs incurred during the construction of major capital projects are capitalized until the underlying asset is ready to be placed in service. Maintenance and repairs are charged to operations as incurred. Upon sale or retirement of assets, the cost and related accumulated depreciation or amortization are removed from the balance sheet and the resulting gain or loss, if any, is reflected in operations. See “Note 4. Balance Sheet Components” for further disclosure on the useful lives of property, plant, and equipment.

Intangible Assets

Finite-lived intangibles consist of contractual payments made for certain milestones achieved with collaboration partners. The contractual payments are recorded as intangible assets and are amortized over their estimated useful lives. The Company reviews its definite-lived intangible assets when events or circumstances may indicate that the carrying value of these assets is not recoverable and exceeds their fair value. The Company measures fair value based on the estimated future undiscounted cash flows associated with these assets in addition to other assumptions and projections that the Company deems to be reasonable and supportable.

F-11

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

Indefinite-lived intangibles consist of acquired in-process research and development, or IPR&D. IPR&D assets represent capitalized incomplete research projects that the Company acquired through business combinations. Such assets are initially measured at their acquisition date fair values and are tested for impairment annually and whenever events or changes in circumstances indicate that the carrying amount may not be recoverable. When development of the project is complete, which generally occurs when regulatory approval to market a product is obtained, the associated assets will be deemed finite-lived and will be amortized over a period that best reflects the economic benefits provided by these assets.

If it is determined that an intangible asset becomes impaired, the carrying value is written down to its fair value with the related impairment charge recognized in Consolidated Statements of Operations in the period in which the impairment occurs. The Company has not recorded any impairments of intangible assets to date.

Goodwill

Goodwill represents the excess of purchase price over fair value of net assets acquired in a business combination and is not amortized. Goodwill is subject to impairment testing at least annually during the fourth quarter or when a triggering event occurs that could indicate a potential impairment. If it is determined that the goodwill becomes impaired, the carrying value is written down to its fair value with the related impairment charge recognized in Consolidated Statements of Operations in the period in which the impairment occurs. The Company has not recorded any impairments of goodwill.

Impairment of Long-Lived Assets

The Company evaluates its long-lived assets, including property and equipment, for impairment whenever events or changes in circumstances indicate that the carrying value of these assets may not be recoverable. Recoverability of these assets is measured by comparison of the carrying amount of each asset to the future undiscounted cash flows expected to result from the use of the asset and its eventual disposition. If the asset is considered to be impaired, the amount of any impairment is measured as the difference between the carrying value and the fair value of the impaired asset. The Company has not recorded material impairment of any long-lived assets.

Accruals of Research and Development Costs

The Company records accruals for estimated costs of research, preclinical and clinical studies and manufacturing development. These costs are a significant component of the Company’s research and development expenses. A substantial portion of the Company’s ongoing research and development activities are conducted by third-party service providers, including contract research organizations. The Company accrues the costs incurred under its agreements with these third parties based on actual work completed in accordance with agreements established with these third parties. The Company determines the actual costs through obtaining information from external service providers as to the progress or stage of completion of the services and the agreed-upon fee to be paid for such services.

Revenue Recognition

Product Sales

The Company sells its approved products through a limited number of distributors. Under ASC 606, revenue from product sales is recognized at the point in time when control is transferred to these distributors. The Company also recognizes revenue from sales of certain products on a “named patient” basis, which are allowed in certain countries prior to the commercial approval of the product. Prior to recognizing revenue, the Company makes estimates of the transaction price, including any variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Product sales are recorded net of estimated government-mandated rebates and chargebacks, estimated product returns, and other deductions.

Provisions for returns and other adjustments are provided for in the period the related revenue is recorded, as estimated by management. These reserves are based on estimates of the amounts earned or to be claimed on the related sales and are reviewed periodically and adjusted as necessary. The Company’s estimates of government mandated rebates, chargebacks, estimated product returns, and other deductions depends on the identification of key customer contract terms and conditions, as well as estimates of sales volumes to different classes of payors. If actual results vary, the Company may need to adjust these estimates, which could have a material effect on earnings in the period of the adjustment.

F-12

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

Collaboration, License, and Royalty Revenue

The Company has certain license and collaboration agreements that are within the scope of Accounting Standards Codification, or ASC, 808, Collaborative Agreements, which provides guidance on the presentation and disclosure of collaborative arrangements. Generally, the classification of the transactions under the collaborative arrangements is determined based on the nature of contractual terms of the arrangement, along with the nature of the operations of the participants. The Company records its share of collaboration revenue, net of transfer pricing related to net sales in the period in which such sales occur, if the Company is considered as an agent in the arrangement. The Company is considered an agent when the collaboration partner controls the product before transfer to the customers and has the ability to direct the use of and obtain substantially all of the remaining benefits from the product. Funding received related to research and development services and commercialization costs is generally classified as a reduction of research and development expenses and selling, general and administrative expenses, respectively, in the Consolidated Statements of Operations, because the provision of such services for collaborative partners are not considered to be part of the Company’s ongoing major or central operations.

The Company utilizes certain information from its collaboration partners to record collaboration revenue, including revenue from the sale of the product, associated reserves on revenue, and costs incurred for development and sales activities. For the periods covered in the financial statements presented, there have been no material changes to prior period estimates of revenues and expenses. The Company also records royalty revenues under certain of the Company’s license or collaboration agreements in exchange for license of intellectual property.

The Company sold the right to receive certain royalty payments from net sales of Crysvita in certain territories to RPI Finance Trust, or RPI, an affiliate of Royalty Pharma, and to OCM LS23 Holdings LP, an investment vehicle for Ontario Municipal Employees Retirement System, or OMERS, as further described in “Note 10. Liabilities for Sales of Future Royalties.” The Company records the royalty revenue from the net sales of Crysvita in the applicable territories on a prospective basis as non-cash royalty revenue in the Consolidated Statements of Operations over the term of the applicable arrangement.

The terms of the Company’s collaboration and license agreements may contain multiple performance obligations, which may include licenses and research and development activities. The Company evaluates these agreements under ASC 606, Revenue from Contracts with Customers, or ASC 606, to determine the distinct performance obligations. The Company analogizes to ASC 606 for the accounting for distinct performance obligations for which there is a customer relationship. Prior to recognizing revenue, the Company makes estimates of the transaction price, including variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Total consideration may include nonrefundable upfront license fees, payments for research and development activities, reimbursement of certain third-party costs, payments based upon the achievement of specified milestones, and royalty payments based on product sales derived from the collaboration.

If there are multiple distinct performance obligations, the Company allocates the transaction price to each distinct performance obligation based on its relative standalone selling price. The standalone selling price is generally determined based on the prices charged to customers or using expected cost-plus margin. The Company estimates the efforts needed to complete the performance obligations and recognizes revenue by measuring the progress towards complete satisfaction of the performance obligations using input measures.

Deferred Compensation Plan

The Company maintains a nonqualified deferred compensation plan whereby certain employees and members of the board of directors are able to defer certain equity awards and other compensation. Amounts deferred are invested into shares of the Company's common stock, mutual funds, and other investment options. The plan complies with the provisions of Section 409A of the Internal Revenue Code. All of the various mutual funds held in the plan are classified as trading securities and recorded at fair value in other non-current assets in the Consolidated Balance Sheets with changes in fair value recognized as earnings in the period they occur. The short-term portion of the corresponding liability for the plan is included in accrued expenses. The long-term portion of the liability is included in other non-current liabilities in the Consolidated Balance Sheets. Certain equity awards deferred under the plan are required to be settled through the issuance of Company stock. These awards are recorded as treasury stock and deferred compensation obligation within stockholders’ equity.

Leases

Lease agreements are evaluated to determine whether an arrangement is or contains a lease in accordance with ASC 842, Leases. The Company determines if an arrangement includes a lease at inception. Right-of-use lease assets and lease liabilities are

F-13

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

recognized based on the present value of the future minimum lease payments over the lease term at the commencement date. The right-of-use lease asset includes any lease payments made and excludes lease incentives. Incremental borrowing rate is used in determining the present value of future payments. The Company applies a portfolio approach to the property leases to apply an incremental borrowing rate to leases with similar lease terms. The lease terms may include options to extend or terminate the lease. The Company recognizes the options to extend the lease as part of the right-of-use lease assets and lease liabilities only if it is reasonably certain that the option would be exercised. Lease expense for minimum lease payments is recognized on a straight-line basis over the non-cancelable lease term. The Company has elected to not separate lease and non-lease components. See “Note 9. Leases” for further disclosure.

Comprehensive Loss

Comprehensive loss is the change in stockholders’ equity from transactions and other events and circumstances other than those resulting from investments by stockholders and distributions to stockholders. The Company’s other comprehensive loss is comprised of unrealized gains and losses on investments in available-for-sale securities and foreign currency translation adjustments.

Research and Development

Research and development costs are expensed as incurred and consist of salaries and benefits, stock-based compensation expense, lab supplies and facility costs, as well as fees paid to other nonemployees and entities that conduct certain research and development activities on the Company’s behalf. Amounts incurred in connection with license agreements are also included in research and development expense. Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are deferred. The deferred amounts are expensed as the related goods are delivered or the services are performed.

Stock-Based Compensation

Stock-based awards issued to employees, including stock options, performance stock options, or PSOs, restricted stock units, or RSUs, and performance stock units, or PSUs are recorded at fair value as of the grant date and recognized as expense on a straight-line basis over the employee’s requisite service period (generally the vesting period). PSOs and PSUs vest only if certain specified criteria are achieved and the employees’ continued service requirements are met; therefore, the expense recognition occurs when the likelihood of the PSOs and PSUs being earned is deemed probable. Stock compensation expense on awards expected to vest is recognized net of estimated forfeitures.

Income Taxes

The Company uses the liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are determined based on the differences between the financial reporting and the tax bases of assets and liabilities and are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. The Company must then assess the likelihood that the resulting deferred tax assets will be realized. A valuation allowance is provided when it is more likely than not that some portion or all of a deferred tax asset will not be realized. Due to the Company’s lack of earnings history, the net deferred tax assets have been fully offset by a valuation allowance.

In conjunction with the acquisition of Dimension Therapeutics, Inc., or Dimension, a deferred tax liability was recorded reflecting the tax impact of the difference between the book basis and tax basis of acquired IPR&D. Such deferred income tax liability is not used to offset deferred tax assets when analyzing the Company’s valuation allowance as the acquired IPR&D is considered to have an indefinite life until the Company completes or abandons development of the acquired IPR&D.

The Company recognizes benefits of uncertain tax positions if it is more likely than not that such positions will be sustained upon examination based solely on their technical merits, as the largest amount of benefit that is more likely than not to be realized upon the ultimate settlement. The Company’s policy is to recognize interest and penalties related to the underpayment of income taxes as a component of income tax expense or benefit. To date, there have been no interest or penalties charged in relation to the unrecognized tax benefits.

F-14

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

Foreign Currency

Assets and liabilities of non-U.S. subsidiaries that operate in a local currency environment, where the local currency is the functional currency, are translated to U.S. dollars at exchange rates in effect at the balance sheet date, with the resulting translation adjustments directly recorded to a separate component of accumulated other comprehensive loss. Income and expense accounts are translated at average exchange rates for the period. Transactions which are not in the functional currency of the entity are remeasured into the functional currency and gains or losses resulting from the remeasurement recorded in other income (expense).

Net Loss per Share

Basic net loss per share is calculated by dividing the net loss by the weighted-average number of shares of common stock outstanding during the period, without consideration for common stock equivalents. Shares of common stock into which pre-funded warrants may be exercised are considered outstanding for the purposes of computing basic net loss per share because the shares may be issued for little or no consideration, are fully vested and are exercisable after the original issuance date. Diluted net loss per share is the same as basic net loss per share, since the effects of potentially dilutive securities are antidilutive. In periods when we have incurred a net loss, options and warrants to purchase common stock are considered common stock equivalents, but have been excluded from the calculation of diluted net loss per share, as their effect is antidilutive.

3.Fair Value Measurements

Financial assets and liabilities are recorded at fair value. The carrying amount of certain financial instruments, including cash and cash equivalents, accounts receivable, accounts payable and accrued liabilities approximate fair value due to their relatively short maturities. Assets and liabilities recorded at fair value on a recurring basis in the balance sheets are categorized based upon the level of judgment associated with the inputs used to measure their fair values. Fair value is defined as the exchange price that would be received for an asset or an exit price that would be paid to transfer a liability in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants on the measurement date. The authoritative guidance on fair value measurements establishes a three-tier fair value hierarchy for disclosure of fair value measurements as follows:

Level 1—Inputs are unadjusted, quoted prices in active markets for identical assets or liabilities at the measurement date;

Level 2—Inputs are observable, unadjusted quoted prices in active markets for similar assets or liabilities, unadjusted quoted prices for identical or similar assets or liabilities in markets that are not active, or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the related assets or liabilities; and

Level 3—Unobservable inputs that are significant to the measurement of the fair value of the assets or liabilities that are supported by little or no market data.

The Company’s financial instruments consist of Level 1, Level 2, and Level 3 assets. Where quoted prices are available in an active market, securities are classified as Level 1. Money market funds and U.S. Government treasury bills are classified as Level 1. Level 2 assets consist primarily of corporate bonds, asset backed securities, commercial paper, U.S. Government Treasury and agency securities, and debt securities in government-sponsored entities based upon quoted market prices for similar movements in active markets, quoted prices for identical or similar instruments in markets that are not active and model-based valuation techniques for which all significant inputs are observable in the market or can be corroborated by observable market data for substantially the full term of the assets. Where applicable these models project future cash flows and discount the future amounts to a present value using market-based observable inputs obtained from various third-party data providers, including but not limited to, benchmark yields, interest rate curves, reported trades, broker/dealer quotes and reference data.

The Company determines the fair value of its equity investments in Solid Biosciences, Inc., or Solid, by using the quoted market prices, which are Level 1 fair value measurements.

F-15

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

The following tables set forth the fair value of the Company’s financial assets remeasured on a recurring basis based on the three-tier fair value hierarchy (in thousands):

	December 31, 2023
	Level 1		Level 2		Level 3		Total
Financial Assets:
Money market funds	$	162,289	$	—	$	—	$	162,289
Certificates of deposit and time deposits		—		17,986		—		17,986
Corporate bonds		—		215,166		—		215,166
Commercial paper		—		20,620		—		20,620
Asset-backed securities		—		2,712		—		2,712
U.S. Government Treasury and agency securities		57,437		259,605		—		317,042
Investment in Solid common stock		3,204		—		—		3,204
Deferred compensation assets		—		10,220		—		10,220
Total financial assets	$	222,930	$	526,309	$	—	$	749,239
Financial Liabilities:
Deferred compensation liabilities	$	—	$	10,365	$	—	$	10,365

	December 31, 2022
	Level 1		Level 2		Level 3		Total
Financial Assets:
Money market funds	$	102,847	$	—	$	—	$	102,847
Certificates of deposit and time deposits		—		25,972		—		25,972
Corporate bonds		—		427,598		—		427,598
Commercial paper		—		135,393		—		135,393
Asset-backed securities		—		11,980		—		11,980
U.S. Government Treasury and agency securities		27,645		129,345		—		156,990
Debt securities in government-sponsored entities		—		15,855		—		15,855
Investment in Solid common stock		2,807		—		—		2,807
Deferred compensation assets		—		4,575		—		4,575
Total financial assets	$	133,299	$	750,718	$	—	$	884,017
Financial Liabilities:
Deferred compensation liabilities	$	—	$	4,657	$	—	$	4,657

Deferred compensation assets are recorded at fair value in other non-current assets in the Consolidated Balance Sheets. There have been no significant gains or losses on deferred compensation assets for the periods presented.

Deferred compensation liabilities consist of short-term liabilities of $0.2 million and nil as of December 31, 2023 and 2022, respectively, included in accrued liabilities on the Consolidated Balance Sheets, and long-term liabilities of $10.1 million and $4.7 million as of December 31, 2023 and 2022, respectively, included in other non-current liabilities on the Consolidated Balance Sheets.

F-16

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

4.Balance Sheet Components

Cash Equivalents and Marketable Debt Securities

The fair values of cash equivalents and marketable debt securities classified as available-for-sale securities consisted of the following (in thousands):

	December 31, 2023
			Gross Unrealized
	Amortized Cost		Gains		Losses			Estimated Fair Value
Money market funds	$	162,289	$	—	$	—		$	162,289
Certificates of deposit and time deposits		17,986		—		—			17,986
Corporate bonds		214,792		711		(337	)		215,166
Commercial paper		20,620		—		—			20,620
Asset-backed securities		2,715		—		(3	)		2,712
U.S. Government Treasury and agency securities		316,160		982		(100	)		317,042
Total	$	734,562	$	1,693	$	(440	)	$	735,815

	December 31, 2022
			Gross Unrealized
	Amortized Cost		Gains		Losses			Estimated Fair Value
Money market funds	$	102,847	$	—	$	—		$	102,847
Certificates of deposit and time deposits		25,972		—		—			25,972
Corporate bonds		432,211		87		(4,700	)		427,598
Commercial paper		135,393		—		—			135,393
Asset-backed securities		12,002		—		(22	)		11,980
U.S. Government Treasury and agency securities		157,933		320		(1,263	)		156,990
Debt securities in government-sponsored entities		16,005		—		(150	)		15,855
Total	$	882,363	$	407	$	(6,135	)	$	876,635

At December 31, 2023, the remaining contractual maturities of available-for-sale securities were less than three years. There have been no significant realized gains or losses on available-for-sale securities for the periods presented.

Inventory

Inventory consists of the following (in thousands):

	December 31,
	2023		2022
Work-in-process	$	18,859	$	17,486
Finished goods		15,110		9,280
Total inventory	$	33,969	$	26,766

F-17

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

Property, Plant, and Equipment, net

Property, plant, and equipment, net consists of the following (in thousands):

		December 31,
	Useful life (years)	2023			2022
Building	20-30	$	181,356		$	2,798
Leasehold improvements	Shorter of lease term or estimated useful life		58,683			43,941
Research and development equipment	5		56,347			50,291
Furniture and office equipment	5		6,419			5,540
Computer equipment and software	3-5		16,196			13,876
Manufacturing equipment	5-15		37,297			570
Land	Not applicable		16,619			16,619
Construction-in-progress	Not applicable		867			189,448
Other	Varies by asset		183			24
Property, plant, and equipment, gross			373,967			323,107
Less: accumulated depreciation			(83,401	)		(63,381	)
Property, plant, and equipment, net		$	290,566		$	259,726

Depreciation expense for the years ended December 31, 2023, 2022, and 2021 was $22.2 million, $15.0 million and $12.9 million, respectively. Amortization of leasehold improvements and software is included in depreciation expense.

Construction in progress reflects amounts incurred for construction or improvements of property or costs for equipment that has not been placed in service. The construction-in-progress balance as of December 31, 2022 is primarily the construction costs for the gene therapy manufacturing facility in Bedford, Massachusetts.

Accrued Liabilities

Accrued liabilities consists of the following (in thousands):

	December 31,
	2023		2022
Research, clinical study, and manufacturing expenses	$	65,326	$	73,558
Payroll and related expenses		82,936		78,938
Other		48,224		52,182
Total accrued liabilities	$	196,486	$	204,678

5.Intangible Assets, net

Indefinite-lived Intangibles

The Company has IPR&D assets of $129.0 million as of December 31, 2023 and 2022. IPR&D assets represent the fair value of acquired programs to develop an AAV gene therapy for OTC deficiency and to develop an AAV gene therapy for glycogen storage disease type Ia. The fair value of IPR&D assets acquired was determined based on the discounted present value of each research project’s projected cash flows using an income approach, including the application of probability factors related to the likelihood of success of the program reaching final development and commercialization. Additionally, the projections consider the relevant market sizes and growth factors, estimated future cash flows from product sales resulting from completed products and in-process projects and timing and costs to complete the in-process projects. The rates utilized to discount the net cash flows to their present value are commensurate with the stage of development of the projects and uncertainties in the economic estimates used in the projections. IPR&D assets are considered to be indefinite-life until the completion or abandonment of the associated research and development efforts.

Finite-lived Intangibles

F-18

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

Subsequent to the FDA approval of Dojolvi for the treatment of LC-FAOD in 2020, the Company recorded $4.8 million for the attainment of various development and commercial milestones as finite-lived intangible assets which are amortized over a weighted-average useful life of 5.7 years.

In January 2022, the Company announced a collaboration with Regeneron to commercialize Evkeeza for HoFH outside of the U.S. Upon closing of the transaction in January 2022, the Company paid Regeneron a $30.0 million upfront payment. During the year ended December 31, 2023, a $10.0 million regulatory milestone was achieved. As both the upfront payment and the regulatory milestone are related to the Company’s use of intellectual property for Evkeeza for HoFH, these amounts were recorded as intangible assets, which are amortized over a weighted-average useful life of ten years.

The Company's intangible assets were as follows:

	December 31, 2023
	Gross Carrying Amount		Weighted-Average Life (Years)		Accumulated Amortization			Net Carrying Amount
Indefinite-lived intangibles	$	129,000		—	$	—		$	129,000
Finite-lived intangibles		44,775		9.6		(7,504	)		37,271
Total intangible assets	$	173,775		—	$	(7,504	)	$	166,271

	December 31, 2022
	Gross Carrying Amount		Weighted-Average Life (Years)		Accumulated Amortization			Net Carrying Amount
Indefinite-lived intangibles	$	129,000		—	$	—		$	129,000
Finite-lived intangibles		34,775		9.9		(3,670	)		31,105
Total intangible assets	$	163,775		—	$	(3,670	)	$	160,105

The Company recorded costs of sales of $3.8 million, $3.2 million and $0.3 million for the years ended December 31, 2023, 2022, and 2021, respectively, related to the amortization of the intangible assets.

The expected amortization of the intangible assets, as of December 31, 2023, for each of the next five years and thereafter is as follows:

2024	$	4,903
2025		4,903
2026		4,903
2027		4,462
2028		4,022
Thereafter		14,078
Total	$	37,271

F-19

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

6.Revenue

The following table disaggregates total revenues from external customers by product sales, royalty revenue, and collaboration and license revenue (in thousands):

	Year Ended December 31,
	2023		2022		2021
Product sales:
Crysvita	$	75,697	$	42,678	$	21,422
Mepsevii		30,441		20,637		16,035
Dojolvi		70,633		55,612		39,560
Evkeeza		3,642		—		—
Total product sales		180,413		118,927		77,017
Crysvita royalty revenue		182,652		21,692		17,951
Collaboration and license revenue:
Crysvita collaboration revenue in Profit-Share Territory		69,705		215,024		171,198
Crysvita royalty revenue in European Territory		—		—		244
Daiichi Sankyo		1,479		7,686		84,996
Total collaboration and license revenue		71,184		222,710		256,438
Total revenues	$	434,249	$	363,329	$	351,406

The following table disaggregates total revenues based on geographic location (in thousands):

	Year Ended December 31,
	2023		2022		2021
North America	$	307,149	$	281,088	$	301,110
Latin America		77,342		44,711		23,636
Europe		47,534		36,369		26,660
Japan		2,224		1,161		—
Total revenues	$	434,249	$	363,329	$	351,406

The following table presents the activity and ending balances for sales-related accruals and allowances (in thousands):

	Year Ended December 31,
	2023			2022			2021
Balance of product sales reserve at beginning of year	$	11,487		$	7,181		$	3,913
Provisions		18,761			13,525			9,586
Payments		(12,746	)		(9,613	)		(6,120	)
Adjustments		(473	)		394			(198	)
Balance of product sales reserve at end of year	$	17,029		$	11,487		$	7,181

The following table presents changes in the contract liabilities for the years ended December 31, 2023 and 2022 (in thousands):

	Year Ended December 31,
	2023			2022
Balance of contract liabilities at beginning of period	$	1,479		$	9,076
Additions		—			89
Deductions		(1,479	)		(7,686	)
Balance of contract liabilities at end of period, net	$	—		$	1,479

F-20

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

See Note 8 for additional details on contract liabilities activities.

The Company’s largest accounts receivable balance was from a collaboration partner and was 53% and 68% of the total accounts receivable balance as of December 31, 2023 and 2022, respectively.

7.GeneTx Acquisition

In August 2019, the Company entered into a Program Agreement and a Unitholder Option Agreement with GeneTx Biotherapeutics LLC, or GeneTx, to collaborate on the development of GeneTx’s GTX-102, an ASO for the treatment of Angelman syndrome. In July 2022, pursuant to the terms of the Unitholder Option Agreement, as amended, the Company exercised the option to acquire GeneTx and entered into a Unit Purchase Agreement, or the Purchase Agreement, pursuant to which the Company purchased all the outstanding units of GeneTx. In accordance with the terms of the Purchase Agreement, the Company paid the option exercise price of $75.0 million and an additional $15.6 million to acquire the outstanding cash of GeneTx, and adjustments for working capital and transaction expenses of $0.6 million, for a total purchase consideration of $91.2 million. The Company may be required to make payments of up to $190.0 million upon the achievement of certain milestones, including up to $30.0 million in milestone payments upon achievement of the earlier of initiation of a Phase 3 clinical study or product approvals in Canada and the U.K., up to $85.0 million in additional regulatory approval milestones for the achievement of U.S. and EU product approvals, and up to $75.0 million in commercial milestone payments based on annual worldwide net product sales. The Company will also pay tiered mid- to high single-digit percentage royalties based on licensed product annual net sales. If the Company receives and resells an FDA priority review voucher, or PRV, in connection with a new drug application approval, GeneTx is entitled to receive a portion of proceeds from the sale or a cash payment from the Company if the Company choses to retain the PRV. As part of the Company's acquisition of GeneTx, the Company assumed a License Agreement with Texas A&M University, or TAMU. Under this agreement, TAMU is eligible to receive from the Company up to $23.5 million upon the achievement of various future milestones, a nominal annual license fee that may increase up to a maximum of $2.0 million, as well as royalties in the mid-single-digits of net sales.

The transaction was accounted as an asset acquisition, as substantially all of the fair value of the gross assets acquired was concentrated in a single identifiable in-process research and development intangible asset. Prior to the achievement of certain development and regulatory milestones, the acquired in-process research and development intangible asset has not yet reached technological feasibility and has no alternative future use. Accordingly, the Company recorded the acquisition price of $75.0 million, net of cash and working capital acquired, as in-process research and development expense during the year ended December 31, 2022.

8.License and Research Agreements

Kyowa Kirin Co., Ltd.

In August 2013, the Company entered into a collaboration and license agreement with Kyowa Kirin Co., Ltd., or KKC. Under the terms of this collaboration and license agreement, as amended, the Company and KKC collaborate on the development and commercialization of Crysvita in the field of orphan diseases in the U.S. and Canada, or the Profit-Share Territory, and in the European Union, United Kingdom, and Switzerland, or the European Territory, and the Company has the right to develop and commercialize such products in the field of orphan diseases in Mexico and Central and South America, or Latin America.

Development Activities

In the field of orphan diseases, except for ongoing studies being conducted by KKC, the Company was the lead party for development activities in the Profit-Share Territory and in the European Territory until the applicable transition date. The Company shared the costs for development activities in the Profit-Share Territory and the European Territory conducted pursuant to the development plan before the applicable transition date equally with KKC. In April 2023, which was the transition date for the Profit-Share Territory, KKC became the lead party and became responsible for the costs of the subsequent development activities. However, the Company will continue to equally share in the costs of the studies with KKC that commenced prior to the applicable transition date.

The collaboration and license agreements are within the scope of ASC 808, which provides guidance on the presentation and disclosure of collaborative arrangements.

Collaboration and Royalty Revenue for Sales in the Profit-Share Territory

The Company and KKC shared commercial responsibilities and profits in the Profit-Share Territory until April 2023. Under the collaboration agreement, KKC manufactured and supplied Crysvita for commercial use in the Profit-Share Territory and charged the Company a transfer price of 30% of net sales in 2023, and 35% prior to December 31, 2022. The remaining profit or loss after supply

F-21

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

costs from commercializing products in the Profit-Share Territory was shared between the Company and KKC on a 50/50 basis until April 2023. In April 2023, commercialization responsibilities for Crysvita in the Profit-Share Territory transitioned to KKC. Thereafter, the Company is entitled to receive a tiered double-digit revenue share from the mid-20% range up to a maximum rate of 30%.

In 2022, the Company entered into an amendment to the collaboration agreement which granted the Company the right to continue to support KKC in commercial field activities in the U.S. through April 2024, subject to the limitations and conditions set forth in the amendment. The parties subsequently mutually agreed to extend the Company's right to continue to support KKC in commercial field activities in the U.S. through December 31, 2024, and as a result, the Company will continue to support commercial field efforts in the U.S. through a cost share arrangement through December 2024. After December 31, 2024, the Company’s rights to promote Crysvita in the U.S. will be limited to medical geneticists and the Company will solely bear its expenses for the promotion of Crysvita in the Profit-Share Territory.

As KKC was the principal in the sale transaction with the customer during the profit-share period, the Company recognized a pro-rata share of collaboration revenue, net of transfer pricing, in the period the sale occurs. The Company concluded that its portion of KKC’s sales in the Profit-Share Territory prior to April 2023 was analogous to a royalty and therefore recorded its share as collaboration revenue, similar to a royalty. Starting in April 2023, the Company began to record the royalty revenue as the underlying sales occur.

In July 2022, the Company sold to OMERS its right to receive 30% of the future royalty payments due to the Company based on net sales of Crysvita in the U.S. and Canada, subject to a cap, beginning in April 2023, as further described in Note 10. The Company records this revenue as royalty revenue.

Product Sales Revenue for Other Territories

The Company is responsible for commercializing Crysvita in Latin America and Turkey. The Company is considered the principal in these territories as the Company controls the product before it is transferred to the customer. Accordingly, the Company records revenue on a gross basis for the sale of Crysvita once the product is delivered and the risk and title of the product is transferred to the distributor. KKC has the option to assume responsibility for commercialization efforts in Turkey from the Company, after a certain minimum period.

Under the collaboration agreement, KKC manufactures and supplies Crysvita, which is purchased by the Company for sales in Latin American territories and charges the Company a transfer price of 30% of net sales. The transfer price on these sales was 35% prior to December 31, 2022. The Company also pays to KKC a low single-digit royalty on net sales in Latin America.

Total Crysvita revenue was as follows (in thousands):

	Year Ended December 31,
	2023		2022		2021
Revenue in profit-share territory:
Collaboration revenue	$	69,705	$	215,024	$	171,198
Royalty revenue		113,288		—		—
Non-cash royalty revenue		48,581		—		—
Total revenue in Profit-Share Territory		231,574		215,024		171,198
Product sales		75,697		42,678		21,422
Royalty revenue in European Territory		—		—		244
Non-cash royalty revenue in European Territories		20,783		21,692		17,951
Total Crysvita revenue	$	328,054	$	279,394	$	210,815

Royalty Revenue for Sales in the European Territory

KKC has the commercial responsibility for Crysvita in the European Territory. In December 2019, the Company sold its right to receive royalty payments based on sales in the European Territory to Royalty Pharma, effective January 1, 2020, as further described in Note 10. Prior to the Company’s sale of the royalty, the Company received a royalty of up to 10% on net sales in the European Territory, which was recognized as the underlying sales occur. Beginning in 2020, the Company records the royalty revenue as non-cash royalty revenues. The Company records this revenue as royalty revenue.

F-22

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

Collaboration Cost Sharing and Payments

Under the collaboration agreement, KKC and the Company share certain development and commercialization costs and as a result, the Company was reimbursed for these costs and operating expenses were reduced. Additionally, KKC is owed a transfer price fee and royalties on certain revenues and the Company recorded amounts owed to KKC in cost of sales. These amounts were recognized in the Company’s Statements of Operations in connection with the collaboration agreement with KKC as follows (in thousands):

	Year Ended December 31,
	2023			2022			2021
Research and development	$	(6,510	)	$	(15,974	)	$	(21,657	)
Selling, general and administrative	$	(17,199	)	$	(37,217	)	$	(32,629	)
Cost of sales	$	18,476		$	13,250		$	6,701

Collaboration Receivable and Payable

The Company had accounts receivable from KKC in the amount of $39.2 million and $27.5 million from profit-share revenue and royalties and other receivables recorded in other current assets of $1.1 million and $6.4 million and accrued liabilities of $5.3 million and $3.1 million from commercial and development activity reimbursements, as of December 31, 2023 and 2022, respectively.

Saint Louis University

In November 2010, the Company entered into a license agreement with Saint Louis University, or SLU. Under the terms of this license agreement, SLU granted the Company an exclusive worldwide license to make, have made, use, import, offer for sale, and sell therapeutics related to SLU’s beta-glucuronidase product for use in the treatment of human diseases.

The Company made a milestone payment of $0.1 million upon approval of Mepsevii for treatment of MPS 7. The Company is required to pay to SLU a low single-digit royalty on net sales of the licensed products in any country or region, upon reaching a certain level of cumulative worldwide sales of the product.

Baylor Research Institute

In September 2012, the Company entered into a license agreement with Baylor Research Institute, or BRI. Under the terms of this license agreement, as amended, BRI exclusively licensed to the Company its territories for certain intellectual property related to Dojolvi (triheptanoin) for the treatment of LC-FAOD.

For the years ended December 31, 2023 and 2022, the Company recorded nil and $2.5 million, respectively, for the attainment of various development and commercial milestones as finite-lived intangible assets. The Company is obligated to make additional future payments of up to $7.5 million contingent upon attainment of various development and commercial milestones. Additionally, the Company is paying BRI a mid- single-digit royalty on net sales of the licensed product in the licensed territories.

REGENXBIO, Inc.

The Company has a license agreement with REGENXBIO, Inc., or REGENX, for an exclusive, sublicensable, worldwide commercial license under certain intellectual property for preclinical and clinical research and development, and commercialization of drug therapies using REGENX's licensed patents for the treatment of hemophilia A, OTC deficiency, and GSD1a. The Company will pay an annual fee and certain milestone fees per disease indication, low to mid- single-digit royalty percentages on net sales of licensed products, and milestone and sublicense fees owed by REGENX to its licensors, contingent upon the attainment of certain development activities as outlined in the agreement.

The Company also has an option and license agreement with REGENX under which the Company has an exclusive, sublicensable, worldwide license to make, have made, use, import, sell, and offer for sale licensed products to treat Wilson disease and CDKL5 deficiency. For each disease indication, the Company is obligated to pay an annual maintenance fee of $0.1 million and up to $9.0 million upon achievement of various milestones, as well as mid- to high single-digit royalties on net sales of licensed products and mid- single-digit to low double-digit percentage sublicenses fees, if any.

In March 2020, the Company entered into a license agreement with REGENX, for an exclusive, sublicensable, worldwide license to REGENX’s NAV AAV8 and AAV9 vectors for the development and commercialization of gene therapy treatments for a rare metabolic disorder. In return for these rights, the Company made an upfront payment of $7.0 million. The Company will pay certain

F-23

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

annual fees of $0.1 million, milestone payments of up to $14.0 million, and royalties on any net sales of products incorporating the licensed intellectual property that range from a high single-digit to low double-digit royalty.

Bayer HealthCare LLC

The Company previously had a collaboration and license agreement with Bayer Healthcare LLC, or Bayer, to research, develop and commercialize AAV gene therapy products for the treatment of hemophilia A, or DTX 201. Under this agreement, Bayer had been granted an exclusive license to develop and commercialize one or more novel gene therapies for hemophilia A.

In October 2022, the Collaboration and License Agreement for DTX201 with Bayer was terminated and all licensed rights to DTX201 have reverted back to the Company. The Company also obtained rights to all necessary data and information to further develop DTX201 or another hemophilia A program through a royalty-free, worldwide, sublicensable, perpetual license.

University of Pennsylvania

The Company has a research, collaboration, and license agreement with University of Pennsylvania School of Medicine, or Penn, which provides the terms for the Company and Penn to collaborate with respect to the pre-clinical development of gene therapy products for the treatment of certain indications. Under the agreement, Penn granted the Company an exclusive, worldwide license to certain patent rights arising out of the research program, subject to certain retained rights, and a non-exclusive, worldwide license to certain Penn intellectual property, in each case to research, develop, make, have made, use, sell, offer for sale, commercialize and import licensed products in each indication for the term of the agreement. The Company will fund the cost of the research program in accordance with a mutually agreed-upon research budget and will be responsible for clinical development, manufacturing and commercialization of each indication. The Company may be obligated to make milestone payments of up to $5.0 million for each indication, if certain development milestones are achieved over time. The Company is also obligated to make milestone payments of up to $25.0 million per approved product if certain commercial milestones are achieved, as well as low to mid- single-digit royalties on net sales of each licensed product.

Arcturus Therapeutics Holdings Inc.

In October 2015, the Company entered into a Research Collaboration and License Agreement with Arcturus Therapeutics Holdings Inc., or Arcturus, to collaborate on the research and development of therapies for select rare diseases. Arcturus was responsible for conducting certain research services, funded by the Company, and the Company was responsible for development and commercialization costs.

On a product-by-product basis, the Company is obligated to make development and regulatory milestone payments of up to $24.5 million, and commercial milestone payments of up to $45.0 million if certain milestones are achieved. For the year ended December 31, 2021, the Company achieved a $1.0 million development milestone, which was paid with a corresponding credit received from Arcturus for prior research and collaboration activities. The Company is also obligated to pay Arcturus royalties on any net sales of products incorporating the licensed intellectual property that may range from a mid- single-digit to low double-digit percentage. There were no material expenses for this arrangement during the years ended December 31, 2023, 2022, and 2021.

In June 2019, the Company entered into an Equity Purchase Agreement and an amendment to the Research Collaboration and License Agreement, or License Agreement, to expand the field of use and increase the number of disease targets to include mRNA, DNA and siRNA therapeutics for up to 12 rare diseases. Pursuant to the agreements, the Company paid $6.0 million in cash upfront to Arcturus and purchased 2,400,000 shares of Arcturus’ common stock at a stated value of $10.00 per share, resulting in a total of $30.0 million of consideration paid at the close of the transaction. As a result, the Company received expanded license rights under the License Agreement, Arcturus common stock, and an option to purchase an additional 600,000 shares of Arcturus’ common stock at $16.00 per share. In May 2020, the Company exercised its option to purchase 600,000 shares of Arcturus common stock for a total purchase price of $9.6 million.

The Company’s investment in Arcturus was accounted at fair value, as the fair value was readily determinable. During the year ended December 31, 2022, the Company sold 500,000 shares of Arcturus common stock, at a weighted-average price of $20.39 per share. As of December 31, 2022, the Company held no shares of Arcturus common stock.

F-24

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

The changes in the fair value of the Company’s equity investment in Arcturus were as follows (in thousands):

	Arcturus Common Stock
December 31, 2021	$	18,505
Change in fair value		(8,411	)
Sale of shares		(10,094	)
December 31, 2022	$	—

Daiichi Sankyo

In March 2020, the Company executed a License and Technology Access Agreement, or the License Agreement, with Daiichi Sankyo Co., Ltd., or Daiichi Sankyo. Pursuant to the License Agreement, the Company granted Daiichi Sankyo a non-exclusive license to intellectual property, including know-how and patent applications, with respect to its Pinnacle PCLTM producer cell line platform, or Pinnacle PCL Platform, and HEK293 transient transfection manufacturing technology platforms for AAV-based gene therapy products.

Under the terms of the License Agreement, Daiichi Sankyo made an upfront payment of $125.0 million and an additional $25.0 million upon completion of the technology transfer of the Pinnacle PCL Platform and HEK293 platform. Daiichi Sankyo reimbursed the Company for all costs associated with the transfer of the manufacturing technology.

The Company also entered into a Stock Purchase Agreement, or SPA, with Daiichi Sankyo, pursuant to which Daiichi Sankyo purchased 1,243,913 shares of the Company’s common stock in exchange for $75.0 million in cash during the first quarter of 2020. The fair market value of the common stock issued to Daiichi Sankyo was $55.3 million based on the stock price of $44.43 per share on the date of issuance, resulting in a $19.7 million premium on the SPA.

In June 2020, the Company executed a subsequent license agreement, or the Sublicense Agreement, with Daiichi Sankyo for transfer of certain technology in consideration for an upfront payment of $8.0 million and annual maintenance fees, milestone payments, and royalties on any net sales of products incorporating the licensed intellectual property.

The Company evaluated the License Agreement and the Sublicense Agreement under ASC 606 and determined that the performance obligations under the agreements are (i) intellectual property with respect to its Pinnacle PCL Platform and HEK293 transient transfection manufacturing technology platform together with the initial technical assistance and technology transfer services, and (ii) the transfer of any know-how and improvements after the completion of the initial technology transfer through the end of the three year technology transfer period.

The Company allocated the total transaction price to the two performance obligations on a relative stand-alone selling price basis. Revenue allocated to the intellectual property and the technology transfer services was recognized over an initial period which was completed during the first quarter of 2022, measuring the progress toward complete satisfaction of the individual performance obligation using an input measure. Revenue for know-how and improvements after the completion of technology transfer was recognized on a straight-line basis over the remaining technology transfer period, which ended in March 2023, as it was expected that Daiichi Sankyo would receive and consume the benefits consistently throughout the period. The Company’s current obligations under the License Agreement and the Sublicense Agreement were completed following the conclusion of the technology transfer period. Total revenue recognized under the arrangement through December 31, 2023 was $183.3 million.

The Company recognized $1.5 million, $7.7 million, and $85.0 million for the years ended December 31, 2023, 2022, and 2021, respectively, in revenue related to this arrangement. Accordingly, the Company recorded contract liabilities of nil and $1.5 million, net, for this arrangement as of December 31, 2023 and 2022, respectively.

Mereo

In December 2020, the Company entered into a License and Collaboration Agreement with Mereo to collaborate on the development of setrusumab. Under the terms of the agreement, the Company will lead future global development of setrusumab in both pediatric and adult patients with OI. The Company was granted an exclusive license to develop and commercialize setrusumab in the U.S., Turkey, and the rest of the world, excluding the European Economic Area, United Kingdom, and Switzerland, or the

F-25

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

Mereo Territory, where Mereo retains commercial rights. Each party will be responsible for post-marketing commitments and commercial supply in their respective territories.

Upon the closing of the transaction in January 2021, the Company made a payment of $50.0 million to Mereo and will be required to make payments of up to $254.0 million upon the achievement of certain clinical, regulatory, and commercial milestones. The Company will pay for all global development costs as well as tiered double-digit percentage royalties to Mereo on net sales in the U.S., Turkey, and the rest of the world (excluding the Mereo Territory), and Mereo will pay the Company a fixed double-digit percentage royalty on net sales in the Mereo Territory.

Although Mereo is a variable interest entity, the Company is not the primary beneficiary as it does not have the power to direct the activities that would most significantly impact the economic performance of Mereo. Prior to the achievement of certain development milestones, all consideration paid to Mereo represents rights to potential future benefits associated with Mereo’s in-process research and development activities, which have not reached technological feasibility and have no alternative future use.

For the years ended December 31, 2023, 2022, and 2021, the Company recorded research and development expense of $9.0 million for the achievement of a clinical milestone, nil, and $50.0 million for the upfront payment, respectively.

Regeneron

In January 2022, the Company announced a collaboration with Regeneron Pharmaceuticals, or Regeneron, to commercialize Evkeeza for HoFH outside of the U.S. Evkeeza is approved in the U.S., where it is marketed by Regeneron, and in the EU and U.K. as a first-in-class therapy for use together with diet and other low-density lipoprotein-cholesterol-lowering therapies to treat adults and adolescents aged 12 years and older with HoFH. Pursuant to the terms of the agreement, the Company received the rights to develop, commercialize and distribute the product for HoFH in countries outside of the U.S. The Company is obligated to pay up to $63.0 million in future milestone payments, contingent upon the achievement of certain regulatory and sales milestones. The Company may share in certain costs for global trials led by Regeneron and also received the right to opt into other potential indications.

The collaboration agreement is within the scope of ASC 808 which provides guidance on the presentation and disclosure of collaborative arrangements. As the Company would be the principal in future sale transactions with the customer, the Company will recognize product sales and cost of sales in the period the related sales occur and the related revenue recognition criteria are met. Under the collaboration agreement, Regeneron supplies the product and charges the Company a transfer price from the low 20% range up to 40% on net sales, which is recognized as cost of sales in the Company’s Statement of Operations.

The Company paid Regeneron a $30.0 million upfront payment upon the closing of the transaction in January 2022, and during the year ended December 31, 2023, a $10.0 million regulatory milestone was achieved. As these payments are for the Company’s use of intellectual property for Evkeeza for HoFH, they were recorded as intangible assets. See Note 5 for additional details.

Under the collaboration agreement, the Company reimbursed Regeneron for development costs of $7.6 million, $7.3 million, and nil for the years ended December 31, 2023, 2022, and 2021, respectively, which were recorded as research and development expense on the Consolidated Statements of Operations. The Company had collaboration payables for this arrangement included in accrued liabilities on the Consolidated Balance Sheets of $10.6 million and $6.8 million as of December 31, 2023 and December 31, 2022, respectively. Additionally, Regeneron is owed a transfer price fee and royalties on certain revenues and the Company recorded amounts owed to Regeneron of $0.7 million in cost of sales on the Consolidated Statements of Operations for the year ended December 31, 2023.

Abeona

In May 2022, the Company announced an exclusive License Agreement for the AAV gene therapy for UX111 with Abeona for the treatment of MPS IIIA. Under the terms of the agreement, the Company assumed responsibility for the UX111 program and in return, Abeona is eligible to receive tiered royalties of up to 10% on net sales and commercial milestone payments of up to $30.0 million following regulatory approval of the product. Additionally, the Company entered into an Assignment and Assumption Agreement with Abeona to transfer and assign to the Company the exclusive license agreement between Nationwide Children’s Hospital, or NCH, and Abeona for certain rights related to UX111. Under this agreement, NCH is eligible to receive from the Company up to $1.0 million in development and regulatory milestones as well as royalties in the low single-digits of net sales.

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ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

The Company is obligated to pay Abeona certain prior development costs and other transition costs related to UX111. Prior to product regulatory approval, all consideration paid to Abeona represents rights to potential future benefits associated with Abeona’s in-process research and development activities, which have not reached technological feasibility and have no alternative future use. Accordingly, the value of the acquired intellectual property rights and clinical inventory as well as prior development costs and transition costs of $3.1 million, were recorded as research and development expense for the year ended December 31, 2022. The Company did not incur any other material costs related to this agreement in the years presented.

Solid Biosciences, Inc.

In October 2020, the Company entered into a strategic Collaboration and License Agreement with Solid Biosciences Inc., or Solid, and received an exclusive license for any pharmaceutical product that expresses Solid’s proprietary microdystrophin construct from AAV8 and variants thereof in clade E for use in the treatment of Duchenne muscular dystrophy and other diseases resulting from lack of functional dystrophin, including Becker muscular dystrophy. The Company is collaborating to develop products that combine Solid’s differentiated microdystrophin construct, the Company’s Pinnacle PCL Platform, and the Company’s AAV8 variants. Solid is providing development support and was granted an exclusive option to co-invest in products the Company develops for profit-share participation in certain territories. On a product-by-product basis, the Company is obligated to make development milestone payments of up to $25.0 million, regulatory milestone payments of up to $65.0 million, and commercial milestone payments of up to $165.0 million, if such milestones are achieved, as well as royalties on any net sales of products incorporating the licensed intellectual property that range from a low to mid-double-digit percentage. The royalty rate changes to mid- to high double-digit percentage if Solid decides to co-invest in the product.

The Company also entered into a Stock Purchase Agreement and the Investor Agreement with Solid, pursuant to which, the Company purchased 7,825,797 shares of Solid’s common stock for an aggregate purchase price of $40.0 million. In October 2022, Solid announced a 1 for 15 reverse stock split. After the split, the Company held 521,719 shares of Solid's common stock. The Company’s investment in Solid is being accounted at fair value, as the fair value is readily determinable. The Company recorded the common stock investment at $26.8 million on the transaction date, which was based on the quoted market price on the closing date.

Although Solid is a variable interest entity, the Company is not the primary beneficiary as it does not have the power to direct the activities that would most significantly impact the economic performance of Solid. Prior to the achievement of certain development milestones, all consideration paid to Solid represents rights to potential future benefits associated with Solid’s in-process research and development activities, which have not reached technological feasibility and have no alternative future use. Accordingly, the remaining $13.2 million of the total $40.0 million paid as consideration was attributed to the license rights obtained and was recorded as in-process research and development expense during the year ended December 31, 2020.

The changes in the fair value of the Company’s investment in Solid’s common stock were as follows (in thousands):

	Solid Common Stock
December 31, 2021	$	13,695
Change in fair value		(10,888	)
December 31, 2022		2,807
Change in fair value		397
December 31, 2023	$	3,204

9.Leases

The Company leases office space and research, testing and manufacturing laboratory space in various facilities in Novato and Brisbane, California, in Somerville, and Woburn, Massachusetts, and in certain foreign countries, under operating agreements expiring at various dates through 2029. Certain lease agreements include options for the Company to extend the lease for multiple renewal periods and provide for annual minimum increases in rent, usually based on a consumer price index or annual minimum increases. None of these optional periods have been considered in the determination of the right-of-use lease asset or the lease liability for the leases as the Company did not consider it reasonably certain that it would exercise any such options. The Company recognizes lease expense on a straight-line basis over the non-cancelable term of its operating leases. The variable lease expense primarily consists of common area maintenance and other operating costs.

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ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

The components of lease expense were as follows (in thousands):

	Year Ended December 31,
	2023		2022		2021
Operating lease expense	$	12,883	$	11,775	$	11,209
Variable lease expense		5,272		4,785		4,142
Financing:
Amortization		203		343		310
Interest expense		—		37		58
Total	$	18,358	$	16,940	$	15,719

Cash paid for amounts included in the measurement of operating lease liabilities for the years ended December 31, 2023, 2022, and 2021 was $13.4 million, $13.1 million, and $11.8 million, respectively, and was included in net cash used in operating activities in the Consolidated Statements of Cash Flows.

Right-of-use lease assets were $23.9 million and $26.0 million as of December 31, 2023 and 2022, respectively, and were included in other non-current assets on the Consolidated Balance Sheets.

The following table summarizes maturities of lease liabilities and the reconciliation of lease liabilities as of December 31, 2023:

Year Ending December 31,	Operating
2024	$	16,234
2025		11,932
2026		8,430
2027		5,867
2028		5,887
Thereafter		6,009
Total future lease payments		54,359
Less: Amount representing interest		(11,190	)
Present value of future lease payments		43,169
Less: Lease liabilities, current		(12,595	)
Lease liabilities, non-current	$	30,574

Lease liabilities are based on the net present value of the remaining lease payments over the remaining lease term. For the years ended December 31, 2023 and 2022, the weighted-average remaining operating lease terms were 4.5 years and 3.0 years, the weighted-average remaining financing lease terms were nil and 2.8 years, the weighted-average discount rates used to determine the lease liability for operating leases were 9.6% and 6.7%, and the weighted-average discount rates used to determine the lease liability for finance leases were nil and 5.1% respectively.

10.Liabilities for Sales of Future Royalties

In December 2019, the Company entered into a Royalty Purchase Agreement with RPI. Pursuant to the agreement, RPI paid $320.0 million to the Company in consideration for the right to receive royalty payments effective January 1, 2020, arising from the net sales of Crysvita in the EU, the U.K., and Switzerland under the terms of the Company’s Collaboration and License Agreement with KKC dated August 29, 2013, as amended, or the KKC Collaboration Agreement. The agreement with RPI will automatically terminate, and the payment of royalties to RPI will cease, in the event aggregate royalty payments received by RPI are equal to or greater than $608.0 million prior to December 31, 2030, or in the event aggregate royalty payments received by RPI are less than $608.0 million prior to December 31, 2030, or when aggregate royalty payments received by RPI are equal to $800.0 million.

In July 2022, the Company entered into a Royalty Purchase Agreement with OMERS. Pursuant to the agreement, OMERS paid $500.0 million to the Company in consideration for the right to receive 30% of the future royalty payments due to the Company from KKC based on net sales of Crysvita in the U.S. and Canada under the terms of the KKC Collaboration Agreement. The calculation of royalty payments to OMERS is based on net sales of Crysvita beginning in April 2023 and will expire upon the earlier of the date on which aggregate payments received by OMERS equals $725.0 million or the date the final royalty payment is made to the Company under the KKC Collaboration Agreement.

Proceeds from these transactions were recorded as liabilities for sales of future royalties on the Consolidated Balance Sheets. Upon inception of the respective arrangements, the Company recorded $320.0 million and $500.0 million, net of transaction costs of $5.8 million and $9.1 million for RPI and OMERS, respectively, using the effective interest method over the estimated life of the applicable arrangement. In order to determine the amortization of the liabilities, the Company is required to estimate the total

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ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

amount of future royalty payments to be received by the Company and paid to RPI and OMERS, subject to the capped amount, over the life of the arrangements. The excess of future estimated royalty payments (subject to the capped amount) to RPI and OMERS, over the $314.2 million and $491.0 million, respectively, of net proceeds, is recorded as non-cash interest expense over the life of the arrangements. Consequently, the Company estimates an imputed interest on the unamortized portion of the liabilities and records interest expense relating to the transactions. The Company records the royalty revenue arising from the net sales of Crysvita in the applicable territories as royalty revenue in the Consolidated Statements of Operations over the term of the arrangements. Royalties earned under the RPI and OMERS arrangements from inception to December 31, 2023 have been $73.4 million and $48.6 million, respectively.

The Company periodically assesses the expected royalty payments using a combination of historical results, internal projections and forecasts from external sources. To the extent such payments are greater or less than the Company’s initial estimates or the timing of such payments is materially different than its original estimates, the Company will prospectively adjust the amortization of the liabilities and the effective interest rate. The Company’s effective annual interest rates were 6.2% and 7.8%, for RPI and OMERS, respectively, as of December 31, 2023.

There are a number of factors that could materially affect the amount and timing of royalty payments from KKC in the applicable territories, most of which are not within the Company’s control. Such factors include, but are not limited to, the success of KKC’s sales and promotion of Crysvita, changing standards of care, macroeconomic and inflationary pressures, the introduction of competing products, pricing for reimbursement in various territories, manufacturing or other delays, intellectual property matters, adverse events that result in governmental health authority imposed restrictions on the use of Crysvita, significant changes in foreign exchange rates as the royalty payments are made in U.S. dollars, or USD, while significant portions of the underlying sales of Crysvita are made in currencies other than USD, and other events or circumstances that could result in reduced royalty payments from sales of Crysvita, all of which would result in a reduction of royalty revenue and the non-cash interest expense over the life of the arrangement. Conversely, if sales of Crysvita in the relevant territories are more than expected, the royalty revenue and the non-cash interest expense recorded by the Company would be greater over the term of the arrangements.

The following table shows the activity within the liability account (in thousands):

	Liabilities for Sales of Future Royalties
	RPI			OMERS			Total
December 31, 2021	$	351,786		$	—		$	351,786
Net proceeds from sale of future    royalties		—			490,950			490,950
Royalty revenue		(21,692	)		—			(21,692	)
Non-cash interest expense		35,095			19,300			54,395
December 31, 2022		365,189			510,250			875,439
Royalty revenue		(20,783	)		(38,524	)		(59,307	)
Non-cash interest expense		32,235			43,200			75,435
December 31, 2023	$	376,641		$	514,926		$	891,567

11.Equity

At-the-Market Offerings

In May 2021, the Company entered into an Open Market Sale Agreement with Jefferies LLC, or Jefferies, pursuant to which the Company may offer and sell shares of the Company’s common stock having an aggregate offering proceeds up to $350.0 million, from time to time, in at-the-market, or ATM, offerings through Jefferies. During the year ended December 31, 2023, there were 1,175,584 shares sold under the ATM resulting in net proceeds of $53.3 million. There were no shares sold under the ATM for year ended December 31, 2022. As of December 31, 2023, the Company has sold a total of 2,225,956 shares under the ATM, resulting in net proceeds of $132.2 million.

Underwritten Public Offering

In October 2023, the Company completed an underwritten public offering in which 9,833,334 shares of common stock were sold, including the exercise in full by the underwriters of their option to purchase an additional 1,500,000 shares, at a public offering price of $30.00 per share. In connection with the offering, the Company sold to certain investors pre-funded warrants, in lieu of common stock, to purchase 1,666,722 shares of common stock at a purchase price of $29.999 per pre-funded warrant, which equals the public offering price per share of common stock less the $0.001 exercise price per share of each pre-funded warrant. The total

F-29

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

proceeds that the Company received from the offering were $326.5 million, net of underwriting discounts and commissions. As of December 31, 2023, none of the pre-funded warrants had been exercised.

The pre-funded warrants were classified as a component of permanent equity in the Company's Consolidated Balance Sheets as they are freestanding financial instruments that are immediately exercisable, do not embody an obligation for the Company to repurchase its own shares and permit the holders to receive a fixed number of shares of common stock upon exercise. All of the shares underlying the pre-funded warrants have been included in the weighted-average number of shares of common stock used to calculate net loss per share, basic and diluted, attributable to common stockholders because the shares may be issued for little or no consideration, are fully vested, and are exercisable after the original issuance date of the pre-funded warrants.

12.Stock-Based Awards

Equity Plan Awards

In 2014, the Company adopted the 2014 Incentive Plan, or the 2014 Plan, for the granting of stock-based awards to employees, directors, and consultants under terms and provisions established by the board of directors. The 2014 Plan had 2,250,000 shares of common stock available for future issuance at the time of its inception. The 2014 Plan provided for automatic annual increases in shares available for grant, beginning on January 1, 2015 through June 7, 2023. In June 2023, the Company adopted the 2023 Incentive Plan which had 4,500,000 shares of common stock available for future issuance at the time of its inception, plus the number of shares subject to the 2014 Plan cancelled after June 7, 2023. No further shares were granted under the 2014 Plan after June 7, 2023.In February 2021, the Company adopted the Employment Inducement Plan, or the Inducement Plan, which was subsequently amended in June 2023 to provide for a maximum of 850,000 shares available for grant under the plan. In 2014, the Company adopted the 2014 Incentive Plan, or the 2014 Plan, for the granting of stock-based awards to employees, directors, and consultants under terms and provisions established by the board of directors. Under the terms of the 2023 Plan and Inducement Plan, awards may be granted at an exercise price not less than fair market value. The exercise price of an option may not be less than the fair market value. The term of an award granted under the 2023 Plan and Inducement Plan may not exceed ten years. Typically, the vesting schedule for option grants to the employees provides that ¼ of the grant vests upon the first anniversary of the date of grant, with the remainder of the shares vesting monthly thereafter at a rate of 1/48 of the total shares subject to the option. Typically, the vesting schedule for RSU grants provides that ¼ of the grant vests upon the annual anniversary of the date of grant over the period of four years.

As of December 31, 2023, an aggregate of 19,610,125 shares of common stock have been authorized for issuance under the 2014 Plan, the 2023 Plan, and the Inducement Plan.

Stock Option Activity

The following table summarizes activity under the Company’s stock option plans and related information:

	Options Outstanding
	Number of Options			Weighted- Average Exercise Price		Weighted-Average Remaining Contractual Term (Years)	Aggregate Intrinsic Value
							(In thousands)
Outstanding — December 31, 2022		7,773,367		$	72.56	6.60	$	8,476
Options granted		2,123,256			45.05
Options exercised		(209,793	)		13.07
Options cancelled		(899,118	)		71.56
Outstanding — December 31, 2023		8,787,712			67.43	6.39		7,558
Vested and exercisable — December 31, 2023		5,415,110			73.28	4.96		1,214
Vested and expected to vest — December 31, 2023		8,461,973			67.96	6.29		6,794

The aggregate intrinsic values of options outstanding, vested and exercisable, and vested and expected to vest were calculated as the difference between the exercise price of the options and the fair value of the Company’s common stock. The total intrinsic value of options exercised during the years ended December 31, 2023, 2022, and 2021 was $4.9 million, $2.6 million, and $38.8 million, respectively. Cash received from the exercise of options was $2.7 million, $6.2 million, and $36.6 million for the years ended December 31, 2023, 2022, and 2021, respectively.

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ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

The weighted-average estimated fair value of stock options granted was $25.53, $34.77, and $70.84 per share of the Company’s common stock during the years ended December 31, 2023, 2022, and 2021, respectively. The total estimated grant date fair value of options vested during the years ended December 31, 2023, 2022, and 2021 was $59.7 million, $58.7 million, and $48.1 million, respectively.

Performance Stock Options

The following table summarizes activity under the Company’s Performance Stock Option, or PSO, plans and related information:

	PSOs Outstanding
	Number of Options			Weighted- Average Exercise Price		Weighted-Average Remaining Contractual Term (Years)		Aggregate Intrinsic Value
Outstanding — December 31, 2022		1,624,599		$	67.37		4.14	$	—
PSOs cancelled		(243,601	)		67.37
Outstanding — December 31, 2023		1,380,998			67.37		3.15		—
Vested and exercisable — December 31, 2023		117,865			67.37		3.09		—
Vested and expected to vest — December 31, 2023		983,173			67.37		3.14		—

During the year ended December 31, 2022, PSOs were granted to certain nonexecutive employees. PSOs are subject to vest only if specified operational milestones are achieved and the employees’ continued service with the Company. The Company uses the Black-Scholes method to calculate the fair value at the grant date and is recognizing stock-based compensation expense for the PSOs that are expected to vest. Stock-based compensation for PSOs is recognized over the service period, beginning in the period the Company determines it is probable that a milestone will be achieved. Forfeitures of PSOs are recognized as they occur. The Company reassesses the probability of the performance condition at each reporting period and adjusts the compensation cost based on the probability assessment. As of December 31, 2023, certain operational milestones were deemed probable of achievement. The aggregate intrinsic values of PSOs outstanding, vested and exercisable, and vested and expected to vest were calculated as the difference between the exercise price of the PSOs and the fair value of the Company’s common stock. The total estimated grant date fair value of PSOs vested during the year ended December 31, 2023, was $3.4 million. No PSOs were granted or were exercised during the year ended December 31, 2023. The weighted-average estimated fair value of PSOs granted was $28.76 during the year ended December 31, 2022.

Restricted Stock Units

The following table summarizes activity under the Company’s Restricted Stock Units, or RSU, plans and related information:

	RSUs Outstanding
	Number of Shares			Weighted- Average Grant Date Fair Value
Unvested — December 31, 2022		2,129,153		$	75.11
RSUs granted		2,447,170			44.52
RSUs vested		(738,130	)		73.99
RSUs cancelled		(394,081	)		61.22
Unvested — December 31, 2023		3,444,112			55.21

The fair value of the RSUs is determined on the grant date based on the fair value of the Company’s common stock. The fair value of the RSUs is recognized as expense ratably over the vesting period of one to four years. The total grant date fair value of the RSUs vested during the years ended December 31, 2023, 2022, and 2021 was $54.6 million, $47.1 million, and $35.5 million, respectively. The aggregate intrinsic value of the shares of the RSUs vested during the years ended December 31, 2023, 2022, and 2021 was $33.0 million, $37.8 million, and $69.9 million, respectively.

F-31

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

Performance Stock Units

The following table summarizes activity under the Company’s Performance Stock Units, or PSUs and related information:

	PSUs Outstanding
	Number of Shares			Weighted- Average Grant Date Fair Value
Unvested — December 31, 2022		209,230		$	98.09
PSUs granted		362,470			50.29
PSUs vested		(27,581	)		141.86
PSUs cancelled		(38,013	)		106.80
Unvested — December 31, 2023		506,106			60.82

The fair value of the PSUs is determined on the grant date based on the fair value of the Company’s common stock, except for certain PSUs with a market vesting condition, for which fair value is estimated using a Monte Carlo simulation model. PSUs are subject to vest only if certain specified criteria are achieved and the employees’ continued service with the Company. For certain PSUs, the number of PSUs that may vest are also subject to the achievement of certain specified criteria, including both performance conditions and market conditions. As of December 31, 2023, certain specified criteria were deemed probable of achievement or already achieved. Stock-based compensation for PSUs is recognized over the service period beginning in the period the Company determines it is probable that the performance criteria will be achieved. The total grant date fair value of the PSUs vested during the years ended December 31, 2023, 2022, and 2021 was $3.9 million, $1.6 million, and $9.2 million, respectively, with an aggregate intrinsic value of the shares of $1.3 million, $2.0 million and $18.9 million, respectively.

Employee Stock Purchase Plan

In January 2014, the Company adopted the 2014 Employee Stock Purchase Plan, or ESPP, which was amended and restated in June 2023. Under the ESPP, eligible employees may purchase common stock at 85% of the lesser of the fair market value of common stock on the offering date or the purchase date with a six-month look-back feature. ESPP purchases are settled with common stock from the ESPP’s previously authorized and available pool of shares. During the year ended December 31, 2023, the Company issued 195,462 shares of common stock under the ESPP. As of December 31, 2023, an aggregate of 6,609,795 shares of common stock have been authorized for future issuance on the ESPP.

Stock-Based Compensation Expense

Total stock-based compensation recognized was as follows (in thousands):

	Year Ended December 31,
	2023		2022		2021
Cost of sales	$	1,166	$	902	$	871
Research and development		74,531		74,464		59,097
Selling, general and administrative		59,516		55,002		45,011
Total stock-based compensation expense	$	135,213	$	130,368	$	104,979

Stock-based compensation of $1.9 million, $2.2 million, and $1.7 million was capitalized into inventory for the years ended December 31, 2023, 2022, and 2021, respectively. Capitalized stock-based compensation is recognized as cost of sales when the related product is sold. As of December 31, 2023, the total unrecognized compensation expense related to unvested equity awards, net of estimated forfeitures, was $219.8 million, which the Company expects to recognize over an estimated weighted-average period of 2.2 years. In determining the estimated fair value of the stock options, PSOs and ESPP, the Company uses the Black-Scholes option-pricing model and assumptions discussed below. Each of these inputs is subjective and generally requires significant judgment to determine.

Expected Term—The Company’s expected term represents the period that the Company’s stock-based awards are expected to be outstanding and is determined using the simplified method (based on the mid-point between the vesting date and the end of the contractual term).

Expected Volatility—The Company’s expected volatility is based on historical volatility over the look-back period corresponding to the expected term.

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ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

Risk-Free Interest Rate—The risk-free interest rate is based on the U.S. Treasury zero coupon issues in effect at the time of grant for periods corresponding with the expected term of option.

Expected Dividend—The Company has never paid dividends on its common stock and has no plans to pay dividends on its common stock. Therefore, the Company used an expected dividend yield of zero.

Strike price for options awards and PSOs is equal to the closing market value of our common stock on the date of grant.

The fair value of stock option awards granted was estimated at the date of grant using a Black-Scholes option-pricing model with the following weighted-average assumptions:

	Year Ended December 31,
	2023	2022	2021
Expected term (years)	6.07	6.07	6.06
Expected volatility	55%	56%	60%
Risk-free interest rate	4.2%	2.0%	1.0%
Expected dividend rate	0.0%	0.0%	0.0%

The fair value of PSOs granted was estimated at the date of grant using a Black-Scholes option-pricing model with the following weighted-average assumptions:

	Year Ended December 31,
	2022
Expected term in years	3.60
Expected volatility	57%
Risk-free interest rate	1.5%
Expected dividend rate	0.0%

13.Defined Contribution Plan

The Company sponsors a retirement plan in which substantially all of its full-time employees in the U.S. and certain other foreign countries are eligible to participate. Eligible participants may contribute a percentage of their annual compensation to this plan, subject to statutory limitations. The Company recorded $9.7 million, $9.0 million, and $5.5 million as expense related to the plan for the years ended December 31, 2023, 2022, and 2021, respectively.

14.Income Taxes

The components of the Company’s loss before income taxes were as follows (in thousands):

	Year Ended December 31,
	2023		2022			2021
Domestic	$	608,166	$	703,411		$	455,314
Foreign		298		(1,686	)		(2,333	)
Total loss before income taxes	$	608,464	$	701,725		$	452,981

F-33

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

The components of the Company’s income tax provision were as follows (in thousands):

	Year Ended December 31,
	2023			2022			2021
Current provision for income taxes:
Federal	$	—		$	—		$	—
State		(3,187	)		6,062			(14	)
International		3,127			1,274			1,058
Total current tax provision		(60	)		7,336			1,044
Deferred tax provision:
Federal		—			—			—
State		(1,608	)		(1,640	)		—
International		(157	)		—			—
Total deferred tax provision		(1,765	)		(1,640	)		—
Total (benefit from) provision for income taxes	$	(1,825	)	$	5,696		$	1,044

The Company has incurred net operating losses since inception. The Company has not reflected any benefit of such net operating loss carryforwards in the accompanying financial statements. The Company has established a full valuation allowance against its deferred tax assets due to the uncertainty surrounding the realization of such assets.

Beginning in 2022, the Tax Cuts and Jobs Act of 2017 eliminated the right to deduct research and development expenditures for tax purposes in the period the expenses were incurred and instead requires all U.S. and foreign research and development expenditures to be amortized over five and fifteen tax years, respectively. Due to this required capitalization of research and development expenditures and the significant taxable income generated as a result of our sale of royalties in July 2022, the Company has recorded current state income tax expense of $6.1 million for the year ended December 31, 2022. For the year ended December 31, 2023, the Company recognized an income tax benefit of $4.8 million attributable to modifications in its state apportionment methodology. The Company realized no benefit for current year losses due to a full valuation allowance against the U.S. net deferred tax assets. The benefit was offset by an income tax expense of $3.0 million from foreign jurisdictions.

The effective tax rate of our provision for income taxes differs from the federal statutory rate as follows:

	Year Ended December 31,
	2023				2022				2021
Federal statutory income tax rate		21.0		%		21.0		%		21.0		%
State income taxes, net of federal benefit		0.8				(0.4	)			—
Federal tax credits		7.3				5.9				7.2
Other		(0.7	)			(0.1	)			0.5
Nondeductible permanent items		(0.3	)			(0.6	)			(0.8	)
Stock-based compensation		(1.8	)			(1.2	)			1.3
Uncertain tax positions		(1.4	)			(1.2	)			(1.4	)
Change in valuation allowance		(24.1	)			(24.0	)			(27.9	)
Foreign rate differential		(0.5	)			(0.2	)			(0.1	)
Provision for income taxes		0.3		%		(0.8	)	%		(0.2	)	%

F-34

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

The tax effect of temporary differences that give rise to significant portions of the deferred tax assets is presented below (in thousands):

	Year Ended December 31,
	2023			2022
Deferred tax assets:
Loss carryforwards	$	266,253		$	231,835
Tax credits		305,198			260,546
Stock options		44,795			39,784
Accruals and reserves		27,694			27,029
Fixed assets and intangibles		33,853			39,233
Liabilities for sales of future royalties		205,400			214,900
Basis difference in equity investments		8,423			8,971
Capitalized research and development costs		149,898			75,335
Other		281			3,028
Gross deferred tax assets		1,041,795			900,661
Valuation allowance		(1,035,836	)		(894,518	)
Total deferred tax assets		5,959			6,143
Deferred tax liabilities:
In-process research and development		(30,688	)		(31,667	)
Right-of-use lease assets		(5,329	)		(6,143	)
Gross deferred tax liabilities		(36,017	)		(37,810	)
Net deferred tax liabilities	$	(30,058	)	$	(31,667	)

As of December 31, 2023 and 2022, the Company had approximately $1,004.8 million and $756.6 million, respectively, of federal net operating loss carryforwards available to reduce future taxable income that will begin to expire in 2031. As of December 31, 2023 and 2022, the Company had approximately $659.9 million and $710.0 million, respectively, of state net operating loss carryforwards available to reduce future taxable income that will begin to expire in 2031.

As of December 31, 2023 and 2022, the Company had federal research tax credit carryforwards of approximately $46.9 million and $32.6 million, respectively, available to reduce future tax liabilities that will begin to expire in 2030. As of December 31, 2023 and 2022, the Company had state research credit carryforwards of $74.4 million and $59.9 million, respectively, available to reduce future tax liabilities that will be carried forward indefinitely.

As of December 31, 2023 and 2022, the Company had federal Orphan Drug Credits of $269.6 million and $239.3 million, respectively, available to reduce future tax liabilities that will begin to expire in 2031.

The Company’s ability to use net operating loss and tax credit carryforwards to reduce future taxable income and liabilities may be subject to annual limitations pursuant to Internal Revenue Code Sections 382 and 383 as a result of ownership changes in the past and future. As a result of ownership changes in 2012 and 2011, $3.6 million of federal net operating loss carryforwards, $3.6 million of state net operating loss carryforwards, and $0.2 million of federal tax credits are permanently limited. Deferred tax assets for net operating losses and tax credits have been reduced and a corresponding adjustment to the valuation allowance has been recorded.

The valuation allowance increased by $141.3 million and $193.8 million during the years ended December 31, 2023 and 2022, respectively.

Due to a change in the state tax rates, the Company recorded a net decrease to the deferred tax liability of $1.6 million with a corresponding deferred income tax benefit of $1.6 million for the year ended December 31, 2023.

F-35

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

The Company recorded unrecognized tax benefits for uncertainties in income taxes. A reconciliation of the Company’s unrecognized tax benefits follows (in thousands):

	December 31,
	2023		2022			2021
Balance at beginning of year	$	66,794	$	55,360		$	46,662
Additions based on tax positions related to current    year		12,562		11,316			8,542
Additions for tax positions of prior years		642		377			356
Reductions for tax positions of prior years		—		(259	)		(200	)
Balance at end of year	$	79,998	$	66,794		$	55,360

Approximately $1.3 million in unrecognized tax benefits would impact the Company’s effective tax rate if recognized. The Company has elected to include interest and penalties as a component of tax expense. For the year ended December 31, 2023, the Company recognized accrued interest and penalties of $0.2 million as a component of income tax expense. No accrued interest and penalties were recognized as a component of income tax expense during the years ended December 31, 2022 and 2021. The Company does not anticipate that the amount of existing unrecognized tax benefits will significantly increase or decrease during the next year.

It is the Company’s intention to reinvest the earnings of its non-U.S. subsidiaries in their operations. As of December 31, 2023, the Company had not made a provision for any incremental foreign withholding taxes on approximately $10.8 million of the excess of the amount of net income for financial reporting over the tax basis of investments in foreign subsidiaries that are essentially permanent in duration. If these earnings were repatriated to the U.S., the deferred tax liability associated with these temporary differences would result in a nominal amount of withholding taxes.

The Company files income tax returns in the U.S. federal, 40 state tax jurisdictions, and ten foreign countries. The federal and state income tax returns from inception to December 31, 2023 remain subject to examination.

15.Commitments and Contingencies

The Company has various manufacturing, construction, clinical, research, and other contracts with vendors in the conduct of the normal course of its business. Other than as noted below, contracts are terminable, with varying provisions regarding termination. If a contract with a specific vendor were to be terminated, the Company would only be obligated for the products or services that the Company had received at the time the termination became effective.

Manufacturing and service contract obligations primarily relate to the manufacture of inventory for our approved products, the majority of which are due in the next 12 months.

As of December 31, 2023, the aggregate payments under contractually-binding manufacturing and service agreements are as follows (in thousands):

	Year Ended December 31,
	2024		2025		Total
Manufacturing and Services	$	27,899	$	5,718	$	33,617

The terms of certain of the Company’s licenses, royalties, development and collaboration agreements, as well as other research and development activities, require the Company to pay potential future milestone payments based on product development success. The amount and timing of such obligations are unknown or uncertain. These potential obligations are further described in “Note 8. License and Research Agreements.”

See “Note 9. Leases” for lease commitments.

Contingencies

While there are no material legal proceedings the Company is aware of, the Company may become party to various claims and complaints arising in the ordinary course of business. Management does not believe that any ultimate liability resulting from any of these potential claims will have a material adverse effect on its results of operations, financial position, or liquidity. However, management cannot give any assurance regarding the ultimate outcome of these claims, and their resolution could be material to operating results for any particular period, depending upon the level of income for the period.

F-36

ULTRAGENYX PHARMACEUTICAL INC.

Notes to Consolidated Financial Statements (continued)

Guarantees and Indemnifications

The Company indemnifies each of its directors and officers for certain events or occurrences, subject to certain limits, while the director or officer is or was serving at the Company’s request in such capacity, as permitted under Delaware law and in accordance with its certificate of incorporation and bylaws. The term of the indemnification period lasts as long as a director or officer may be subject to any proceeding arising out of acts or omissions of such director and officer in such capacity. The maximum amount of potential future indemnification is unlimited; however, the Company currently holds director liability insurance. This insurance allows the transfer of risk associated with the Company’s exposure and may enable it to recover a portion of any future amounts paid. The Company believes that the fair value of these indemnification obligations is minimal. Accordingly, it has not recognized any liabilities relating to these obligations for any period presented.

16.Related Party Transaction

In July 2022, the Company entered into an agreement with a non-profit foundation in which two members of the Company’s board of directors, including the Company’s Chief Executive Officer, also serve as board members of the foundation, whereby an aggregate $1.0 million contribution is being paid to the foundation over a four-year period, beginning in the third quarter of 2022, to support rare disease education and awareness. As a result, the Company recorded $0.3 million and $0.3 million as research and development expense for this agreement for the years ended December 31, 2023 and 2022, respectively.

17.Net Loss per Share

The following table sets forth the computation of the basic and diluted net loss per share during the years ended December 31, 2023, 2022, and 2021 (in thousands, except share and per share data):

	Year Ended December 31,
	2023			2022			2021
Numerator:
Net loss	$	(606,639	)	$	(707,421	)	$	(454,025	)
Denominator:
Weighted-average shares used to compute net loss per    share, basic and diluted		73,543,862			69,914,225			67,795,540
Net loss per share, basic and diluted	$	(8.25	)	$	(10.12	)	$	(6.70	)

The following weighted-average outstanding common stock equivalents were excluded from the computation of diluted net loss per share for the periods presented because including them would have been antidilutive:

	Year Ended December 31,
	2023		2022		2021
Options to purchase common stock,     restricted stock units, and performance stock units		14,152,286		11,290,935		8,214,063
Employee stock purchase plan		8,450		7,581		3,511
		14,160,736		11,298,516		8,217,574

18.Accumulated Other Comprehensive Income (Loss)

Total accumulated other comprehensive income (loss) consisted of the following (in thousands):

	Year Ended December 31,
	2023			2022
Cumulative foreign currency translation adjustment	$	(606	)	$	(845	)
Unrealized gain (loss) on securities available-for-sale		1,253			(5,728	)
Total accumulated other comprehensive income (loss)	$	647		$	(6,573	)

F-37

EX-10.18

Exhibit 10.18

[***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE THE INFORMATION (I) IS NOT MATERIAL AND (II) THE TYPE THAT THE REGISTRANT TREATS A PRIVATE OR CONFIDENTIAL.

Commercial Supply Agreement

Triheptanoin Ultrapure

Between

Ultragenyx Pharmaceutical Inc.

60 Leveroni Court Novato, CA 94949 USA

(Herein known as UGX)

And

IOI Oleo GmbH Herrengraben 31

20459 Hamburg, Germany (Herein known as IOI)

Hereinafter referred to individually as a “Party” and together as the “Parties”

1

Preamble

Whereas, UGX is a company engaged in the pharmaceutical field focusing on development of rare disease therapies and has obtained regulatory approval to market certain medicinal products based on active pharmaceutical ingredients;

Whereas, IOI is a supplier of oleochemical specialties for a large number of pharmaceutical and industrial applications, including the development and manufacturing of drug substance.

Whereas, given IOI’s know-how, expertise, capability, experience and infrastructure, Ultragenyx entrusted IOI with, and IOI accepted, the manufacturing, packing, releasing of Ultragenyx’s Triheptanoin Ultrapure Drug Substance (the PRODUCT) in accordance with the terms and conditions of the Supply Agreement between CREMER OLEO GmbH & Co KG as legal predecessor of IOI and Ultragenyx Pharmaceutical Inc. of November 19th 2012 (“INITIAL AGREEMENT”);

Whereas, as the PARTIES have determined the INITIAL AGREEMENT to be terminated and replaced with a modified agreement to better regulate their collaboration in particular, but not limited to, the evolving regulatory status of PRODUCT across the world, both PARTIES have expressed their intention to better regulate respective duties and obligations in relation to the manufacturing of Ultragenyx’s Triheptanoin Ultrapure Drug Substance;

Whereas, each Party herewith expresses once again its commitment to (i) work in a partnership model, (ii) always apply the appropriate level of trust and transparency, (iii) respect a duty of good faith and fair dealing in connection with its performance under this AGREEMENT, (iv) perform its obligations under this AGREEMENT in a diligent, legal, ethical and professional manner so as to advance the purposes and intent of this AGREEMENT.

Now, Therefore, in consideration of the mutual agreements and covenants contained herein, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties, intending to be legally bound, hereby agree as follows:

2

Contents

1. DEFINITION	5
2. SCOPE OF THE AGREEMENT	7
3. IOI`S RESPONSIBILITIES	8
4. UGX RESPONSIBILITIES	9
5. GOVERNANCE MODEL	9
6. RECORDS, AUDITS AND INSPECTIONS	11
7. INTELLECTUAL PROPERTY	10
8. DEFECTIVE PRODUCT	12
9. INDEMNIFICATION FOR THIRD-PARTY CLAIMS	13
10. LIMITATION OF LIABILITIES	14
11. INSURANCE	15
12. FORCE MAJEURE	15
13. TERM AND TERMINATION	15
14. MISCELLANEOUS	15
APPENDIX I (COMMERCIAL TERMS)	20
APPENDIX II (COMPLIANCE)	23
APPENDIX III (PRICES AND FEES)	25
APPENDIX IV (QUALITY AND TECHNICAL AGREEMENT)	19

3

APPENDIX V (PRODUCT SPECIFICATION)	22
APPENDIX VI (RAW MATERIAL SPECIFICATIONS)	24
APPENDIX VII (CDA)	29
APPENDIX VIII (THIRD PARTY LABORATORIES)	30

4

1.Definitions

AGREEMENT means this Commercial Supply AGREEMENT.

ADDITIONAL SERVICE means any service provided by IOI and agreed by both PARTIES, except all activities involved in MANUFACTURE and TECHNICAL RELEASES of PRODUCT. Additional services are subject to individual OFFERS. They are defined in Appendix I.

AFFILIATE shall mean with respect to a Party, any person, corporation, company, partnership or other entity that controls, is controlled by, or is under common control with that Party. For the purpose of this definition, “control” shall mean direct ownership of fifty percent (50%) or more of the shares of stock entitled to vote for the election of directors, in the case of a corporation, or fifty percent (50%) or more of the equity interest in the case of any other type of legal entity, status as a general partner in any partnership, or any other arrangement whereby the entity or person controls or has the right to control the board of directors or equivalent governing body of a corporation or other entity, or the ability to cause the direction of the management or policies of a corporation or other entity.

BUSINESS DAY shall mean each day of the week on which a Party`s offices are open for business (usually any day except Saturday, Sunday and legal holidays).

CALENDAR QUARTER shall mean the respective periods of 3 (three) consecutive CALENDAR MONTHs ending March 31st, June 30th, September 30th and December 31st.

CALENDAR MONTH shall mean any of the 12 (twelve) CALENDAR MONTHs of a CALENDAR YEAR.

CALENDAR YEAR shall mean a period of 12 (twelve) consecutive months corresponding to a calendar year commencing on the first days of January.

CONFIDENTIAL INFORMATION shall have the meaning as provided in Appendix 7.

DELIVERY DATE means the point in time set out in the confirmed FORECAST at which PRODUCT is delivered to UGX under the applicable Incoterm®.

EQUIPMENT means any equipment system to support the manufacturing and/or packaging of UGX`s PRODUCT.

EXECUTIVE LEADERSHIP shall mean for the purpose of this AGREEMENT the [***] of UGX and the [***] of IOI respectively (or whoever is on these roles ad interim).

FACILITY shall mean the IOI manufacturing site located in [***] adequate to MANUFACTURE the PRODUCT by means of validated processing equipment and manufacturing processes for the PRODUCT, trained and competent personnel with relevant knowledge and experience.

FINAL RELEASE shall mean PRODUCT quality release by UGX or UGX`s delegate as per QTA.

5

FORCE MAJEURE shall have the meaning as provided in Section 12.

FORECAST shall have the meaning as provided in Appendix I.

cGMP means those practices related to the manufacture of medicinal products for human use laid down in international guidelines and regulations such as the GMP rules of the World Health Organization, the United States Code of Federal Regulations (Title 21, Parts 210), and the European Union Guide to Good Manufacturing Practice (Eudralex Volume 4). Current Good Manufacturing Practice (cGMP) is the applicable term in the United States. For the purpose of this AGREEMENT, the terms GMP and cGMP are equivalent.

HIDDEN DEFECT means a defect of PRODUCT already present at the time of delivery but not detectable at the time of the inspection.

IMPROVEMENT means technical and business process optimization that is beneficial for the manufacturing process, product quality, financial aspect or supply of PRODUCT.

INTELLECTUAL PROPERTY RIGHTS or IP RIGHTS means rights in or arising from patents, patent applications (including all utility and design patents and patent applications), inventions, trademarks, service marks, trade names, internet domain names, rights in designs, rights in get-up and trade dress, goodwill and the right to sue for passing off or unfair competition, copyrights, (including all computer applications, programs and other software, including without limitation operating software, network software, firmware, middleware, and design software rights in computer software and databases), database rights, industrial property rights, moral rights of authors, rights to use and protect the confidentiality of, confidential information (including know-how and trade secrets), utility models, any common law rights arising from use of the foregoing, all rights of use, renewal, continuations, divisions, extensions and the like relating to the foregoing, and other intellectual property rights, in each case whether registered or unregistered and including any applications and rights to apply for the grant of any such rights and all rights and forms of protection having an equivalent or similar effect anywhere in the world.

JOINT WORKING TEAM shall mean the team selected by the STEERING COMMITTEE in accordance with the criteria set out under Section 5 of this AGREEMENT.

MANUFACTURE or MANUFACTURING means compounding, filling and processing, production, testing and packaging of material by IOI to obtain PRODUCT in accordance with the SPECIFICATION under cGMP conditions.

MATERIAL CHANGE IN CONTROL or BUSINESS MODEL shall mean any of the following: (i) the sale or disposition of all or substantially all of the assets of a Party to a THIRD-PARTY, (ii) the acquisition by a THIRD-PARTY, of more than 50% of a Party’s outstanding shares of voting capital stock (e.g. capital stock entitled to vote generally for the election of directors), or (iii) the merger or consolidation of a Party with or into another corporation. References in this definition to a THIRD-PARTY shall exclude AFFILIATES.

OFFER shall mean IOI`s quotation containing the details of the proposed ADDITIONAL SERVICES subject to UGX`s binding order.

6

ON-TIME DELIVERY shall mean PRODUCT released by both Parties and ready to be picked up under the applicable INCOTERM® in accordance with the applicable FORECAST.

PRODUCT shall mean Triheptanoin Ultrapure, a Drug Substance as specified in Appendix 5 to this agreement and solely used in pharmaceutical applications.

PURCHASE ORDER shall mean a firm order placed and issued by UGX with a corresponding PURCHASE ORDER number to IOI reflecting forecasted DELIVERY DATE within the binding forecast period.

QUALITY AND TECHNICAL AGREEMENT (QTA) shall be drafted substantially in the same form as Appendix IV.

QUARANTINE SHIPMENT means a shipment of PRODUCT before the quality release by IOI in accordance with the QTA.

SERVICES means all activities related to MANUFACTURING of PRODUCT as described in this AGREEMENT and includes all activities involved in MANUFACTURING of PRODUCT and according to the quality standards set forth in the QTA including costs of in-process control, quality assurance, Continuous Process Verification, Product Quality Review, quality control and release, storage of raw materials, sharing raw analytical/process data, providing relevant documentation and THIRD-PARTY MATERIAL procured by IOI, disposal of waste.

SPECIFICATION means the PRODUCT specification [***], as amended from time to time by mutual agreement between the Parties, and as defined in IOI’s quality system attached as Appendix V to this AGREEMENT and THIRD PARTY MATERIAL specifications for [***] as defined in Appendix VI.

STEERING COMMITTEE shall mean the committee selected by the Parties in accordance with the criteria set out under Section 5 of this AGREEMENT.

TECHNICAL RELEASE shall mean the release of PRODUCT by IOI and UGX in accordance with the QTA.

THIRD-PARTY means any person other than UGX, IOI and their respective AFFILIATES.

THIRD-PARTY MATERIAL means all material procured by IOI for the MANUFACTURING of the PRODUCT.

2.Scope of the AGREEMENT

2.1.UGX hereby retains IOI to MANUFACTURE and supply PRODUCT as well as perform SERVICES and ADDITIONAL SERVICES to and for the benefit of UGX in accordance with the terms of this AGREEMENT and the applicable SPECIFICATIONS and applicable QTA. On the term set forth herein, UGX will purchase and pay PRODUCT from IOI and pay ADDITIONAL SERVICES fees as detailed under this AGREEMENT.

2.2.Quality control testing and analysis of any batch of PRODUCT MANUFACTURED by IOI shall be conducted by IOI and / or THIRD-PARTY labs as stipulated in Appendix VIII. Any different setting regarding where to perform Quality Control testing and analysis of any batch of PRODUCT MANUFACTURED by IOI, for example quality control testing and analysis by a THIRD-PARTY independent laboratory engaged by UGX,

7

shall be discussed and agreed in good faith by the PARTIES. It is understood by the PARTIES that: (i) [***] shall be [***] by UGX to [***], provided IOI’s [***]are [***] to [***]; and (ii) in no event [***].

2.3.IOI undertakes to refrain from performing any manufacturing services of the PRODUCT for any party other than Ultragenyx, [***].

UGX shall purchase the PRODUCT exclusively from IOI.

2.4.Attached to this AGREEMENT are the following Appendixes which form an integral part of this AGREEMENT:

Appendix I	Commercial Terms
Appendix II	Compliance
Appendix III	Prices and Fees
Appendix IV	QUALITY AND TECHNICAL AGREEMENT (QTA)
Appendix V	PRODUCT SPECIFICATION
Appndix VI	RAW MATERIAL SPECIFICATIONS
Appendix VII	CDA
Appendix VIII	THIRD-PARTY laboratories

2.5.In case of any inconsistencies between this AGREEMENT, the Appendices and/or an OFFER referring to it, the Appendices and/or the OFFER shall prevail. However, if there is any contradiction or inconsitency between this AGREEMENT and the QTA, then this AGREEMENT will take precedence.

2.6.This AGREEMENT, including all its Appendixes constitutes the entire understanding between the Parties as of the EFFECTIVE DATE with respect to the subject matter hereof and supersedes all prior agreements (including the INITIAL AGREEMENT), negotiations, understandings, representations, statements and writings relating thereto.

2.7.Neither Party shall alter or adjust this AGREEMENT or any Appendixes to it without the prior written permission of the other Party.

3.IOI`s Responsibilities

3.1.IOI shall comply with this AGREEMENT, all its Appendixes (including but not limited to Appendix IV) and cGMP.

8

3.2.IOI shall render the SERVICES, the ADDITIONAL SERVICES and MANUFACTURE the PRODUCT in the FACILITY unless differently agreed to by the Parties in writing.

3.3.All the responsibilities and obligations listed under Sections 3.1 and 3.2. will be covered by IOI at their [***]. In case IOI incurs costs in connection with the [***].

3.4.IOI will notify UGX immediately but not later than within [***] BUSINESS DAYS after becoming aware of any potential failure to deliver the PRODUCT within the timelines agreed in each applicable FORECAST.

3.5.IOI will provide UGX an inventory report upon request.

3.6.IOI will undertake [***] to implement and operate an effective system for protecting MANUFACTURE and supply of PRODUCT against risks related to cyber-crime incidents.

4.UGX Responsibilities

4.1UGX shall purchase and pay the quantity of PRODUCT set out in the BINDING PERIOD of the FORECAST, as specified in Appendix I.

4.2UGX shall be responsible to provide IOI with complete and accurate information to enable IOI to MANUFACTURE the PRODUCT.

4.3UGX shall comply with Appendices I and II.

4.4UGX shall provide reasonable assistance to IOI in dealing with regulatory changes related to the PRODUCT, SERVICES or ADDITIONAL SERVICES.

5.Governance Model

5.1.The partnership model includes a STEERING COMMITTEE and a JOINT WORKING TEAM focusing on operational execution. The JOINT WORKING TEAM will be led by a project/relationship manager of each Party (Joint Working Team Leads).

5.2.The Parties shall establish a STEERING COMMITTEE consisting of [***] individuals. Each Party will nominate [***] STEERING COMMITTEE members.

5.3.Either Party may replace its STEERING COMMITTEE members by written notice to the other Party.

5.4.The purpose of the STEERING COMMITTEE is to:

a)establish and maintain an effective and efficient collaboration between the Parties:

9

b)confirm the Joint Working Team Leads by each Party;

c)oversee the JOINT WORKING TEAM`s performance in business review meetings;

a)evaluate in good faith and ratify any technical, business process and/or quality improvements proposed by the JOINT WORKING TEAMS;

b)act as escalation body for issue resolution;

c)define the framework for continuous improvement, mutual long-term objectives and priorities;

d)any other topics assigned to it in compliance with this AGREEMENT or following the mutual decision of the Parties.

5.5.The Parties shall establish a JOINT WORKING TEAM, consisting of at least [***] of each Party in the [***] and [***] of each Party in [***]. Thus, the minimum size of the JOINT WORKING TEAM shall be [***] members.

5.6.Either Party may replace its JOINT WORKING TEAM leads and members by notice to the other Party.

5.7.The purpose of the JOINT WORKING TEAM is to:

a)drive and improve performance of MANUFACTURE, SERVICES and ADDITIONAL SERVICES, if any, and the JOINT WORKING TEAM functionality;

b)establish, manage and review routinely other relevant key performance indicators applicable to MANUFACTURING, SERVICES and ADDITIONAL SERVICES;

c)manage MANUFACTURING, SERVICES and ADDITIONAL SERVICES risks, including lead times and safety stock management of PURCHASED MATERIALS;

d)overseeing and monitoring MANUFACTURING and manage any and all issues related to MANUFACTURING, SERVICES and ADDITIONAL SERVICES;

e)facilitate expeditious resolution of any issues, also in accordance with the instructions from the JOINT STEERING COMMITTEE, if received;

f)maintain a collaborative and constructive relationship at operational level;

g)potentially propose any IMPROVEMENT to the STEERING COMMITTEE.

5.8.The JOINT WORKING TEAM shall conduct its discussion in good faith with a view to operating to the mutual benefit of the Parties.

5.9.In addition to any other topics to be discussed in the agenda of the relevant meeting, the following matters shall be considered to be discussed during the JOINT WORKING TEAM meetings:

a)team member updates;

b)performance review (services, quality, relationship, financials);

c)risk evaluation and associated risk mitigation projects;

d)review the status of past meeting action items.

6.Records, Audits and Inspections

6.1At [***], IOI will create and maintain accurate and relevant records related to MANUFACTURING, SERVICES and ADDITIONAL SERVICES, limited to [***] (collectively, the “RECORDS”). The Parties will [***] of

10

the RECORDS, to the extent they are [***] and do not [***]. In such a circumstance, each Party will [***] on the RECORDS containing [***].

6.2All original RECORDS of the development and MANUFACTURE of PRODUCT hereunder will be retained and archived by IOI for a period set in accordance with cGMP, APPLICABLE LAW and the QTA (the “RETENTION PERIOD”). In case of conflict between the mentioned sources, the QTA shall prevail. Following the RETENTION PERIOD, IOI will not destroy any UGX PROPRIETARY RECORDS or JOINTLY OWNED RECORDS without first giving UGX written notice and the opportunity to return the UGX PROPRIETARY RECORDS or JOINTLY OWNED RECORDS [***].

6.3Upon request, IOI agrees to share with UGX [***], which ascertains the accuracy of IOI’s annual balance sheet, as well as the key financial data supporting IOI’s independent auditor’s report, provided that UGX shall keep [***] strictly confidential with the prohibition of disclosure it to any third party without IOI’s prior written consent.

6.4UGX has the right to audit and inspect the FACILITY, equipment, materials and RECORDS as required by cGMP guidelines, this AGREEMENT and the QTA.

6.5Not more frequently than [***] per [***], upon [***] advance written notice and subject to compliance with all applicable confidentiality provisions herein, UGX may request to perform cGMP audits at the FACILITY and IOI shall permit for such audits as outlined in the QTA. UGX and its duly authorized representatives may have access together with a IOI employee to the FACILITY, during operational hours and during active MANUFACTURING, to enter and inspect any premises and MANUFACTURING SERVICES and/or ADDITIONAL SERVICES to ascertain compliance by IOI with the terms of this AGREEMENT. IOI will cooperate with UGX to facilitate the evaluation and inspection, and provide reasonable assistance to UGX. UGX will reasonably cooperate with IOI to mitigate disruption to IOI’s operations. Scope and further details are set forth in the QTA attached to Appendix III of this AGREEMENT. It is understood by the Parties that upon prior written approval by IOI UGX may be accompanied by or delegate to THIRD PARTY’s representatives the performance of such cGMP audits; provided that such THIRD PARTY’s representatives shall (i) be bound by confidentiality obligations toward IOI no less stringent than those identified in this AGREEMENT and (ii) finalize a three-way confidentiality AGREEMENT which shall be accepted by all contracting parties.

6.6UGX and/or its designees may perform for-cause audits as outlined in the QTA. IOI shall make the FACILITY and the relevant personnel involved in the performance of MANUFACTURING, SERVICES and ADDITIONAL SERVICES under this AGREEMENT available, within reasonable business hours, and advanced written notice ([***]) for the purpose of any UGX audits.

6.7IOI shall [***] inform UGX of any inspections by competent regulatory authorities at the FACILITY which affects the MANUFACTURE of PRODUCT under this AGREEMENT, within the terms provided in the QTA. In the event that the inspection reveals that IOI is not in compliance with the APPLICABLE LAWS and applicable regulatory regulations, including cGMP, and receives written observations (or any other written communication) by such REGULATORY AUTHORITY which involve the PRODUCT, IOI shall (i) use its best efforts to cure such non-compliance within the timing required by the REGULATORY AUTHORITY, (ii)

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inform UGX of any proposed written response by IOI to any such REGULATORY AUTHORITY as far as it relates to MANUFACTURE of PRODUCT and (iii) provide UGX with copies of all documentation as far as it relates to MANUFACTURE of PRODUCT within the terms provided in the QTA. UGX will have the opportunity to review and provide input to the response to IOI as promptly as practicable and in accordance with the QTA.

6.8IOI agrees that for a justified and documented reason, and only after prior written approval from IOI , which should not be unreasonably denied by IOI up to [***] PERSONS of UGX may be present at the FACILITY during the MANUFACTURING for the purpose of [***]. Any PERSON IN PLANT who are present at the FACILITY, shall comply with IOI’s site regulations, SOPs and rules.

7.Intellectual Property

7.1.Neither Party shall, as a result of this AGREEMENT, acquire any right, title, or interest in any INTELLECTUAL PROPERTY RIGHTS that the other Party owns or controls as of the EFFECTIVE DATE of this AGREEMENT, or that the other Party obtains ownership or control of separately and apart from the MANUFACTURING or performance of the SERVICES under this AGREEMENT (“BACKGROUND INTELLECTUAL PROPERTY”).

7.2.UGX shall own exclusively all rights, titles, and interests in any and all inventions, discoveries and INTELLECTUAL PROPERTY RIGHTS that IOI may conceive, invent, reduce to practice, develop or make, solely or jointly with UGX in the performance of the SERVICES and/or ADDITIONAL SERVICES directly related to the PRODUCT or UGX's BACKGROUND INTELLECTUAL PROPERTY (collectively, “UGX INTELLECTUAL PROPERTY”). IOI hereby assigns, and commits to assign and have assigned, to UGX all UGX INTELLECTUAL PROPERTY. In turn and always subject to the confidentiality terms outlined in this Agreement, UGX commits to grant to IOI during the Term (as herein defined) the exclusive, free-of- charge, worldwide right and licence to practice, use, execute, reproduce, display, modify and exploit in any manner whatsoever such UGX INTELLECTUAL PROPERTY [***]. For clarity’s sake, it is understood by the Parties that IOI's rights under this Section 7.2. shall not include the right to grant sub licences to any persons, for any territories and on any terms.

7.3.Notwithstanding the foregoing, IOI shall own all rights, titles and interests in any inventions, discoveries and INTELLECTUAL PROPERTY RIGHTS that IOI may develop, conceive, invent, reduce to practice or make in the course of MANUFACTURING of PRODUCT or performance of the SERVICES and/or ADDITIONAL SERVICES that is an improvement of or modification to the MANUFACTURE OF PRODUCT or IOI’s BACKGROUND INTELLECTUAL PROPERTY (collectively, “IOI INTELLECTUAL PROPERTY”).

7.4.IOI commits to promptly inform UGX according to Section 14.3 of any violation of UGX BACKGROUND INTELLECTUAL PROPERTY and/or UGX INTELLECTUAL PROPERTY and further agrees, [***], to (i) assist UGX or its designee(s) under APPLICABLE LAWS, in obtaining, maintaining, defending and enforcing patents and all other instruments in nature of patents with respect to any UGX BACKGROUND INTELLECTUAL PROPERTY and/or UGX INTELLECTUAL PROPERTY, (ii) provide such information and assistance and execute such document as UGX or its designee(s) may request from time to time, and (iii) confirm the assignments hereunder. For clarity, IOI agrees that UGX or its designee(s) shall be the only Party responsible for filing, prosecuting and maintaining any patent application covering UGX BACKGROUND INTELLECTUAL PROPERTY and/or UGX INTELLECTUAL PROPERTY.

7.5.If the MANUFACTURING of PRODUCT and/or performance of the SERVICES and/or ADDITIONAL

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SERVICES requires the use of IOI BACKGROUND INTELLECTUAL PROPERTY, IOI hereby grants to UGX the necessary rights of using IOI BACKGROUND INTELLECTUAL PROPERTY rights solely for the marketing, distribution and sale of PRODUCT. Such license is granted for PRODUCT manufactured during the term of this AGREEMENT on a worldwide basis, non-exclusively and royalty-free, unless expressly agreed otherwise. Such rights shall be sublicensable by UGX to its AFFILIATES, licensees, collaboration partners or other parties who receive a license(s) or sublicense(s) to UGX BACKGROUND INTELLECTUAL PROPERTY or UGX INTELLECTUAL PROPERTY from UGX.

7.6.If the performance of this AGREEMENT requires the use of IP RIGHTS of UGX or of THIRD-PARTIES, UGX hereby grants to or procures for IOI the necessary rights of use to these IP RIGHTS solely for the MANUFACTURING of PRODUCT and/or the performance of SERVICES and/or performance of ADDITIONAL SERVICES, [***].

8.Defective Product

8.1.If and to the extent permitted by law, PRODUCT is delivered to UGX according to the conditions and SPECIFICATIONS outlined in this AGREEMENT subject to the checks by UGX under Section 8.2 and the inspection by IOI under Section 8.3. IOI makes no warranties, representations of guarantees nor any terms and/or conditions of any kind whatsoever, either expressed or implied whether by statute, common law, custom, course of dealing or otherwise, including any expressed or implied warranties of merchantability, non-infringement, fitness for a particular purpose other than those indicated in this AGREEMENT.

8.2.UGX or its designee(s) shall examine PRODUCT MANUFACTURED and delivered by or on behalf of IOI for compliance with the SPECIFICATIONS, shortage or chemical identity without undue delay as well as in line with the TECHNICAL RELEASE. Should any of PRODUCT fail to meet the SPECIFICATIONS, shortage or chemical identity, UGX shall inform IOI in writing without undue delay, [***] after identification of such defects. HIDDEN DEFECTS can be claimed in writing within [***] after being detected by UGX within [***] after the TECHNICAL RELEASE. If UGX fails to notify the defect within such a period, UGX shall be deemed to have accepted the defect.

8.3.In the event UGX notifies IOI within the period and for the reasons mentioned in Section 8.2 , IOI shall conduct its own evaluation within the time frame defined in the QTA. Following such evaluation and in case IOI confirms the non-conformity IOI will then repeat the MANUFACTURING and related SERVICES [***] until the defect is corrected. This is [***]. If the conformity is disputable, IOI and UGX jointly will engage a neutral third party expert to perform a neutral evaluation. The outcome will be binding for both parties.

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9.Indemnification for Third-Party Claims

9.1.Except for a claim arising out of [***] or [***] under this AGREEMENT, in the event of legal proceedings being instituted against IOI by a third party arising out of UGX's development, processing and commercialization of the Product, UGX shall indemnify and keep indemnified IOI in full against all damages, losses, injuries, costs and expenses in connection with such legal proceedings. IOI will inform UGX about any legal proceedings being instituted against IOI without delay. UGX shall control the respective legal proceedings but shall not settle any claim that admits fault on behalf of IOI without IOI's consent (not be unreasonably withheld).

9.2.In the event of legal proceedings being instituted against UGX by a third party arising out of [***] or [***] under this Agreement, IOI shall indemnify and keep indemnified UGX in full against all damages, losses, injuries, costs and expenses in connection with such legal proceedings. UGX will inform IOI about any legal proceedings being instituted against UGX without delay. IOI shall control the respective legal proceedings but shall not settle any claim without UGX's consent (not be unreasonably withheld).

9.3.If IOI’s cooperation is required in administrative proceedings, especially in proceedings relating to admission, customs or importation of PRODUCT, UGX indemnifies IOI for any liability which may arise out of this cooperation, except to the extent [***]. That applies, in particular, in cases, where [***]. The procedural requirements of Sections 9.1-9.2 shall apply to any indemnification claims by IOI under this Section 9.3.

10.Limitation of Liabilities

10.1.Subject to UGX’s obligation to pay under Section 4, the Parties’ overall liability arising out of or in connection with this AGREEMENT, whether in contract, tort, statutory or otherwise is [***] Euro per [***], or [***] in the event this AGREEMENT expires or is terminated for whatever reason before the end of a CALENDAR YEAR. The limitation under this Section 10.1 does not apply to each Party’s obligation to indemnify the other under [***] or any other liability that cannot be restricted by law.

10.2.Except for the indemnity under Section 9, each Party excludes any liability for [***] provided that such damages have not been [***].

10.3.EACH PARTY EXCLUDES ANY LIABILITY FOR SPECIAL, INDIRECT, INCIDENTAL, CONSEQUENTIAL OR PUNITIVE AND EXEMPLARY DAMAGES, RECALL COSTS, LOSS OF PROFIT ARISING OUT OF OR RELATED TO THIS AGREEMENT OR THE EXERCISE OF ITS RIGHTS HEREUNDER, HOWEVER CAUSED, PROVIDED THAT SUCH DAMAGES HAVE NOT BEEN CAUSED BY [***].

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11.Insurance

11.1.Either Party shall, at its sole cost and expense, obtain and maintain in force for the term of the AGREEMENT adequate and suitable insurance in the minimum amounts set forth below with a reputable insurance company to cover its liability under this AGREEMENT.

11.2.UGX will maintain a comprehensive products liability insurance, with combined single limits of [***] USD for each claim with respect to personal injury and/or damage to property and [***] USD aggregate.

11.3.IOI will maintain a comprehensive product liability insurance, with combined single limits of [***] USD for each claim with respect to personal injury and/or damage to property and [***] USD aggregate.

11.4.Such insurance must remain in place for the entire duration of this AGREEMENT and [***] after termination triggered in compliance with Section 13. For the avoidance of any doubt, each Party is allowed to change the insurer during the validity term of this Section 11.4 provided that all the conditions described in this Section 11 are properly met.

11.5.IOI will provide insurance certificates upon request to UGX. IOI must promptly notify UGX if any of such insurance is canceled, terminated or not renewed.

12.Force Majeure

Neither Party is liable to the other Party for failure or delay in performing its obligations to the extent and for so long as such failure or delay results from causes that were not reasonably foreseeable at the time of signing the AGREEMENT, are beyond the reasonable control of such Party, including but not limited to fires, earthquakes, floods, embargoes, wars, acts of war (whether war is declared or not), terrorist acts, insurrections, riots, civil commotion, strikes, lockouts or other labor disturbances, acts of God or other acts, omissions, pandemics or delays in acting by any administrative authority (each, a “Force Majeure”), and the effects of which cannot be avoided or overcome by such Party. In the event of the occurrence of Force Majeure, the Party affected must notify the other Party promptly of the Force Majeure event and its anticipated duration, and each Party will use its [***] to mitigate the adverse consequences.

13.Term and Termination

13.1.This AGREEMENT is effective as of the last date of signature (“Effective Date”) and will last for an indefinite period (“Term”). Each Party may terminate this AGREEMENT at will (without cause) with a pre-notice of [***] at any time.

13.2.If a Party commits a material breach of a material obligation of this AGREEMENT and does not cure such breach within [***] of receiving notice of such breach from the non-breaching Party, the non- breaching Party may terminate this AGREEMENT with immediate effect upon written notice to the breaching Party.

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13.3.Each Party shall also be entitled to terminate this AGREEMENT with [***] in case of MATERIAL CHANGE in CONTROL or BUSINESS MODEL of the respective other Party which affects such Party`s ability to fulfill its contractual obligations.

13.4.Either Party shall be entitled to terminate this AGREEMENT with [***] if the other Party fails to maintain the necessary rights, permits and approvals to perform the contractual obligations under this AGREEMENT.

13.5.Either Party may terminate in the event for FORCE MAJEURE lasting longer than [***].

13.6.In any event of termination (including termination at will by IOI, but excluding termination at will by UGX as per Section 13.1 and termination by IOI for UGX’s breach under Section 13.2) of this AGREEMENT triggered by any of the Parties or resulting from [***], UGX may by written notice to IOI seek assistance from IOI with respect to [***] and agreed to by IOI and UGX. IOI agrees to [***], which [***], with the exception of the [***]. Except as specifically set forth in this paragraph, IOI will not [***] and will not provide, disclose or teach or otherwise reveal IOI INTELLECTUAL PROPERTY or IOI BACKGROUND INTELLECTUAL PROPERTY, consistent with the principles set forth in Section 7.

14.Miscellaneous

14.1.No change of this AGREEMENT is valid unless it is in writing and signed by the Parties. This applies also to the foregoing sentence.

14.2.In case one of the sections is invalid or unenforceable, the other sections remain unaffected by this. The Parties shall negotiate in good faith if they wish to replace such invalid or unenforceable section.

14.3.Any notice or request required or permitted to be given under or in connection with this AGREEMENT or the subject matter hereof shall be given by prepaid registered or certified first-class airmail, recognized international carrier, e-mail or telefax to the recipient at its address set forth on the first page of this AGREEMENT or to such other address as may have therefore been furnished in writing by the recipient to the sending Party. Any such aforementioned notice or request concerning this AGREEMENT shall be effective upon receipt by the Party to which it is addressed.

14.4.Neither Party may assign or transfer this AGREEMENT or any rights or obligations hereunder, by operation or law or otherwise, without the prior written consent of the other Party, except that a Party may make such an assignment or transfer, by operation of law or otherwise, without the other Party’s consent to its insurers, its AFFILIATE(S) or to an entity that acquires all or substantially all the business

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of such Party to which this AGREEMENT relates, whether in a merger, consolidation, reorganization, acquisition, sale or otherwise. Notwithstanding anything to the contrary contained herein, in the event of an assignment to an AFFILIATE pursuant to this Section 14.4, the assigning Party consents, acknowledges, covenants and guarantees that it shall remain jointly and severally liable, along with the assignee, to the non-assigning Party for all the obligations contained herein. This AGREEMENT shall be binding on the successors and permitted assigns of the assigning Party, and the name of a Party appearing herein shall be deemed to include the name(s) of such Party’s successors and permitted assigns to the extent necessary to carry out the intent of this AGREEMENT. Any assignment or attempted assignment by either Party in violation of this Section 14.4, shall be null and void and of no legal effect.

14.5.This AGREEMENT and any potential subsequent amendment to it, may be executed in 2 (two) or more counterparts, each of which shall be deemed an original and all of which shall constitute together the same instrument. In the event that any signature is delivered by facsimile transmission, by e-signature or by e-mail delivery of a .pdf format data file, such signature shall create a valid and binding obligation of the party executing (or on whose behalf such signature is executed) with the same force and effect as if such facsimile, electronic signature or “.pdf” signature page were an original thereof.

14.6.Any controversy, claim or dispute arising out of or relating to this AGREEMENT, including any question regarding its existence, validity, breach or termination (a “DISPUTE”), shall be resolved in accordance with the following provisions:

a)Any DISPUTE shall be settled, if possible, through good-faith negotiation between the Parties at the Steering Committee (as set out in Section 5). Such good faith negotiations shall commence promptly upon a Party’s receipt of notice of any claim or dispute from the other Party and continue for a period of [***]. [***].

b)If the Parties do not reach an amicable settlement of the DISPUTE, it shall be submitted to mediation in accordance with the Swiss Rules of Mediation of the Swiss Arbitration Centre in force on the date when the request for mediation was submitted in accordance with these Rules. The seat of the mediation shall be Bern, in Switzerland, although the meetings may be held in Basel, Switzerland, or in Hamburg, Germany. The mediation shall be conducted in English or in German.

c)If the Parties do not reach a resolution of the DISPUTE by mediation within [***] from the date when the mediator(s) has (have) been confirmed or appointed by the Swiss Arbitration Centre, it shall be exclusively resolved by the courts of Bern, Switzerland.

14.7.This AGREEMENT shall be governed by and construed in accordance with the laws of Switzerland without reference to any rules of conflicts of law and excluding the United Nations Convention onContracts for the International Sale of Goods (“CISG”).

14.8.Each Party hereto has a duty of good faith and fair dealing in connection with its performance under this AGREEMENT. Each Party shall perform its obligations under this AGREEMENT in a diligent, legal, ethical and professional manner so as to advance the purposes and intent of this AGREEMENT.

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IN WITNESS WHEREOF, this AGREEMENT is executed as of the AGREEMENT Effective Date on behalf of the parties by their duly authorized representatives.

Ultragenyx Pharmaceutical Inc.	IOI Oleo GmbH
By: /s/ Siegfried Hackl	/s/ Rene Fresen
Siegfried Hackl	Rene Fresen
Printed Name	Printed Name
SVP Product Supply	Chief Marketing Officer
Title	Title
31-Mai-2023	15-June-2023
Date	Date

Ultragenyx Pharmaceutical Inc.	IOI Oleo GmbH
By: /s/ Dennis Huang	/s/ Mark Tuchen
Dennis Huang	Mark Tuchen
Printed Name	Printed Name
Chief Technical Ops Officer	Chief Financial Officer
Title	Title
06-June-2023	19-June-2023
Date	Date

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Appendix I

Commercial Terms

I.Forecast and Purchase Order

(i)The Parties hereby establish a forecast procedure, comprising a binding rolling forecast period and a non-binding long-term range as follows.

(ii)UGX will provide a good faith rolling forecast covering the [***] no later than the [***] of each [***], specifying the ordered quantity of PRODUCT, the number of batches and the expected DELIVERY DATE (“FORECAST”). IOI will have [***] after receipt to reject the FORECAST submitted by UGX and to provide an alternative production schedule.

(iii)The first [***] of the confirmed FORECAST shall be binding (“BINDING PERIOD”) to [***] to both Parties with respect to [***].

(iv)UGX will issue PURCHASE ORDERS upon confirmation of FORECAST reflecting the quantities of PRODUCT to be delivered during the BINDING PERIOD and their DELIVERY DATE. [***]. IOI can reject Purchase Order and DELIVERY DATE within [***] of receipt of such PURCHASE ORDER after which the Purchase Order and DELIVERY DATE will become binding on IOI. [***].

(v)In case a PURCHASE ORDER is changed by UGX and needs to be rescheduled within BINDING PERIOD, both Parties agree [***].

II.Delivery

(i)Any delivery of PRODUCT by IOI to UGX or to a THIRD-PARTY named by UGX shall be [***], unless otherwise agreed in writing by the Parties. IOI will package PRODUCT according to the requirement of UGX for transport in line with the QTA or mutually agreed on shipping procedures.

(ii)The transfer of property/title of PRODUCT will be upon payment by UGX of the respective invoice for PRODUCT.

(iii)In urgent cases, UGX may request in writing:

a)a QUARANTINED SHIPMENT;

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UGX assumes all risks, responsibilities and costs associated with a QUARANTINED SHIPMENT, unless the reason for the non-compliance of the PRODUCT is caused by IOI.

III.Prices and Payment

(i)Price for the MANUFACTURING of PRODUCT (“PRICE") is outlined in Appendix III for the [***] -“INITIAL TERM”). [***] is determined by the [***] within the [***].

(ii)If after the INITIAL TERM it is determined that [***] had been applied, the [***] will be applied after such determination. Any [***] differences therefore will either be a) [***] or b) [***].

(iii) The PRICE may be [***], effective on the [***] from IOI to UGX. Such [***] shall be based on [***] in [***]. Any [***] shall be based [***].

(iv)Payments shall be made by UGX in Euro and within [***] after receipt of a proper invoice.

(v)Invoices sent via email will be submitted to invoicing@ultragenyx.comand the responsible Joint Working Team member of UGX. For sake of clarity, IOI shall invoice UGX any batches of PRODUCT upon [***].

(vi)[***] (“OFFER”) following specific requests by UGX and shall become applicable upon UGX’s acceptance of an OFFER.

(vii)PRICE for PRODUCT and fee for ADDITIONAL SERVICES shall not contain [***]

IV.Third-Party Material

(i)All Services requiring materials that are purchased, procured, stored and tested by IOI shall be [***].

(ii)IOI will promptly inform UGX if it encounters [***], including [***] with respect to any [***]. In such an event, [***].

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V.Special Costs

All costs concerning [***]. In such a case, [***] of receipt of invoice and documentation of such amounts. As soon as possible, UGX will inform IOI about any administrative requirement applicable to IOI in force in any country where UGX is marketing commercial PRODUCT.

VI.Additional Services

Upon request by UGX, IOI will perform ADDITIONAL SERVICES, as long as [***]. If [***], the [***]. These additional services might be but are not limited to:

(i)[***];

(ii)Any [***] either requested by UGX (e.g. [***]) or resulting from any [***] requested by UGX, including [***],

(iii)[***] work

(iv)[***]specific for the manufacturing of PRODUCT

(v)Any [***] work

(vi)[***];

(vii)[***]. For the avoidance of doubt, [***]. For any other circumstance JOINT WORKING TEAM will engage in good faith to conclude the applicable fees.

(viii)[***].

IOI will [***] ADDITIONAL SERVICE to UGX by written OFFER referring to this AGREEMENT. Upon agreement between the Parties about such OFFER, IOI will provide the ADDITIONAL SERVICES as described in the respective OFFER.

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Appendix II

Compliance

I.Compliance Statement

To the extent applicable, IOI shall inform itself of and comply with applicable anti-corruption legislation, including legislation enacted pursuant to the 1997 OECD Convention on Combating Bribery of Foreign Public Officials in International Business Transactions (the “OECD Convention”), and the Foreign Corrupt Practices Act of 1977, as amended (15 U.S.C. §§78dd-1, et. seq.) (the “FCPA”). If applicable to the MANUFACTURE, SERVICES and ADDITIONAL SERVICES provided hereunder, IOI declares that it understands the provisions of the OECD Convention and the FCPA and agrees not to breach any such legislation or to cause UGX to breach any such legislation. IOI further agrees that, if applicable, it will educate its personnel and contractors engaged in MANUFACTURE, providing SERVICES and ADDITIONAL SERVICES to UGX hereunder in relation to such legislation. IOI agrees it has not, and covenants that it will not, in connection with the conduct of its business activities, promise, authorize, ratify or offer to make, or take any act in furtherance of any payment, contribution, gift, reimbursement or other transfer of anything of value, or any solicitation, directly or indirectly: (i) to any individual including government officials; or (ii) to an intermediary for payment to any individual including government officials; or (iii) to any political party for the purpose or effect of public or commercial bribery, acceptance of or acquiescence in extortion, kickbacks or other unlawful, illegal or improper means. IOI has not, nor to the knowledge of IOI, have any of the IOI’s directors, officers, agents, stockholders or employees acting on behalf of IOI made any false or artificial entries on any of its books or records for any reason. IOI also represents, but only to the best of their knowledge, that, except as disclosed to UGX in writing, it will collaborate with UGX to the best of its ability to represent on a CALENDAR YEAR basis whether neither it nor any of its officers, directors, shareholders or beneficial owners is (i) an officer or employee of a government or any department, agency or instrumentality thereof (including a government-owned or controlled commercial enterprise), (ii) an officer or employee of a public international organization, (iii) a person who acts in any official capacity for or on behalf of any government or department, agency, instrumentality or public international organization, or (iv) a political party official or candidate for political office (each, a “GOVERNMENT OFFICIAL”). IOI will immediately disclose to UGX any current or future affiliation or association between itself and any GOVERNMENT OFFICIAL as long as it becomes aware of that.

II.Data Privacy

Each Party shall collect, use, retain and disclose any personal data provided or belonging to the other Party in a fair, transparent and secure way in accordance to any Applicable Law. Each Party shall (i) use the other Party personal data only under such Party’s instructions in writing and not use it for any purpose other than the performance of this AGREEMENT; (ii) ensure that effective organisational and security measures (both technological and physical) are applied to all personal data of the other Party to ensure the privacy of affected individuals; (iii) appoint a representative who is accountable for data privacy and security; (iv) ensure information is protected and kept secure at all times from unauthorised use, damage, disclosure, diversion or removal, whether through accident, improper act or breach of trust; (v) ensure employees who will have access to the other Party’s personal data are appropriately trained in their responsibilities around processing and protecting the personal data.

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III.Documentation of Business Transactions

The documentation of any and all business transactions must be complete, transparent, and in compliance with the statutory provisions as well as with any provisions and processes.

IV.Social Responsibility

IOI respects the dignity of every human being and is committed to compliance with and the protection of human rights.

IOI does not tolerate any kind of child labor as well as any exploitation of children and adolescents. The minimum age for admission to employment must not be under the age for the fulfillment of compulsory education and in no case under 15 (fifteen) years.

IOI disapproves of any form of forced labor.

V.No Discrimination

IOI creates a working atmosphere characterized by respectful cooperation and to strictly oppose any kind of discrimination on grounds of race or ethnic origin, gender, religion or philosophy of life, disability, age, or sexual identity.

VI.EHS (Environment, Health and Safety)

IOI undertakes to operate in a safe and responsible manner with respect to the environment and health of employees, customers and the communities where they operate.

IOI will not compromise environmental, health or safety values for other interests; value human life above all else and manage risks accordingly.

IOI pursues and continually improves an EHS system and processes to achieve an EHS incident-free environment.

IOI agrees to always comply with applicable laws and set standards for suppliers.

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Appendix III Prices and Fees

[***]

24

Appendix IV

QUALITY AND TECHNICAL AGREEMENT (QTA)

The current version of the QTA executed separately by the Parties.

25

Appendix V

PRODUCT SPECIFICATION

The current version of [***]

26

Appendix VI

RAW MATERIAL SPECIFICATIONS

[***]

27

Appendix VII

[***]

28

Appendix VIII

THIRD PARTY laboratories

THIRD-PARTY labs are, but are not limited to:

[***]

29

EX-10.30

Exhibit 10.30

Name:

Number of Shares of Stock subject to Stock Option:

Price Per Share:

Date of Grant:

Vesting Start Date:

Ultragenyx Pharmaceutical Inc.
2023 Incentive Plan

incentive Stock Option Agreement

This agreement (this “Agreement”) evidences a stock option granted by Ultragenyx Pharmaceutical Inc. (the “Company”) to the undersigned (the “Optionee”) pursuant to and subject to the terms of the Ultragenyx Pharmaceutical Inc. 2023 Incentive Plan (as amended from time to time, the “Plan”),which is incorporated herein by reference.

1.Grant of Stock Option. The Company grants to the Optionee on the date set forth above (the “Date of Grant”) an option (the “Stock Option”) to purchase, on the terms provided herein and in the Plan, up to the number of shares of Stock set forth above (the “Shares”) with an exercise price per Share as set forth above, in each case subject to adjustment pursuant to Section 7(b) of the Plan in respect of transactions occurring after the date hereof.

2.Meaning of Certain Terms. Except as otherwise defined herein, all capitalized terms used herein have the same meaning as in the Plan. The following terms have the following meanings:

(a)“Beneficiary” means, in the event of the Optionee’s death, the beneficiary named in the written designation (in form acceptable to the Administrator) most recently filed with the Administrator by the Optionee prior to the Optionee’s death and not subsequently revoked, or, if there is no such designated beneficiary, the executor or administrator of the Optionee’s estate. An effective beneficiary designation will be treated as having been revoked only upon receipt by the Administrator, prior to the Optionee’s death, of an instrument of revocation in form acceptable to the Administrator.

(b)“Option Holder” means the Optionee or, if as of the relevant time the Stock Option has passed to a Beneficiary, the Beneficiary.

3.Vesting; Method of Exercise; Treatment of the Stock Option Upon Cessation of Employment.

(a)Vesting. As used herein with respect to the Stock Option or any portion thereof, the term “vest” means to become exercisable and the term “vested” as applied to any outstanding Stock Option means that the Stock Option is then exercisable, subject in each case to the terms of the Plan. Unless earlier terminated, forfeited, relinquished or expired, the Stock Option will vest as to 1/4th of the Shares initially subject to the Stock Option on the first (1st) anniversary of the Date of Grant (the "Anniversary Date"); thereafter, 1/48th of the Shares initially subject to the Stock Option shall vest on each month as measured by the Anniversary Date. Notwithstanding the foregoing, Shares subject to the Stock Option shall not vest on any vesting date

DOCPROPERTY DocXDocID DMS=InterwovenIManage Format=<<NUM>>_<<VER>> PRESERVELOCATION \* MERGEFORMAT 39776746_3

unless the Optionee has remained in continuous Employment from the Date of Grant through such vesting date.

(b)Exercise of the Stock Option. No portion of the Stock Option may be exercised until such portion vests. Each election to exercise any vested portion of the Stock Option will be subject to the terms and conditions of the Plan and shall be in writing, signed by the Option Holder (or in such other form as is acceptable to the Administrator). Each such written exercise election must be received by the Company at its principal office or by such other party as the Administrator may prescribe and be accompanied by payment in full as provided in the Plan. The exercise price may be paid (i) by cash or check acceptable to the Administrator, (ii) to the extent permitted by the Administrator, through a broker-assisted cashless exercise program acceptable to the Administrator, (iii) by such other means, if any, as may be acceptable to the Administrator, or (iv) by any combination of the foregoing permissible forms of payment. In the event that the Stock Option is exercised by a person other than the Optionee, the Company will be under no obligation to deliver shares hereunder unless and until it is satisfied as to the authority of the Option Holder to exercise the Stock Option and compliance with applicable securities laws. The latest date on which the Stock Option or any portion thereof may be exercised will be the 10th anniversary of the Date of Grant (the “Final Exercise Date”). If the Stock Option is not exercised by the Final Exercise Date the Stock Option or any remaining portion thereof will thereupon immediately terminate.

(c)Treatment of the Stock Option Upon Cessation of Employment. If the Optionee’s Employment ceases, the Stock Option, to the extent not already vested will be immediately forfeited, and any vested portion of the Stock Option that is then outstanding will be treated as follows:

(i)Subject to clauses (ii) and (iii) below and Section 4 of this Agreement, the Stock Option, to the extent vested immediately prior to the cessation of the Optionee’s Employment, will remain exercisable until the earlier of (A) the date that is three months following the date of such cessation of Employment, or (B) the Final Exercise Date, and except to the extent previously exercised as permitted by this Section 3(c)(i) will thereupon immediately terminate.

(ii)Subject to clauses (iii) below and Section 4 of this Agreement, the Stock Option, to the extent vested immediately prior to the cessation of the Optionee’s Employment due to death, will remain exercisable until the earlier of (A) the first anniversary of the Optionee’s death or (B) the Final Exercise Date, and except to the extent previously exercised as permitted by this Section 3(c)(ii) will thereupon immediately terminate.

(iii)If the Optionee’s Employment is terminated by the Company and its subsidiaries in connection with an act or failure to act constituting Cause (as the Administrator, in its sole discretion, may determine), or such termination occurs in circumstances that in the determination of the Administrator would have entitled the Company and its subsidiaries to terminate the Optionee’s Employment for Cause, the Stock Option (whether or not vested) will immediately terminate and be forfeited upon such termination.

4.Forfeiture; Recovery of Compensation.

(a)The Administrator may cancel, rescind, withhold or otherwise limit or restrict the Stock Option at any time if the Optionee is not in compliance with all applicable provisions of this Agreement and the Plan.

(b)By accepting the Stock Option, the Optionee expressly acknowledges and agrees that his or her rights, and those of any permitted transferee of the Stock Option, under the Stock Option to any Stock acquired under the Stock Option or proceeds from the disposition thereof, are subject to Section 6(a)(v) of the Plan (including any successor provision). Nothing in the preceding sentence shall be construed as limiting the general application of Section 8 of this Agreement.

5.Transfer of Stock Option. The Stock Option may not be transferred except as expressly permitted under Section 6(a)(iii) of the Plan.

6.Taxes.

(a)Withholding. If at the time this Stock Option is exercised the Company determines that under applicable law and regulations it could be liable for the withholding of any federal or state tax upon exercise or with respect to a disposition of any Stock acquired upon exercise of this Stock Option, the Optionee expressly acknowledges and agrees that the Optionee’s rights hereunder, including the right to be issued shares upon exercise, are subject to the Optionee promptly paying to the Company in cash (or by such other means as may be acceptable to the Administrator in its discretion) all taxes required to be withheld. No shares will be transferred pursuant to the exercise of this Stock Option unless and until the person exercising this Stock Option has remitted to the Company an amount in cash sufficient to satisfy any federal, state, or local withholding tax requirements, or has made other arrangements satisfactory to the Company with respect to such taxes. The Optionee authorizes the Company and its subsidiaries to withhold such amount from any amounts otherwise owed to the Optionee, but nothing in this sentence shall be construed as relieving the Optionee of any liability for satisfying his or her obligation under the preceding provisions of this Section.

(b)Disqualifying Disposition. If the Optionee disposes of the Shares acquired upon exercise of this Stock Option within two years from the Grant Date or one year after such Shares were acquired pursuant to the exercise of this Stock Option, within 15 days of such disposition, the Optionee shall notify the Company in writing of such disposition.

(c)Annual Limit for Incentive Stock Options. To the extent that the aggregate fair market value (determined at the time of grant) of the shares of Stock with respect to which this Stock Option and all other incentive stock options the Optionee holds are exercisable for the first time during any calendar year (under all plans of the Company and its related corporations) exceeds $100,000, the options held by such Optionee or portions thereof that exceed such limit (according to the order in which they were granted in accordance with the regulations under Section 422 of the Code) shall be treated as a non-qualified stock option.

(d)Limitation on Liability. The Optionee acknowledges and agrees that the Company or the Administrator may take any action permitted under the Plan without regard to the effect such action may have on the status of this Stock Option as an incentive

stock option under Section 422 of the Code and that such actions may cause this Stock Option to fail to be treated as an incentive stock option under Section 422 of the Code. The Optionee further acknowledges and agrees that neither the Company, nor any of its Affiliates, nor the Administrator, nor any person acting on behalf of the Company, any of its Affiliates, or the Administrator, will be liable to the Optionee or to the estate or beneficiary of the Optionee or to any other person by reason of the failure the Stock Option to satisfy the requirements of Section 422 of the Code.

7.Effect on Employment. Neither the grant of the Stock Option, nor the issuance of Shares upon exercise of the Stock Option, will give the Optionee any right to be retained in the employ or service of the Company or any of its Affiliates, affect the right of the Company or any of its Affiliates to discharge or discipline such Optionee at any time, or affect any right of such Optionee to terminate his or her Employment at any time.

8.Provisions of the Plan. This Agreement is subject in its entirety to the provisions of the Plan, which are incorporated herein by reference. A copy of the Plan as in effect on the Date of Grant has been furnished to the Optionee. By exercising all or any part of the Stock Option, the Optionee agrees to be bound by the terms of the Plan and this Agreement. In the event of any conflict between the terms of this Agreement and the Plan, the terms of the Plan shall control.

9.Acknowledgements. The Optionee acknowledges and agrees that (a) this Agreement may be executed in two or more counterparts, each of which shall be an original and all of which together shall constitute one and the same instrument, (b) this agreement may be executed and exchanged using facsimile, portable document format (PDF) or electronic signature, which, in each case, shall constitute an original signature for all purposes hereunder and (c) such signature by the Company will be binding against the Company and will create a legally binding agreement when this Agreement is countersigned by the Optionee.

The Stock Option evidenced by this Agreement is intended to be an incentive stock option under Section 422 of the Code and is granted to the Optionee in connection with the Optionee’s employment by or service to the Company and its qualifying subsidiaries. For purposes of the immediately preceding sentence, “qualifying subsidiary” means a subsidiary of the Company as to which the Company has a “controlling interest” as described in Treas. Regs. §1.409A-1(b)(5)(iii)(E)(1).

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IN WITNESS WHEREOF, the Company has caused this Agreement to be executed by its duly authorized officer.

ULTRAGENYX PHARMACEUTICAL Inc.

By: /s/ Emil Kakkis

Name: Emil Kakkis, M.D., Ph.D.

Title: Chief Executive Officer

Dated:

Acknowledged and Agreed:

By_______________________

EX-10.31

Exhibit 10.31

Name:

Number of Shares of Stock subject to Stock Option:

Price Per Share:

Date of Grant:

Vesting Start Date:

Ultragenyx Pharmaceutical Inc.
2023 Incentive Plan

Non-statutory Stock Option Agreement (Employees)

This agreement (this “Agreement”) evidences a stock option granted by Ultragenyx Pharmaceutical Inc. (the “Company”) to the undersigned (the “Optionee”) pursuant to and subject to the terms of the Ultragenyx Pharmaceutical Inc. 2023 Incentive Plan (as amended from time to time, the “Plan”),which is incorporated herein by reference.

1.Grant of Stock Option. The Company grants to the Optionee on the date set forth above (the “Date of Grant”) an option (the “Stock Option”) to purchase, on the terms provided herein and in the Plan, up to the number of shares of Stock set forth above (the “Shares”) with an exercise price per Share as set forth above, in each case subject to adjustment pursuant to Section 7(b) of the Plan in respect of transactions occurring after the date hereof.

2.Meaning of Certain Terms. Except as otherwise defined herein, all capitalized terms used herein have the same meaning as in the Plan. The following terms have the following meanings:

(a)“Beneficiary” means, in the event of the Optionee’s death, the beneficiary named in the written designation (in form acceptable to the Administrator) most recently filed with the Administrator by the Optionee prior to the Optionee’s death and not subsequently revoked, or, if there is no such designated beneficiary, the executor or administrator of the Optionee’s estate. An effective beneficiary designation will be treated as having been revoked only upon receipt by the Administrator, prior to the Optionee’s death, of an instrument of revocation in form acceptable to the Administrator.

(b)“Option Holder” means the Optionee or, if as of the relevant time the Stock Option has passed to a Beneficiary, the Beneficiary.

3.Vesting; Method of Exercise; Treatment of the Stock Option Upon Cessation of Employment.

(a)Vesting. As used herein with respect to the Stock Option or any portion thereof, the term “vest” means to become exercisable and the term “vested” as applied to any outstanding Stock Option means that the Stock Option is then exercisable, subject in each case to the terms of the Plan. Unless earlier terminated, forfeited, relinquished or expired, the Stock Option will vest as to 1/4th of the Shares initially subject to the Stock Option on the first (1st) anniversary of the Date of Grant (the "Anniversary Date"); thereafter, 1/48th of the Shares initially subject to the Stock Option shall vest on each month as measured by the Anniversary Date. Notwithstanding the foregoing, Shares subject to the Stock Option shall not vest on any vesting date

unless the Optionee has remained in continuous Employment from the Date of Grant through such vesting date.

(b)Exercise of the Stock Option. No portion of the Stock Option may be exercised until such portion vests. Each election to exercise any vested portion of the Stock Option will be subject to the terms and conditions of the Plan and shall be in writing, signed by the Option Holder (or in such other form as is acceptable to the Administrator). Each such written exercise election must be received by the Company at its principal office or by such other party as the Administrator may prescribe and be accompanied by payment in full as provided in the Plan. The exercise price may be paid (i) by cash or check acceptable to the Administrator, (ii) to the extent permitted by the Administrator, through a broker-assisted cashless exercise program acceptable to the Administrator, (iii) by such other means, if any, as may be acceptable to the Administrator, or (iv) by any combination of the foregoing permissible forms of payment. In the event that the Stock Option is exercised by a person other than the Optionee, the Company will be under no obligation to deliver shares hereunder unless and until it is satisfied as to the authority of the Option Holder to exercise the Stock Option and compliance with applicable securities laws. The latest date on which the Stock Option or any portion thereof may be exercised will be the 10th anniversary of the Date of Grant (the “Final Exercise Date”); provided, however, if at such time the Optionee is prohibited by applicable law from exercising the Stock Option, the Final Exercise Date will be automatically extended to thirty (30) days following the date the Optionee is no longer prohibited from exercising the Stock Option. If the Stock Option is not exercised by the Final Exercise Date the Stock Option or any remaining portion thereof will thereupon immediately terminate.

(c)Treatment of the Stock Option Upon Cessation of Employment. If the Optionee’s Employment ceases, the Stock Option, to the extent not already vested will be immediately forfeited, and any vested portion of the Stock Option that is then outstanding will be treated as follows:

(i)Subject to clauses (ii) and (iii) below and Section 4 of this Agreement, the Stock Option, to the extent vested immediately prior to the cessation of the Optionee’s Employment, will remain exercisable until the earlier of (A) the date that is three months following the date of such cessation of Employment, or (B) the Final Exercise Date, and except to the extent previously exercised as permitted by this Section 3(c)(i) will thereupon immediately terminate.

(ii)Subject to clauses (iii) below and Section 4 of this Agreement, the Stock Option, to the extent vested immediately prior to the cessation of the Optionee’s Employment due to death, will remain exercisable until the earlier of (A) the first anniversary of the Optionee’s death or (B) the Final Exercise Date, and except to the extent previously exercised as permitted by this Section 3(c)(ii) will thereupon immediately terminate.

(iii)If the Optionee’s Employment is terminated by the Company and its subsidiaries in connection with an act or failure to act constituting Cause (as the Administrator, in its sole discretion, may determine), or such termination occurs in circumstances that in the determination of the Administrator would have entitled the Company and its subsidiaries to terminate the Optionee’s Employment for Cause, the Stock Option (whether

or not vested) will immediately terminate and be forfeited upon such termination.

4.Forfeiture; Recovery of Compensation.

(a)The Administrator may cancel, rescind, withhold or otherwise limit or restrict the Stock Option at any time if the Optionee is not in compliance with all applicable provisions of this Agreement and the Plan.

(b)By accepting the Stock Option, the Optionee expressly acknowledges and agrees that his or her rights, and those of any permitted transferee of the Stock Option, under the Stock Option to any Stock acquired under the Stock Option or proceeds from the disposition thereof, are subject to Section 6(a)(v) of the Plan (including any successor provision). Nothing in the preceding sentence shall be construed as limiting the general application of Section 8 of this Agreement.

5.Transfer of Stock Option. The Stock Option may not be transferred except as expressly permitted under Section 6(a)(iii) of the Plan.

6.Withholding. The exercise of this Stock Option will give rise to “wages” subject to withholding. The Optionee expressly acknowledges and agrees that the Optionee’s rights hereunder, including the right to be issued shares upon exercise, are subject to the Optionee promptly paying to the Company in cash (or by such other means as may be acceptable to the Administrator in its discretion) all taxes required to be withheld. No shares will be transferred pursuant to the exercise of this Stock Option unless and until the person exercising this Stock Option has remitted to the Company an amount in cash sufficient to satisfy any federal, state, or local withholding tax requirements, or has made other arrangements satisfactory to the Company with respect to such taxes. The Optionee authorizes the Company and its subsidiaries to withhold such amount from any amounts otherwise owed to the Optionee, but nothing in this sentence shall be construed as relieving the Optionee of any liability for satisfying his or her obligation under the preceding provisions of this Section.

7.Effect on Employment. Neither the grant of the Stock Option, nor the issuance of Shares upon exercise of the Stock Option, will give the Optionee any right to be retained in the employ or service of the Company or any of its Affiliates, affect the right of the Company or any of its Affiliates to discharge or discipline such Optionee at any time, or affect any right of such Optionee to terminate his or her Employment at any time.

8.Provisions of the Plan. This Agreement is subject in its entirety to the provisions of the Plan, which are incorporated herein by reference. A copy of the Plan as in effect on the Date of Grant has been furnished to the Optionee. By exercising all or any part of the Stock Option, the Optionee agrees to be bound by the terms of the Plan and this Agreement. In the event of any conflict between the terms of this Agreement and the Plan, the terms of the Plan shall control.

9.Acknowledgements. The Optionee acknowledges and agrees that (a) this Agreement may be executed in two or more counterparts, each of which shall be an original and all of which together shall constitute one and the same instrument, (b) this agreement may be executed and exchanged using facsimile, portable document format (PDF) or electronic signature, which, in each case, shall constitute an original signature for all purposes hereunder and (c) such signature by the Company will be binding against the Company and will create a legally binding agreement when this Agreement is countersigned by the Optionee.

The Stock Option evidenced by this Agreement is a non-statutory option (that is, an option that does not qualify as an incentive stock option under Section 422 of the Code) and is granted to the

Optionee in connection with the Optionee’s employment by or service to the Company and its qualifying subsidiaries. For purposes of the immediately preceding sentence, “qualifying subsidiary” means a subsidiary of the Company as to which the Company has a “controlling interest” as described in Treas. Regs. §1.409A-1(b)(5)(iii)(E)(1).

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IN WITNESS WHEREOF, the Company has caused this Agreement to be executed by its duly authorized officer.

ULTRAGENYX PHARMACEUTICAL Inc.

By: /s/ Emil Kakkis

Name: Emil Kakkis, M.D., Ph.D.

Title: Chief Executive Officer

Dated:

Acknowledged and Agreed:

By_______________________

EX-10.32

Exhibit 10.32

Name:

Number of Restricted Stock Units subject to Award:

Date of Grant:

ULTRAGENYX PHARMACEUTICAL INC.

2023 INCENTIVE PLAN

RESTRICTED STOCK UNIT AGREEMENT (EMPLOYEES)

This agreement (this “Agreement”) evidences an award (the “Award”) of restricted stock units (the “Restricted Stock Units”) granted by Ultragenyx Pharmaceutical Inc. (the “Company”) to the undersigned (the “Grantee”) pursuant to and subject to the terms of the Ultragenyx Pharmaceutical Inc. 2023 Incentive Plan (as amended from time to time, the “Plan”), which is incorporated herein by reference.

1. Grant of Restricted Stock Units. The Company grants to the Grantee on the date set forth above (the “Date of Grant”) an award consisting of the right to receive on the terms provided herein and in the Plan, one share of Stock with respect to each Restricted Stock Unit forming part of the Award, in each case, subject to adjustment pursuant to Section 7(b) of the Plan in respect of transactions occurring after the date hereof.

2. Meaning of Certain Terms. Except as otherwise defined herein, all capitalized terms used herein have the same meaning as in the Plan.

3. Vesting. Unless earlier terminated, forfeited, relinquished or expired, the Restricted Stock Units shall vest as follows: 1/4th of the underlying shares shall vest on the first (1st) anniversary of the Date of Grant (the "Anniversary Date"); thereafter, 25% of the underlying shares shall vest each year as measured from the Anniversary Date.

4. Delivery of Stock. The Company shall deliver to the Grantee as soon as practicable upon the vesting of the Restricted Stock Units or any portion thereof, but in all events no later than March 15th of the year following the year in which such Restricted Stock Units vest, one share of Stock with respect to each such vested Restricted Stock Unit, subject to the terms of the Plan and this Agreement.

5. Dividends; Other Rights. The Award shall not be interpreted to bestow upon the Grantee any equity interest or ownership in the Company or any Affiliate prior to the date on which the Company delivers shares of Stock to the Grantee (if any). The Grantee is not entitled to vote any shares of Stock by reason of the granting of this Award or to receive or be credited with any dividends declared and payable on any share of Stock prior to the date on which any such share is delivered to the Grantee hereunder. The Grantee shall have the rights of a shareholder only as to those shares of Stock, if any, that are actually delivered under this Award.

6. Forfeiture; Recovery of Compensation.

(a) The Administrator may cancel, rescind, withhold or otherwise limit or restrict the Award at any time if the Grantee is not in compliance with all applicable provisions of this Agreement and the Plan.

(b) By accepting the Award the Grantee expressly acknowledges and agrees that his or her rights, and those of any permitted transferee of the Award, under the Award to any Stock acquired under the Award or proceeds from the disposition thereof, are subject to Section 6(a)(v) of the Plan (including any successor provision). Nothing in the preceding sentence shall be construed as limiting the general application of Section 10 of this Agreement.

7. Nontransferability. Neither the Award nor the Restricted Stock Units may be transferred except as expressly permitted under Section 6(a)(iii) of the Plan.

8. Certain Tax Matters.

(a) The Grantee expressly acknowledges and agrees that the Grantee’s rights hereunder, including the right to be issued shares of Stock upon the vesting of the Restricted Stock Units (or any portion thereof), are subject to the Grantee’s promptly paying, or in respect of any later requirement of withholding being liable promptly to pay at such time as such withholdings are due, to the Company in cash (or by such other means as may be acceptable to the Administrator in its discretion) all taxes required to be withheld, if any (the “Tax Withholding Obligation”). No shares of Stock will be transferred pursuant to the vesting of the Restricted Stock Units (or any portion thereof) unless and until the Grantee or the person then holding the Award has remitted to the Company an amount in cash sufficient to satisfy any federal, state, or local withholding tax requirements then due and has committed (and by accepting this Award the Grantee shall be deemed to have committed) to pay in cash all tax withholdings required at any later time in respect of the transfer of such shares, or has made other arrangements satisfactory to the Company with respect to such taxes. The Grantee also authorizes the Company and its subsidiaries to withhold such amount from any amounts otherwise owed to the

Grantee, but nothing in this sentence shall be construed as relieving the Grantee of any liability for satisfying his or her obligations under the preceding provisions of this Section.

(b) The Grantee expressly acknowledges that the Grantee’s acceptance of this Agreement constitutes the Grantee’s instruction and authorization to the Company and any brokerage firm determined acceptable to the Company for such purpose to sell on the Grantee’s behalf a whole number of shares from those shares of Stock issuable to the Grantee as the Company determines to be appropriate to generate cash proceeds sufficient to satisfy the applicable Tax Withholding Obligation, and to transfer the proceeds from the sale of such Stock from the Grantee’s securities account established with the brokerage service provider for the settlement of the Grantee’s vested Restricted Stock Units to any account held in the name of the Company. Such shares will be sold on the date of vesting or as soon thereafter as practicable. Grantee will be responsible for all brokers’ fees and other costs of sale, which fees and costs may be deducted from the proceeds of the foregoing sale of Stock, and Grantee agrees to indemnify and hold the Company and any brokerage firm selling such Stock harmless from any losses, costs, damages, or expenses relating to any such sale. To the extent the proceeds of such sale exceed Grantee’s Tax Withholding Obligation, such excess cash will be deposited into the securities account established with the brokerage service provider for the settlement of Grantee’s vested Restricted Stock Units. Grantee acknowledges that the Company or its designee is under no obligation to arrange for such sale at any particular price, and that the proceeds of any such sale may not be sufficient to satisfy Grantee’s Tax Withholding Obligation. Accordingly, Grantee agrees to pay to the Company as soon as practicable, including through additional payroll withholding, any amount of the Tax Withholding Obligation that is not satisfied by the sale of shares described above. Unless otherwise authorized by the Administrator in its sole discretion, the sale of Stock will be the primary method used by the Company to satisfy the applicable Tax Withholding Obligation.

(c) The Grantee expressly acknowledges that because this Award consists of an unfunded and unsecured promise by the Company to deliver Stock in the future, subject to the terms hereof, it is not possible to make a so-called “83(b) election” with respect to the Award.

9. Effect on Employment. Neither the grant of the Award, nor the issuance of shares of Stock upon vesting of the Award, will give the Grantee any right to be retained in the employ or service of the Company or any of its Affiliates, affect the right of the Company or any of its Affiliates to discharge or discipline such Grantee at any time, or affect any right of such Grantee to terminate his or her Employment at any time.

10. Provisions of the Plan. This Agreement is subject in its entirety to the provisions of the Plan, which are incorporated herein by reference. A copy of the Plan as in effect on the Date of Grant has been furnished to the Grantee. By accepting the Award, the Grantee agrees to be bound by the terms of the Plan and this Agreement. In the event of any conflict between the terms of this Agreement and the Plan, the terms of the Plan shall control.

11. Acknowledgments. The Grantee acknowledges and agrees that (a) this Agreement may be executed in two or more counterparts, each of which shall be an original and all of which together shall constitute one and the same instrument, (b) this agreement may be executed and exchanged using facsimile, portable document format (PDF) or electronic signature, which, in each case, shall constitute an original signature for all purposes hereunder and (c) such signature by the Company will be binding against the Company and will create a legally binding agreement when this Agreement is countersigned by the Grantee.

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IN WITNESS WHEREOF, the Company has caused this Agreement to be executed by its duly authorized officer.

ULTRAGENYX PHARMACEUTICAL INC.

 /s/ Emil Kakkis

Emil Kakkis, M.D., Ph.D.

Chief Executive Officer

Dated:

Acknowledged and Agreed:

By

EX-10.33

Exhibit 10.33

Name:

Number of Shares of Stock subject to Stock Option:

Price Per Share:

Date of Grant:

Vesting Start Date:

Ultragenyx Pharmaceutical Inc.
2023 Incentive Plan

Non-statutory Stock Option Agreement (Directors)

This agreement (this “Agreement”) evidences a stock option granted by Ultragenyx Pharmaceutical Inc. (the “Company”) to the undersigned (the “Optionee”) pursuant to and subject to the terms of the Ultragenyx Pharmaceutical Inc. 2023 Incentive Plan (as amended from time to time, the “Plan”),which is incorporated herein by reference.

1.Grant of Stock Option. The Company grants to the Optionee on the date set forth above (the “Date of Grant”) an option (the “Stock Option”) to purchase, on the terms provided herein and in the Plan, up to the number of shares of Stock set forth above (the “Shares”) with an exercise price per Share as set forth above, in each case subject to adjustment pursuant to Section 7(b) of the Plan in respect of transactions occurring after the date hereof.

2.Meaning of Certain Terms. Except as otherwise defined herein, all capitalized terms used herein have the same meaning as in the Plan. The following terms have the following meanings:

(a)“Beneficiary” means, in the event of the Optionee’s death, the beneficiary named in the written designation (in form acceptable to the Administrator) most recently filed with the Administrator by the Optionee prior to the Optionee’s death and not subsequently revoked, or, if there is no such designated beneficiary, the executor or administrator of the Optionee’s estate. An effective beneficiary designation will be treated as having been revoked only upon receipt by the Administrator, prior to the Optionee’s death, of an instrument of revocation in form acceptable to the Administrator.

(b)“Option Holder” means the Optionee or, if as of the relevant time the Stock Option has passed to a Beneficiary, the Beneficiary.

3.Vesting; Method of Exercise; Treatment of the Stock Option Upon Cessation of Employment.

(a)Vesting. As used herein with respect to the Stock Option or any portion thereof, the term “vest” means to become exercisable and the term “vested” as applied to any outstanding Stock Option means that the Stock Option is then exercisable, subject in each case to the terms of the Plan. Unless earlier terminated, forfeited, relinquished or expired, the Stock Option will vest as to all of the Shares initially subject to the Stock Option on the earlier of (i) the first anniversary of the Date of Grant or (ii) the date of the Company's annual meeting of stockholders first held after the Date of Grant. Notwithstanding the foregoing, Shares subject to the Stock Option shall not

vest on any vesting date unless the Optionee has remained in continuous Employment from the Date of Grant through such vesting date.

(b)Exercise of the Stock Option. No portion of the Stock Option may be exercised until such portion vests. Each election to exercise any vested portion of the Stock Option will be subject to the terms and conditions of the Plan and shall be in writing, signed by the Option Holder (or in such other form as is acceptable to the Administrator). Each such written exercise election must be received by the Company at its principal office or by such other party as the Administrator may prescribe and be accompanied by payment in full as provided in the Plan. The exercise price may be paid (i) by cash or check acceptable to the Administrator, (ii) to the extent permitted by the Administrator, through a broker-assisted cashless exercise program acceptable to the Administrator, (iii) by such other means, if any, as may be acceptable to the Administrator, or (iv) by any combination of the foregoing permissible forms of payment. In the event that the Stock Option is exercised by a person other than the Optionee, the Company will be under no obligation to deliver shares hereunder unless and until it is satisfied as to the authority of the Option Holder to exercise the Stock Option and compliance with applicable securities laws. The latest date on which the Stock Option or any portion thereof may be exercised will be the 10th anniversary of the Date of Grant (the “Final Exercise Date”); provided, however, if at such time the Optionee is prohibited by applicable law from exercising the Stock Option, the Final Exercise Date will be automatically extended to thirty (30) days following the date the Optionee is no longer prohibited from exercising the Stock Option. If the Stock Option is not exercised by the Final Exercise Date the Stock Option or any remaining portion thereof will thereupon immediately terminate.

(c)Treatment of the Stock Option Upon Cessation of Employment. If the Optionee’s Employment ceases, the Stock Option, to the extent not already vested will be immediately forfeited, and any vested portion of the Stock Option that is then outstanding will be treated as follows:

(i)Subject to clauses (ii) and (iii) below and Section 4 of this Agreement, the Stock Option, to the extent vested immediately prior to the cessation of the Optionee’s Employment, will remain exercisable until the earlier of (A) the date that is 24 months following the date of such cessation of Employment, or (B) the Final Exercise Date, and except to the extent previously exercised as permitted by this Section 3(c)(i) will thereupon immediately terminate.

(ii)Subject to clauses (iii) below and Section 4 of this Agreement, the Stock Option, to the extent vested immediately prior to the cessation of the Optionee’s Employment due to death, will remain exercisable until the earlier of (A) the first anniversary of the Optionee’s death or (B) the Final Exercise Date, and except to the extent previously exercised as permitted by this Section 3(c)(ii) will thereupon immediately terminate.

(iii)If the Optionee’s Employment is terminated by the Company and its subsidiaries in connection with an act or failure to act constituting Cause (as the Administrator, in its sole discretion, may determine), or such termination occurs in circumstances that in the determination of the Administrator would have entitled the Company and its subsidiaries to terminate the Optionee’s Employment for Cause, the Stock Option (whether

or not vested) will immediately terminate and be forfeited upon such termination.

4.Forfeiture; Recovery of Compensation.

(a)The Administrator may cancel, rescind, withhold or otherwise limit or restrict the Stock Option at any time if the Optionee is not in compliance with all applicable provisions of this Agreement and the Plan.

(b)By accepting the Stock Option, the Optionee expressly acknowledges and agrees that his or her rights, and those of any permitted transferee of the Stock Option, under the Stock Option to any Stock acquired under the Stock Option or proceeds from the disposition thereof, are subject to Section 6(a)(v) of the Plan (including any successor provision). Nothing in the preceding sentence shall be construed as limiting the general application of Section 8 of this Agreement.

5.Transfer of Stock Option. The Stock Option may not be transferred except as expressly permitted under Section 6(a)(iii) of the Plan.

6.Withholding. The Optionee shall be responsible for satisfying and paying all taxes arising from or due in connection with the Option, its exercise or a disposition of Shares acquired upon exercise of the Option. The Company shall have no liability or obligation related to the foregoing.

7.Effect on Service. Neither the grant of the Stock Option, nor the issuance of Shares upon exercise of the Stock Option, will give the Optionee any right to be retained in the employ or service of the Company or any of its Affiliates, affect the right of the Company or any of its Affiliates to discharge or discipline such Optionee at any time, or affect any right of such Optionee to terminate his or her Employment at any time.

8.Provisions of the Plan. This Agreement is subject in its entirety to the provisions of the Plan, which are incorporated herein by reference. A copy of the Plan as in effect on the Date of Grant has been furnished to the Optionee. By exercising all or any part of the Stock Option, the Optionee agrees to be bound by the terms of the Plan and this Agreement. In the event of any conflict between the terms of this Agreement and the Plan, the terms of the Plan shall control.

9.Acknowledgements. The Optionee acknowledges and agrees that (a) this Agreement may be executed in two or more counterparts, each of which shall be an original and all of which together shall constitute one and the same instrument, (b) this agreement may be executed and exchanged using facsimile, portable document format (PDF) or electronic signature, which, in each case, shall constitute an original signature for all purposes hereunder and (c) such signature by the Company will be binding against the Company and will create a legally binding agreement when this Agreement is countersigned by the Optionee.

The Stock Option evidenced by this Agreement is a non-statutory option (that is, an option that does not qualify as an incentive stock option under Section 422 of the Code) and is granted to the Optionee in connection with the Optionee’s employment by or service to the Company and its qualifying subsidiaries. For purposes of the immediately preceding sentence, “qualifying subsidiary” means a subsidiary of the Company as to which the Company has a “controlling interest” as described in Treas. Regs. §1.409A-1(b)(5)(iii)(E)(1).

[The remainder of this page is intentionally left blank]

IN WITNESS WHEREOF, the Company has caused this Agreement to be executed by its duly authorized officer.

ULTRAGENYX PHARMACEUTICAL Inc.

By: /s/ Emil Kakkis

Name: Emil Kakkis, M.D., Ph.D.

Title: Chief Executive Officer

Dated:

Acknowledged and Agreed:

By_______________________

EX-10.34

Exhibit 10.34

Name:

Number of Restricted Stock Units subject to Award:

Date of Grant:

Ultragenyx Pharmaceutical Inc.
2023 Incentive Plan

Restricted Stock Unit Agreement (Directors)

 This agreement (this “Agreement”) evidences an award (the “Award”) of restricted stock units (the “Restricted Stock Units”) granted by Ultragenyx Pharmaceutical Inc. (the “Company”) to the undersigned (the “Grantee”) pursuant to and subject to the terms of the Ultragenyx Pharmaceutical Inc. 2023 Incentive Plan (as amended from time to time, the “Plan”), which is incorporated herein by reference.

1. Grant of Restricted Stock Units. The Company grants to the Grantee on the date set forth above (the “Date of Grant”) an award consisting of the right to receive on the terms provided herein and in the Plan, one share of Stock with respect to each Restricted Stock Unit forming part of the Award, in each case, subject to adjustment pursuant to Section 7(b) of the Plan in respect of transactions occurring after the date hereof.

2. Meaning of Certain Terms. Except as otherwise defined herein, all capitalized terms used herein have the same meaning as in the Plan.

3. Vesting. Unless earlier terminated, forfeited, relinquished or expired, the Restricted Stock Units shall vest as follows:all of the underlying shares shall vest on the earlier of (i) the first anniversary of the Date of Grant or (ii) the date of the Company's annual meeting of stockholders first held after the Date of Grant.

4. Delivery of Stock. The Company shall deliver to the Grantee as soon as practicable upon the vesting of the Restricted Stock Units or any portion thereof, but in all events no later than March 15th of the year following the year in which such Restricted Stock Units vest, one share of Stock with respect to each such vested Restricted Stock Unit, subject to the terms of the Plan and this Agreement.

5. Dividends; Other Rights. The Award shall not be interpreted to bestow upon the Grantee any equity interest or ownership in the Company or any Affiliate prior to the date on which the Company delivers shares of Stock to the Grantee (if any). The Grantee is not entitled to vote any shares of Stock by reason of the granting of this Award or to receive or be credited with any dividends declared and payable on any share of Stock prior to the date on which any such share is delivered to the Grantee hereunder. The Grantee shall have the rights of a shareholder only as to those shares of Stock, if any, that are actually delivered under this Award.

6. Forfeiture; Recovery of Compensation.

(a) The Administrator may cancel, rescind, withhold or otherwise limit or restrict the Award at any time if the Grantee is not in compliance with all applicable provisions of this Agreement and the Plan.

(b) By accepting the Award the Grantee expressly acknowledges and agrees that his or her rights, and those of any permitted transferee of the Award, under the Award to any Stock acquired under the Award or proceeds from the disposition thereof, are subject to Section 6(a)(v) of the Plan (including any successor provision). Nothing in the preceding sentence shall be construed as limiting the general application of Section 10 of this Agreement.

7. Nontransferability. Neither the Award nor the Restricted Stock Units may be transferred except as expressly permitted under Section 6(a)(iii) of the Plan.

8. Certain Tax Matters.

 (a) The Grantee shall be responsible for satisfying and paying all taxes arising from or due in connection with the Restricted Stock Units or with the shares of Stock issued upon vesting of the Restricted Stock Units. The Company shall have no liability or obligation related to the foregoing.

 (b) The Grantee expressly acknowledges that because this Award consists of an unfunded and unsecured promise by the Company to deliver Stock in the future, subject to the terms hereof, it is not possible to make a so-called “83(b) election” with respect to the Award.

 9. Effect on Service. Neither the grant of the Award, nor the issuance of shares of Stock upon vesting of the Award, will give the Grantee any right to be retained in the employ or service of the Company or any of its Affiliates, affect the right of the Company or any of its Affiliates to discharge or discipline such Grantee at any time, or affect any right of such Grantee to terminate his or her Employment at any time.

 10. Provisions of the Plan. This Agreement is subject in its entirety to the provisions of the Plan, which are incorporated herein by reference. A copy of the Plan as in effect on the Date of Grant has been furnished to the Grantee. By accepting the Award, the Grantee agrees to be bound by the terms of the Plan and this Agreement. In the event of any conflict between the terms of this Agreement and the Plan, the terms of the Plan shall control.

11. Acknowledgments. The Grantee acknowledges and agrees that (a) this Agreement may be executed in two or more counterparts, each of which shall be an original and all of which together shall constitute one and the same instrument, (b) this agreement may be executed and exchanged using facsimile, portable document format (PDF) or electronic signature, which, in each case, shall constitute an original signature for all purposes hereunder and (c) such signature by the Company will be binding against the Company and will create a legally binding agreement when this Agreement is countersigned by the Grantee.

[The remainder of this page is intentionally left blank.]

IN WITNESS WHEREOF, the Company has caused this Agreement to be executed by its duly authorized officer.

ULTRAGENYX PHARMACEUTICAL Inc.

By: /s/ Emil Kakkis

Name: Emil Kakkis, M.D., Ph.D.

Title: Chief Executive Officer

Dated:

Acknowledged and Agreed:

By_______________________

EX-10.35

Exhibit 10.35

Name:

Number of Shares of Stock subject to Stock Option:

Price Per Share:

Date of Grant:

Vesting Start Date:

Ultragenyx Pharmaceutical Inc.
2023 Incentive Plan

Non-statutory Stock Option Agreement (Directors)

This agreement (this “Agreement”) evidences a stock option granted by Ultragenyx Pharmaceutical Inc. (the “Company”) to the undersigned (the “Optionee”) pursuant to and subject to the terms of the Ultragenyx Pharmaceutical Inc. 2023 Incentive Plan (as amended from time to time, the “Plan”),which is incorporated herein by reference.

1.Grant of Stock Option. The Company grants to the Optionee on the date set forth above (the “Date of Grant”) an option (the “Stock Option”) to purchase, on the terms provided herein and in the Plan, up to the number of shares of Stock set forth above (the “Shares”) with an exercise price per Share as set forth above, in each case subject to adjustment pursuant to Section 7(b) of the Plan in respect of transactions occurring after the date hereof.

2.Meaning of Certain Terms. Except as otherwise defined herein, all capitalized terms used herein have the same meaning as in the Plan. The following terms have the following meanings:

(a)“Beneficiary” means, in the event of the Optionee’s death, the beneficiary named in the written designation (in form acceptable to the Administrator) most recently filed with the Administrator by the Optionee prior to the Optionee’s death and not subsequently revoked, or, if there is no such designated beneficiary, the executor or administrator of the Optionee’s estate. An effective beneficiary designation will be treated as having been revoked only upon receipt by the Administrator, prior to the Optionee’s death, of an instrument of revocation in form acceptable to the Administrator.

(b)“Option Holder” means the Optionee or, if as of the relevant time the Stock Option has passed to a Beneficiary, the Beneficiary.

3.Vesting; Method of Exercise; Treatment of the Stock Option Upon Cessation of Employment.

(a)Vesting. As used herein with respect to the Stock Option or any portion thereof, the term “vest” means to become exercisable and the term “vested” as applied to any outstanding Stock Option means that the Stock Option is then exercisable, subject in each case to the terms of the Plan. Unless earlier terminated, forfeited, relinquished or expired, the Stock Option will vest as to 1/36th of the Shares initially subject to the Stock Option monthly, so that the Stock Option will fully vest on the third (3rd) anniversary of the Date of Grant. Notwithstanding the foregoing, Shares subject to

the Stock Option shall not vest on any vesting date unless the Optionee has remained in continuous Employment from the Date of Grant through such vesting date.

(b)Exercise of the Stock Option. No portion of the Stock Option may be exercised until such portion vests. Each election to exercise any vested portion of the Stock Option will be subject to the terms and conditions of the Plan and shall be in writing, signed by the Option Holder (or in such other form as is acceptable to the Administrator). Each such written exercise election must be received by the Company at its principal office or by such other party as the Administrator may prescribe and be accompanied by payment in full as provided in the Plan. The exercise price may be paid (i) by cash or check acceptable to the Administrator, (ii) to the extent permitted by the Administrator, through a broker-assisted cashless exercise program acceptable to the Administrator, (iii) by such other means, if any, as may be acceptable to the Administrator, or (iv) by any combination of the foregoing permissible forms of payment. In the event that the Stock Option is exercised by a person other than the Optionee, the Company will be under no obligation to deliver shares hereunder unless and until it is satisfied as to the authority of the Option Holder to exercise the Stock Option and compliance with applicable securities laws. The latest date on which the Stock Option or any portion thereof may be exercised will be the 10th anniversary of the Date of Grant (the “Final Exercise Date”); provided, however, if at such time the Optionee is prohibited by applicable law from exercising the Stock Option, the Final Exercise Date will be automatically extended to thirty (30) days following the date the Optionee is no longer prohibited from exercising the Stock Option. If the Stock Option is not exercised by the Final Exercise Date the Stock Option or any remaining portion thereof will thereupon immediately terminate.

(c)Treatment of the Stock Option Upon Cessation of Employment. If the Optionee’s Employment ceases, the Stock Option, to the extent not already vested will be immediately forfeited, and any vested portion of the Stock Option that is then outstanding will be treated as follows:

(i)Subject to clauses (ii) and (iii) below and Section 4 of this Agreement, the Stock Option, to the extent vested immediately prior to the cessation of the Optionee’s Employment, will remain exercisable until the earlier of (A) the date that is 24 months following the date of such cessation of Employment, or (B) the Final Exercise Date, and except to the extent previously exercised as permitted by this Section 3(c)(i) will thereupon immediately terminate.

(ii)Subject to clauses (iii) below and Section 4 of this Agreement, the Stock Option, to the extent vested immediately prior to the cessation of the Optionee’s Employment due to death, will remain exercisable until the earlier of (A) the first anniversary of the Optionee’s death or (B) the Final Exercise Date, and except to the extent previously exercised as permitted by this Section 3(c)(ii) will thereupon immediately terminate.

(iii)If the Optionee’s Employment is terminated by the Company and its subsidiaries in connection with an act or failure to act constituting Cause (as the Administrator, in its sole discretion, may determine), or such termination occurs in circumstances that in the determination of the Administrator would have entitled the Company and its subsidiaries to terminate the Optionee’s Employment for Cause, the Stock Option (whether

or not vested) will immediately terminate and be forfeited upon such termination.

4.Forfeiture; Recovery of Compensation.

(a)The Administrator may cancel, rescind, withhold or otherwise limit or restrict the Stock Option at any time if the Optionee is not in compliance with all applicable provisions of this Agreement and the Plan.

(b)By accepting the Stock Option, the Optionee expressly acknowledges and agrees that his or her rights, and those of any permitted transferee of the Stock Option, under the Stock Option to any Stock acquired under the Stock Option or proceeds from the disposition thereof, are subject to Section 6(a)(v) of the Plan (including any successor provision). Nothing in the preceding sentence shall be construed as limiting the general application of Section 8 of this Agreement.

5.Transfer of Stock Option. The Stock Option may not be transferred except as expressly permitted under Section 6(a)(iii) of the Plan.

6.Withholding. The Optionee shall be responsible for satisfying and paying all taxes arising from or due in connection with the Option, its exercise or a disposition of Shares acquired upon exercise of the Option. The Company shall have no liability or obligation related to the foregoing.

7.Effect on Service. Neither the grant of the Stock Option, nor the issuance of Shares upon exercise of the Stock Option, will give the Optionee any right to be retained in the employ or service of the Company or any of its Affiliates, affect the right of the Company or any of its Affiliates to discharge or discipline such Optionee at any time, or affect any right of such Optionee to terminate his or her Employment at any time.

8.Provisions of the Plan. This Agreement is subject in its entirety to the provisions of the Plan, which are incorporated herein by reference. A copy of the Plan as in effect on the Date of Grant has been furnished to the Optionee. By exercising all or any part of the Stock Option, the Optionee agrees to be bound by the terms of the Plan and this Agreement. In the event of any conflict between the terms of this Agreement and the Plan, the terms of the Plan shall control.

9.Acknowledgements. The Optionee acknowledges and agrees that (a) this Agreement may be executed in two or more counterparts, each of which shall be an original and all of which together shall constitute one and the same instrument, (b) this agreement may be executed and exchanged using facsimile, portable document format (PDF) or electronic signature, which, in each case, shall constitute an original signature for all purposes hereunder and (c) such signature by the Company will be binding against the Company and will create a legally binding agreement when this Agreement is countersigned by the Optionee.

The Stock Option evidenced by this Agreement is a non-statutory option (that is, an option that does not qualify as an incentive stock option under Section 422 of the Code) and is granted to the Optionee in connection with the Optionee’s employment by or service to the Company and its qualifying subsidiaries. For purposes of the immediately preceding sentence, “qualifying subsidiary” means a subsidiary of the Company as to which the Company has a “controlling interest” as described in Treas. Regs. §1.409A-1(b)(5)(iii)(E)(1).

[The remainder of this page is intentionally left blank]

IN WITNESS WHEREOF, the Company has caused this Agreement to be executed by its duly authorized officer.

ULTRAGENYX PHARMACEUTICAL Inc.

By: /s/ Emil Kakkis

Name: Emil Kakkis, M.D., Ph.D.

Title: Chief Executive Officer

Dated:

Acknowledged and Agreed:

By_______________________

EX-10.36

Exhibit 10.36

Name:

Number of Restricted Stock Units subject to Award:

Date of Grant:

Ultragenyx Pharmaceutical Inc.
2023 Incentive Plan

Restricted Stock Unit Agreement (Directors)

 This agreement (this “Agreement”) evidences an award (the “Award”) of restricted stock units (the “Restricted Stock Units”) granted by Ultragenyx Pharmaceutical Inc. (the “Company”) to the undersigned (the “Grantee”) pursuant to and subject to the terms of the Ultragenyx Pharmaceutical Inc. 2023 Incentive Plan (as amended from time to time, the “Plan”), which is incorporated herein by reference.

1. Grant of Restricted Stock Units. The Company grants to the Grantee on the date set forth above (the “Date of Grant”) an award consisting of the right to receive on the terms provided herein and in the Plan, one share of Stock with respect to each Restricted Stock Unit forming part of the Award, in each case, subject to adjustment pursuant to Section 7(b) of the Plan in respect of transactions occurring after the date hereof.

2. Meaning of Certain Terms. Except as otherwise defined herein, all capitalized terms used herein have the same meaning as in the Plan.

3. Vesting. Unless earlier terminated, forfeited, relinquished or expired, the Restricted Stock Units shall vest as follows:1/3 of the underlying shares shall vest on each anniversary of the Date of Grant so that the Restricted Stock Units will fully vest on the third (3rd) anniversary of the Date of Grant.

4. Delivery of Stock. The Company shall deliver to the Grantee as soon as practicable upon the vesting of the Restricted Stock Units or any portion thereof, but in all events no later than March 15th of the year following the year in which such Restricted Stock Units vest, one share of Stock with respect to each such vested Restricted Stock Unit, subject to the terms of the Plan and this Agreement.

5. Dividends; Other Rights. The Award shall not be interpreted to bestow upon the Grantee any equity interest or ownership in the Company or any Affiliate prior to the date on which the Company delivers shares of Stock to the Grantee (if any). The Grantee is not entitled to vote any shares of Stock by reason of the granting of this Award or to receive or be credited with any dividends declared and payable on any share of Stock prior to the date on which any such share is delivered to the Grantee hereunder. The Grantee shall have the rights of a shareholder only as to those shares of Stock, if any, that are actually delivered under this Award.

6. Forfeiture; Recovery of Compensation.

(a) The Administrator may cancel, rescind, withhold or otherwise limit or restrict the Award at any time if the Grantee is not in compliance with all applicable provisions of this Agreement and the Plan.

(b) By accepting the Award the Grantee expressly acknowledges and agrees that his or her rights, and those of any permitted transferee of the Award, under the Award to any Stock acquired under the Award or proceeds from the disposition thereof, are subject to Section 6(a)(v) of the Plan (including any successor provision). Nothing in the preceding sentence shall be construed as limiting the general application of Section 10 of this Agreement.

7. Nontransferability. Neither the Award nor the Restricted Stock Units may be transferred except as expressly permitted under Section 6(a)(iii) of the Plan.

8. Certain Tax Matters.

 (a) The Grantee shall be responsible for satisfying and paying all taxes arising from or due in connection with the Restricted Stock Units or with the shares of Stock issued upon vesting of the Restricted Stock Units. The Company shall have no liability or obligation related to the foregoing.

 (b) The Grantee expressly acknowledges that because this Award consists of an unfunded and unsecured promise by the Company to deliver Stock in the future, subject to the terms hereof, it is not possible to make a so-called “83(b) election” with respect to the Award.

 9. Effect on Service. Neither the grant of the Award, nor the issuance of shares of Stock upon vesting of the Award, will give the Grantee any right to be retained in the employ or service of the Company or any of its Affiliates, affect the right of the Company or any of its Affiliates to discharge or discipline such Grantee at any time, or affect any right of such Grantee to terminate his or her Employment at any time.

 10. Provisions of the Plan. This Agreement is subject in its entirety to the provisions of the Plan, which are incorporated herein by reference. A copy of the Plan as in effect on the Date of Grant has been furnished to the Grantee. By accepting the Award, the Grantee agrees to be bound by the terms of the Plan and this Agreement. In the event of any conflict between the terms of this Agreement and the Plan, the terms of the Plan shall control.

11. Acknowledgments. The Grantee acknowledges and agrees that (a) this Agreement may be executed in two or more counterparts, each of which shall be an original and all of which together shall constitute one and the same instrument, (b) this agreement may be executed and exchanged using facsimile, portable document format (PDF) or electronic signature, which, in each case, shall constitute an original signature for all purposes hereunder and (c) such signature by the Company will be binding against the Company and will create a legally binding agreement when this Agreement is countersigned by the Grantee.

[The remainder of this page is intentionally left blank.]

IN WITNESS WHEREOF, the Company has caused this Agreement to be executed by its duly authorized officer.

ULTRAGENYX PHARMACEUTICAL Inc.

By: /s/ Emil Kakkis

Name: Emil Kakkis, M.D., Ph.D.

Title: Chief Executive Officer

Dated:

Acknowledged and Agreed:

By_______________________

EX-21.1

Exhibit 21.1

Significant Subsidiaries of Ultragenyx Pharmaceutical Inc.

Name of Subsidiary	Jurisdiction of Incorporation
Ultragenyx Holdco LLC	Delaware
Rare Delaware Inc.	Delaware
GeneTx Biotherapeutics LLC	Delaware
Ultragenyx UK Ltd	United Kingdom
Amlogenyx Inc.	Delaware
Ultragenyx Europe GmbH	Switzerland
Ultragenyx Germany GmbH	Germany
Ultragenyx Brasil Farmacêutica Ltda	Brazil
Ultragenyx Argentina SRL	Argentina
Ultragenyx Netherlands B.V.	Netherlands
Ultragenyx France SAS	France
Ultragenyx Colombia SAS	Colombia
Ultragenyx Canada Inc.	Canada
Ultragenyx México, S. de R.L. de C.V.	Mexico
Ultragenyx Japan K.K.	Japan
Ultragenyx Chile Limitada	Chile

EX-23.1

Exhibit 23.1

CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM

We consent to the incorporation by reference in the following Registration Statements:

(1) Registration Statements (Form S-8 Nos. 333-194773, 333-201843, 333-209729, 333-216110, 333-223124, 333-229746, 333-236428, 333-253007, 333-262751, 333-269840, and 333-272518) pertaining to the 2011 Equity Incentive Plan, as amended, 2014 Incentive Plan, as amended, 2014 Employee Stock Purchase Plan, as amended and restated, 2023 Incentive Plan, and Employee Inducement Plan, as amended of Ultragenyx Pharmaceutical Inc.,

(2) Registration Statement (Form S-8 No. 333-221381) pertaining to the Dimension Therapeutics, Inc. 2015 Stock Option and Incentive Plan and the Dimension Therapeutics, Inc. 2013 Stock Plan, both as assumed by Ultragenyx Pharmaceutical Inc., and

(3) Registration Statement (Form S-3 No. 333-253008) and related Prospectus of Ultragenyx Pharmaceutical Inc. for the registration of common stock, preferred stock, debt securities, warrants and units;

of our reports dated February 21, 2024, with respect to the consolidated financial statements of Ultragenyx Pharmaceutical Inc. and the effectiveness of internal control over financial reporting of Ultragenyx Pharmaceutical Inc. included in this Annual Report (Form 10-K) of Ultragenyx Pharmaceutical Inc. for the year ended December 31, 2023.

/s/ Ernst & Young LLP

San Mateo, California

February 21, 2024

EX-31.1

Exhibit 31.1

CERTIFICATION PURSUANT TO SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002

I, Emil D. Kakkis, certify that:

1.I have reviewed this Annual Report on Form 10-K of Ultragenyx Pharmaceutical Inc.;

2.Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;

3.Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;

4.I am responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:

a)Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;

b)Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;

c)Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and

d)Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and

5.I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):

a)All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and

b)Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting.

Dated: February 21, 2024	/s/ Emil D. Kakkis
	Emil D. Kakkis, M.D., Ph.D.
	President and Chief Executive Officer
	(Principal Executive Officer)

EX-31.2

Exhibit 31.2

CERTIFICATION PURSUANT TO SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002

I, Howard Horn, certify that:

1.I have reviewed this Annual Report on Form 10-K of Ultragenyx Pharmaceutical Inc.;

2.Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;

3.Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;

4.I am responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:

1.Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;

2.Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;

3.Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and

4.Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and

5.I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):

1.All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and

2.Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting.

Dated: February 21, 2024	/s/ Howard Horn
	Howard Horn
	Executive Vice President, Chief Financial Officer, Corporate Strategy (Principal Financial Officer)

EX-32.1

Exhibit 32.1

CERTIFICATION PURSUANT TO SECTION 906 OF

THE SARBANES-OXLEY ACT OF 2002 (18 U.S.C. SECTION 1350)

In connection with the accompanying Annual Report of Ultragenyx Pharmaceutical Inc. (the “Company”) on Form 10-K for the year ended December 31, 2023 (the “Report”), I, Emil D. Kakkis, M.D., Ph.D., as President and Chief Executive Officer of the Company, and Howard Horn, as Executive Vice President, Chief Financial Officer, Corporate Strategy of the Company, certify, pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, that:

(1) The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and

(2) The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.

Dated: February 21, 2024	/s/ Emil D. Kakkis
	Emil D. Kakkis, M.D., Ph.D.
	President and Chief Executive Officer (Principal Executive Officer)

Dated: February 21, 2024	/s/ Howard Horn
	Howard Horn
	Executive Vice President, Chief Financial Officer, Corporate Strategy (Principal Financial Officer)

EX-97.1

Exhibit 97.1

ULTRAGENYX PHARMACEUTICAL INC.

CLAWBACK POLICY

This Clawback Policy (this “Policy”) has been adopted by the Board of Directors (the “Board”) of Ultragenyx Pharmaceutical Inc. (the “Company”) effective October 2, 2023 (the “Effective Date”) and replaces the Company’s Clawback Policy dated December 13, 2017 in its entirety. This Policy is administered by the Compensation Committee (the “Committee”) of the Board, subject to ratification by the independent members of the Board with respect to application of this Policy to the Company’s Chief Executive Officer, and is intended to comply with, and as applicable to be administered and interpreted consistent with, and subject to the exceptions set forth in, Listing Rule 5608 adopted by the Nasdaq Stock Market to implement Rule 10D-1 under the Securities Exchange Act of 1934, as amended (collectively, “Rule 10D-1”).

Mandatory Recoupment

In the event the Company is required to prepare an accounting restatement of the Company’s financial statements (including any such correction that is material to the previously issued financial statements, or that would result in a material misstatement if the error were corrected in the current period or left uncorrected in the current period) due to material non-compliance with any financial reporting requirement under the federal securities laws (as applicable, a “Restatement”), the Company will recover on a reasonably prompt basis the amount of any Incentive-Based Compensation Received by a Covered Executive during the Recovery Period that exceeds the amount that otherwise would have been Received had it been determined based on the restated financial statements.

If the Committee determines the amount of Incentive-Based Compensation Received by a Covered Executive during a Recovery Period exceeds the amount that would have been Received if determined or calculated based on the Company’s restated financial results, such excess amount of Incentive-Based Compensation shall be subject to recoupment by the Company pursuant to this Policy. For Incentive-Based Compensation based on stock price or total shareholder return, where the amount of erroneously awarded compensation is not subject to mathematical recalculation directly from the information in an accounting restatement, the Committee will determine the amount based on a reasonable estimate of the effect of the accounting restatement on the relevant stock price or total shareholder return. In all cases, the calculation of the excess amount of Incentive-Based Compensation to be recovered will be determined on a pre-tax basis. The Company will maintain and will provide to The Nasdaq Stock Market documentation of all determinations and actions taken in complying with the Mandatory Recoupment provisions of this Policy.

Discretionary Recoupment

In addition to the mandatory recoupment (required under Rule 10D-1) set forth above, in the event that the Committee determines, in its sole discretion, that an act or omission of a Covered Executive contributed to the circumstances requiring the Restatement and that such act or omission involved Fraud or Intentional Misconduct, then the Committee may recover all (not just the excess amount) Incentive-Based Compensation as well as Other Incentive Compensation, in each case, Received by such Covered Executive.

Definitions

For purposes of this Policy:

•“Incentive-Based Compensation” means any compensation granted, earned or vested based in whole or in part on the Company’s attainment of a financial reporting measure that was Received

by a person (i) on or after the Effective Date and after the person began service as a Covered Executive, and (ii) who served as a Covered Executive at any time during the performance period for the Incentive-Based Compensation. A financial reporting measure is (A) any measure that is determined and presented in accordance with the accounting principles used in preparing the Company’s financial statements and any measure derived wholly or in part from such a measure, and (B) any measure based in whole or in part on the Company’s stock price or total shareholder return.

•“Covered Executive” means any “executive officer” of the Company as defined under Rule 10D-1.

•“Fraud or Intentional Misconduct” includes reckless conduct (including any highly unreasonable act or omission, involving not merely simple, or even inexcusable negligence, but an extreme departure from the standards of ordinary care, and that is either known to the Covered Executive or is so obvious the Covered Executive must have been aware of it), but is not intended to include (i) negligent conduct or grossly negligent conduct not arising to such standard or (ii) conduct in good faith and in a manner the Covered Executive reasonably believed to be in, or not opposed to, the best interests of the Company (including the Covered Executive’s good faith scientific or medical judgments).

•“Other Incentive Compensation” means any incentive compensation (other than Incentive-Based Compensation), including, but not limited to, service- or time-based equity awards and bonuses and performance-based equity awards and bonuses that are not based on a financial reporting measure, that was Received by a person (i) on or after the Effective Date and after the person began service as a Covered Executive, and (ii) who served as a Covered Executive at any time during the vesting or service period or performance period, as applicable, for the Other Incentive Compensation.

•Incentive-Based Compensation is deemed to be “Received” in the fiscal period during which the relevant financial reporting measure is attained, regardless of when the compensation is actually paid or awarded. Other Incentive Compensation is deemed to be “Received” in the fiscal period during which any applicable performance measure is attained or any service- or time-based requirement is satisfied, regardless of when the compensation is actually paid or awarded.

•“Recovery Period” means the three completed fiscal years immediately preceding the date that the Company is required to prepare the accounting restatement described in this Policy, as determined pursuant to Rule 10D-1, and any transition period of less than nine months that is within or immediately following such three fiscal years.

Recovery

The Company may effect any recovery pursuant to this Policy by requiring payment of such amount(s) to the Company, by set-off, by reducing future compensation, or by such other means or combination of means as the Committee determines to be appropriate. The Company need not recover the excess amount of Incentive-Based Compensation if and to the extent that the Committee determines that such recovery is impracticable, subject to and in accordance with any applicable exceptions under the Nasdaq Stock Market listing rules and not required under Rule 10D-1, including if the Committee determines that the direct expense paid to a third party to assist in enforcing this Policy would exceed the amount to be recovered after making a reasonable attempt to recover such amounts. The Company is authorized to take appropriate steps to implement this Policy with respect to Incentive-Based Compensation and Other Incentive Compensation arrangements with Covered Executives. Any determinations made by the Committee under this Policy shall be final and binding on all affected individuals.

2

Additional Recoupment Rights

Any right of recoupment or recovery pursuant to this Policy is in addition to, and not in lieu of, any other remedies or rights of recoupment that may be available to the Company pursuant to the terms of any other policy, any employment agreement or plan or award terms, and any other legal remedies available to the Company; provided that the Company shall not recoup amounts pursuant to such other policy, terms or remedies to the extent it is recovered pursuant to this Policy. The Company shall not indemnify any Covered Executive against the loss of any Incentive-Based Compensation or Other Incentive Compensation pursuant to this Policy.

3

XML

Document and Entity Information - USD ($)
$ in Billions

12 Months Ended

Dec. 31, 2023

Feb. 15, 2024

Jun. 30, 2023

Cover [Abstract]

Document Type

10-K

Amendment Flag

false

Document Period End Date

Dec. 31, 2023

Document Fiscal Year Focus

2023

Document Fiscal Period Focus

FY

Trading Symbol

RARE

Entity Registrant Name

Ultragenyx Pharmaceutical Inc.

Entity Central Index Key

0001515673

Current Fiscal Year End Date

--12-31

Entity Well-known Seasoned Issuer

Yes

Entity Current Reporting Status

Yes

Entity Voluntary Filers

No

Entity Interactive Data Current

Yes

Entity Filer Category

Large Accelerated Filer

Entity Small Business

false

Entity Emerging Growth Company

false

ICFR Auditor Attestation Flag

true

Document Financial Statement Error Correction [Flag]

false

Entity Shell Company

false

Entity Common Stock, Shares Outstanding

82,335,687

Entity Public Float

$ 3.1

Security Exchange Name

NASDAQ

Title of 12(b) Security

Common Stock, $0.001 par value

Entity File Number

001-36276

Entity Incorporation, State or Country Code

DE

Entity Tax Identification Number

27-2546083

Entity Address, Address Line One

60 Leveroni Court

Entity Address, City or Town

Novato

Entity Address, State or Province

CA

Entity Address, Postal Zip Code

94949

City Area Code

415

Local Phone Number

483-8800

Document Annual Report

true

Document Transition Report

false

Documents Incorporated by Reference

DOCUMENTS INCORPORATED BY REFERENCE

Portions of the registrant’s definitive proxy statement relating to its 2024 Annual Meeting of Stockholders, to be held on or about June 18, 2024, are incorporated by reference into Part III of this Annual Report on Form 10-K where indicated. Such proxy statement will be filed with the U.S. Securities and Exchange Commission within 120 days after the end of the fiscal year to which this report relates.

Auditor Firm ID

42

Auditor Name

Ernst & Young LLP

Auditor Location

San Mateo, California

XML

CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Current assets:
Cash and cash equivalents	$ 213,584	$ 132,944
Marketable debt securities	363,625	614,818
Accounts receivable, net	73,390	40,445
Inventory	33,969	26,766
Other assets	47,616	68,926
Total current assets	732,184	883,899
Property, plant, and equipment, net	290,566	259,726
Marketable debt securities	199,901	148,970
Intangible assets, net	166,271	160,105
Goodwill	44,406	44,406
Other assets	57,685	48,338
Total assets	1,491,013	1,545,444
Current liabilities:
Accounts payable	42,114	43,274
Accrued liabilities	196,486	204,678
Contract liabilities	0	1,479
Lease liabilities	12,595	11,779
Liabilities for sales of future royalties	29,242	0
Total current liabilities	280,437	261,210
Lease liabilities	30,574	19,814
Deferred tax liabilities	30,058	31,667
Liabilities for sales of future royalties	862,325	875,439
Other liabilities	12,205	4,820
Total liabilities	1,215,599	1,192,950
Commitments and contingencies (Notes 9 and 15)
Stockholders’ equity:
Preferred stock, par value of $0.001 per share - 25,000,000 shares authorized; nil outstanding in 2023 and in 2022	0	0
Common stock, par value of $0.001 per share - 250,000,000 shares authorized;outstanding - 82,315,590 in 2023 and 70,197,297 in 2022	82	70
Treasury stock, at cost, 9,559 in 2023 and nil in 2022	(432)	0
Deferred compensation obligation	432	0
Additional paid-in capital	3,662,346	3,140,019
Accumulated other comprehensive income (loss)	647	(6,573)
Accumulated deficit	(3,387,661)	(2,781,022)
Total stockholders’ equity	275,414	352,494
Total liabilities and stockholders’ equity	$ 1,491,013	$ 1,545,444

XML

CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Dec. 31, 2023	Dec. 31, 2022
Statement of Financial Position [Abstract]
Preferred stock, par value	$ 0.001	$ 0.001
Preferred stock, shares authorized	25,000,000	25,000,000
Preferred stock, shares outstanding	0	0
Common stock, par value	$ 0.001	$ 0.001
Common stock, shares authorized	250,000,000	250,000,000
Common stock, shares outstanding	82,315,590	70,197,297
Treasury stock , shares	9,559	0

XML

CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Revenues:
Total revenues	$ 434,249	$ 363,329	$ 351,406
Operating expenses:
Cost of sales	45,209	28,320	16,008
Research and development	648,449	705,789	497,153
Selling, general and administrative	309,799	278,139	219,982
Total operating expenses	1,003,457	1,012,248	733,143
Loss from operations	(569,208)	(648,919)	(381,737)
Interest income	26,688	11,074	1,928
Change in fair value of equity investments	397	(19,299)	(42,063)
Non-cash interest expense on liabilities for sales of future royalties	(66,004)	(43,015)	(29,422)
Other expense	(337)	(1,566)	(1,687)
Loss before income taxes	(608,464)	(701,725)	(452,981)
Benefit from (provision for) income taxes	1,825	(5,696)	(1,044)
Net loss	$ (606,639)	$ (707,421)	$ (454,025)
Net loss per share, basic	$ (8.25)	$ (10.12)	$ (6.7)
Net loss per share, diluted	$ (8.25)	$ (10.12)	$ (6.7)
Shares used in computing net loss per share, Basic	73,543,862	69,914,225	67,795,540
Shares used in computing net loss per share, Diluted	73,543,862	69,914,225	67,795,540
Product sales
Revenues:
Total revenues	$ 180,413	$ 118,927	$ 77,017
Royalty revenue
Revenues:
Total revenues	182,652	21,692	17,951
Collaboration and license
Revenues:
Total revenues	$ 71,184	$ 222,710	$ 256,438

XML

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Statement of Comprehensive Income [Abstract]
Net loss	$ (606,639)	$ (707,421)	$ (454,025)
Other comprehensive income (loss):
Foreign currency translation adjustments	239	(724)	(550)
Unrealized gain (loss) on available-for-sale securities	6,981	(4,445)	(1,543)
Other comprehensive income (loss):	7,220	(5,169)	(2,093)
Total comprehensive loss	$ (599,419)	$ (712,590)	$ (456,118)

XML

CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($) $ in Thousands	Total	Common Stock	Additional Paid-in Capital	Accumulated Other Comprehensive Income (Loss)	Accumulated Deficit	Treasury Stock	Deferred Compensation Obligation
Beginning balance at Dec. 31, 2020	$ 1,154,375	$ 67	$ 2,773,195	$ 689	$ (1,619,576)
Beginning balance, shares at Dec. 31, 2020		66,818,520
Issuance of common stock in connection with at-the-market offering, net of issuance costs	78,943	$ 1	78,942
Issuance of common stock in connection with at-the-market offering, net of issuance costs, shares		1,050,372
Stock-based compensation	105,260		105,260
Issuance of common stock under equity plan awards, net of tax	40,101	$ 1	40,100
Issuance of common stock under equity plan awards, net of tax, shares		1,476,106
Other comprehensive income (loss)	(2,093)			(2,093)
Net loss	(454,025)				(454,025)
Ending balance at Dec. 31, 2021	922,561	$ 69	2,997,497	(1,404)	(2,073,601)
Ending balance, shares at Dec. 31, 2021		69,344,998
Stock-based compensation	131,710		131,710
Issuance of common stock under equity plan awards, net of tax	10,813	$ 1	10,812
Issuance of common stock under equity plan awards, net of tax, shares		852,299
Other comprehensive income (loss)	(5,169)			(5,169)
Net loss	(707,421)				(707,421)
Ending balance at Dec. 31, 2022	$ 352,494	$ 70	3,140,019	(6,573)	(2,781,022)
Ending balance, shares at Dec. 31, 2022	70,197,297	70,197,297
Issuance of common stock and pre-funded warrants in connection with underwritten public offering, net of issuance costs	$ 326,456	$ 10	326,446
Issuance of common stock in connection with at-the-market offering, net of issuance costs	$ 53,299	$ 1	53,298
Issuance of common stock and pre-funded warrants in connection with underwritten public offering, net of issuance costs,shares		9,833,334
Issuance of common stock in connection with at-the-market offering, net of issuance costs, shares	1,175,584	1,175,584
Stock-based compensation	$ 134,169		134,169
Issuance of common stock upon exercise of warrants and under equity plan awards, net of tax	8,415	$ 1	8,414
Issuance of common stock upon exercise of warrants and under equity plan awards, net of tax, shares		1,109,375
Deferred compensation						$ (432)	$ 432
Other comprehensive income (loss)	7,220			7,220
Net loss	(606,639)				(606,639)
Ending balance at Dec. 31, 2023	$ 275,414	$ 82	$ 3,662,346	$ 647	$ (3,387,661)	$ (432)	$ 432
Ending balance, shares at Dec. 31, 2023	82,315,590	82,315,590

XML

CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Operating activities:
Net loss	$ (606,639)	$ (707,421)	$ (454,025)
Adjustments to reconcile net loss to net cash used in operating activities:
Stock-based compensation	135,227	130,377	104,952
Acquired in-process research and development	0	75,033	0
Amortization of premium (discount) on marketable debt securities, net	(12,842)	2,699	6,606
Depreciation and amortization	26,006	18,220	13,239
Change in fair value of equity investments	(397)	19,299	42,063
Non-cash collaboration royalty revenue	(69,364)	(21,692)	(17,951)
Non-cash interest expense on liabilities for sales of future royalties	66,004	43,015	29,422
Other	2,300	(230)	235
Changes in operating assets and liabilities:
Accounts receivable	(22,778)	(12,068)	(5,432)
Inventory	(6,930)	(9,701)	(3,117)
Other assets	15,325	3,798	(29,508)
Accounts payable, accrued, and other liabilities	2,380	87,442	32,313
Contract liabilities, net	(1,479)	(7,597)	(57,492)
Deferred tax liabilities	(1,619)	(1,639)	0
Net cash used in operating activities	(474,806)	(380,465)	(338,695)
Investing activities:
Purchase of property, plant, and equipment	(44,267)	(116,123)	(73,093)
Acquisition, net of cash acquired	0	(75,025)	0
Purchase of marketable debt securities	(526,382)	(614,735)	(1,012,187)
Proceeds from sale of marketable debt securities	50,672	84,275	92,896
Proceeds from sale of equity investments	0	10,094	79,843
Proceeds from maturities of marketable debt securities	695,525	450,706	718,111
Payment for intangible asset	(2,500)	(30,000)	0
Other	(5,048)	(844)	(942)
Net cash provided by (used in) investing activities	168,000	(291,652)	(195,372)
Financing activities:
Proceeds from the sale of future royalties, net	0	490,950	0
Proceeds from the issuance of common stock and pre-funded warrants in connection with underwritten public offerings, net of issuance costs	326,456	0	0
Proceeds from the issuance of common stock in connection with at-the-market offering, net of issuances costs	53,299	0	78,943
Proceeds from the issuance of common stock from exercise of warrants and equity plan awards, net	8,415	10,813	40,101
Other	(28)	(555)	(492)
Net cash provided by financing activities	388,142	501,208	118,552
Effect of exchange rate changes on cash	462	(1,075)	(1,194)
Net increase (decrease) in cash, cash equivalents, and restricted cash	81,798	(171,984)	(416,709)
Cash, cash equivalents, and restricted cash at beginning of year	137,601	309,585	726,294
Cash, cash equivalents, and restricted cash at end of year	219,399	137,601	309,585
Supplemental disclosures of non-cash investing and financing information:
Acquired lease liabilities arising from obtaining right-of-use assets and property, plant, and equipment	22,162	1,168	3,142
Costs of property and equipment included in accounts payable, accrued, and other liabilities	1,577	17,963	18,993
Non-cash interest expense on liabilities for sales of future royalties capitalized during the year into ending property, plant and equipment	$ 9,431	$ 11,380	$ 4,650

XML

Pay vs Performance Disclosure - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Pay vs Performance Disclosure
Net Income (Loss)	$ (606,639)	$ (707,421)	$ (454,025)

XML

Insider Trading Arrangements

3 Months Ended

Dec. 31, 2023

shares

Trading Arrangements, by Individual

Material Terms of Trading Arrangement

On November 10, 2023, Corsee Sanders, Ph.D., a member of the Company’s Board of Directors, adopted a trading arrangement intended to satisfy the affirmative defense of Rule 10b5-1(c), to sell up to 2,322 shares of the Company’s common stock through July 12, 2024, subject to certain conditions.

On December 7, 2023, Matthew Fust, a member of the Company’s Board of Directors, adopted a trading arrangement intended to satisfy the affirmative defense of Rule 10b5-1(c), to sell up to 12,195 shares of the Company’s common stock through December 6, 2024, subject to certain conditions.

Corsee Sanders [Member]

Trading Arrangements, by Individual

Name

Corsee Sanders

Title

member of the Company’s Board of Directors

Rule 10b5-1 Arrangement Adopted

true

Adoption Date

November 10, 2023

Aggregate Available

2,322

Matthew Fust [Member]

Trading Arrangements, by Individual

Name

Matthew Fust

Title

member of the Company’s Board of Directors

Rule 10b5-1 Arrangement Adopted

true

Adoption Date

December 7, 2023

Aggregate Available

12,195

XML

Organization and Basis of Presentation

12 Months Ended

Dec. 31, 2023

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Organization and Basis of Presentation

1.Organization and Basis of Presentation

Ultragenyx Pharmaceutical Inc., or the Company, is a biopharmaceutical company incorporated in Delaware.

The Company is focused on the identification, acquisition, development, and commercialization of novel products for the treatment of serious rare and ultrarare genetic diseases. The Company operates as one reportable segment and has four commercially approved products.

Crysvita® (burosumab) is approved in the United States, or U.S., the European Union, or EU, and certain other regions for the treatment of X-linked hypophosphatemia, or XLH, in adult and pediatric patients one year of age and older. Crysvita is also approved in the U.S. and certain other regions for the treatment of fibroblast growth factor 23, or FGF23-related hypophosphatemia in tumor-induced osteomalacia, or TIO, associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older.

Mepsevii® (vestronidase alfa) is approved in the U.S., the EU and certain other regions, as the first medicine for the treatment of children and adults with mucopolysaccharidosis VII, or MPS VII, also known as Sly syndrome.

Dojolvi® (triheptanoin) is approved in the U.S. and certain other regions for the treatment of pediatric and adult patients severely affected by long-chain fatty acid oxidation disorders, or LC-FAOD.

Evkeeza® (evinacumab) is approved in the U.S. and the European Economic Area, or EEA, for the treatment of homozygous familial hypercholesterolemia, or HoFH. The Company has exclusive rights to commercialize Evkeeza® (evinacumab) outside of the U.S.

In addition to the approved products, the Company has the following ongoing clinical development programs:

•UX111 (formerly ABO-102) is an AAV9 gene therapy product candidate for the treatment of patients with Sanfilippo syndrome type A, or MPS IIIA, a rare lysosomal storage disease;

•DTX401 is an adeno-associated virus 8, or AAV8, gene therapy product candidate for the treatment of patients with glycogen storage disease type Ia, or GSDIa;

•DTX301 is an AAV8 gene therapy product candidate in development for the treatment of patients with ornithine transcarbamylase, or OTC deficiency, the most common urea cycle disorder;

•UX143 (setrusumab), which is subject to the Company’s collaboration agreement with Mereo BioPharma 3, or Mereo, is a fully human monoclonal antibody that inhibits sclerostin, a protein that acts on a key bone-signaling pathway and inhibits the activity of bone-forming cells for the treatment of patients with osteogenesis imperfect, or OI;

•GTX-102 is an antisense oligonucleotide, or ASO for the treatment of Angelman syndrome, a debilitating and rare neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene.; and

•UX701 is an adeno-associated virus 9, or AAV9, gene therapy designed to deliver stable expression of a truncated version of the ATP7B copper transporter following a single intravenous infusion to improve copper distribution and excretion from the body and reverse pathological findings of Wilson liver disease;

The Company has sustained operating losses and expects such annual losses to continue over the next several years. The Company’s ultimate success depends on the outcome of its research and development and commercialization activities. Through December 31, 2023, the Company has relied primarily on its sale of equity securities, its revenues from commercial products, its sale of future royalties, and strategic collaboration arrangements to finance its operations. The Company may need to raise additional capital to fully implement its business plans through the issuance of equity, borrowings, or strategic alliances with partner companies. However, if such financing is not available at adequate levels, the Company would need to reevaluate its operating plans.

XML

Summary of Significant Accounting Policies

12 Months Ended

Dec. 31, 2023

Accounting Policies [Abstract]

Summary of Significant Accounting Policies

2.Summary of Significant Accounting Policies

Basis of Consolidation

The Consolidated Financial Statements include the accounts of Ultragenyx Pharmaceutical Inc. and its wholly owned subsidiaries. All intercompany balances and transactions have been eliminated.

Use of Estimates

The accompanying Consolidated Financial Statements have been prepared in accordance with U.S. generally accepted accounting principles, or GAAP. The preparation of the Consolidated Financial Statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, disclosure of contingent liabilities and the reported amounts of expenses in the Consolidated Financial Statements and the accompanying notes. On an ongoing basis, management evaluates its estimates, including those related to clinical trial accruals, fair value of assets and liabilities, income taxes, stock-based compensation, revenue recognition, and the liabilities for sales of future royalties. Management bases its estimates on historical experience and on various other market-specific and relevant assumptions that management believes to be reasonable under the circumstances. Actual results could differ from those estimates.

Cash, Cash Equivalents, and Restricted Cash

The Company considers all highly liquid investments with original maturities of three months or less from the date of purchase to be cash equivalents. Cash equivalents consist primarily of amounts invested in money market accounts.

Restricted cash primarily consists of money market accounts used as collateral for the Company’s obligations under its facility leases and the gene therapy building construction project.

The following table provides a reconciliation of cash, cash equivalents, and restricted cash reported within the Consolidated Balance Sheets that sum to the total of the same such amounts shown in the Consolidated Statements of Cash Flows (in thousands):

	December 31,
	2023		2022		2021
Cash and cash equivalents	$	213,584	$	132,944	$	307,584
Restricted cash included in other current assets		2,008		862		—
Restricted cash included in other non-current assets		3,807		3,795		2,001
Total cash, cash equivalents, and restricted cash     shown in the statements of cash flows	$	219,399	$	137,601	$	309,585

Marketable Debt Securities

All marketable debt securities have been classified as “available-for-sale” and are carried at estimated fair value as determined based upon quoted market prices or pricing models for similar securities. Management determines the appropriate classification of its investments at the time of purchase and reevaluates such designation as of each balance sheet date. Investments with a maturity of one year or less from the balance sheet date are reported as current marketable debt securities and investments with a maturity of greater than one year from the balance sheet date are reported as non-current marketable debt securities. Unrealized gains and losses are excluded from earnings and are reported as a component of comprehensive loss. Realized gains and losses and declines in fair value judged to be other than temporary, if any, on available-for-sale securities are included in other income (expense). The cost of securities sold is based on the specific-identification method. Interest on investments is included in interest income.

Equity Investments

The Company records investments in equity securities, other than equity method investments, at fair market value, if the fair value is readily determinable. Equity securities with no readily determinable fair values are recorded using the measurement alternative of cost adjusted for observable price changes in orderly transactions for identical or similar investments of the same issuer less impairment, if any. Investments in equity securities are recorded in Equity investments on the Company's Consolidated Balance Sheets. Unrealized gains and losses are reported in Change in fair value of equity investments on the Company’s Consolidated Statements of Operations. The Company regularly reviews its non-marketable equity securities for indicators of impairment.

Concentration of Credit Risk, Credit Losses, and Other Risks and Uncertainties

Financial instruments that potentially subject the Company to a concentration of credit risk consist of cash, cash equivalents, and investments. The Company’s cash, cash equivalents, and investments are held by financial institutions that management believes are of high credit quality. The Company’s investment policy limits investments to fixed income securities denominated and payable in U.S. dollars such as U.S. government obligations, money market instruments and funds, corporate bonds, commercial paper, and asset-backed securities and places restrictions on maturities and concentrations by type and issuer. Such deposits may, at times, exceed federally insured limits. The Company has not experienced any losses on its deposits of cash and cash equivalents and its accounts are monitored by management to mitigate risk. The Company is exposed to credit risk in the event of default by the financial institutions holding its cash and cash equivalents, corporate issuers, and other financial instruments, to the extent recorded in the Consolidated Balance Sheets.

The Company is exposed to credit losses primarily through receivables from customers and collaborators and through its available-for-sale debt securities. For trade receivables and other instruments, the Company uses a forward-looking expected loss model that generally results in the earlier recognition of allowances for losses. For available-for-sale debt securities with unrealized losses, the losses are recognized as allowances rather than as reductions in the amortized cost of the securities.

The Company’s expected loss allowance methodology for the receivables is developed using historical collection experience, current and future economic market conditions, a review of the current aging status and financial condition of the entities. Specific allowance amounts are established to record the appropriate allowance for customers that have a higher probability of default. Balances are written off when determined to be uncollectible. The Company’s expected loss allowance methodology for the debt securities is developed by reviewing the extent of the unrealized loss, the size, term, geographical location, and industry of the issuer, the issuers’ credit ratings and any changes in those ratings, as well as reviewing current and future economic market conditions and the issuers’ current status and financial condition. There was no allowance for losses on available-for-sale debt securities which were attributable to credit risk for the years ended December 31, 2023 and 2022.

The Company is dependent on third-party manufacturers to supply products for research and development activities in its programs. In particular, the Company relies and expects to continue to rely on a small number of manufacturers to supply it with its requirements for the active pharmaceutical ingredients and formulated drugs related to these programs. These programs could be adversely affected by a significant interruption in the supply of active pharmaceutical ingredients and formulated drugs.

Inventory

The Company values inventory at the lower of cost and net realizable value and determines the cost of inventory using the average-cost method. The Company expenses costs associated with the manufacture of product candidates prior to regulatory approval. Inventories consist of currently approved products. The Company periodically reviews its inventories for excess amounts or obsolescence and writes down obsolete or otherwise unmarketable inventory to its estimated net realizable value. Management determines excess inventory based on expected future demand. Estimates related to future demand are sensitive to significant inputs and assumptions such as acceptance by patients and physicians and the availability of formulary coverage and adequate reimbursement from private third-party payers for the product.

Property, Plant, and Equipment

Property, plant, and equipment are stated at cost, less accumulated depreciation and amortization. Depreciation and amortization is computed using the straight-line method over the estimated useful lives of the respective assets. Depreciation and amortization begins when the asset is placed in service. Interest costs incurred during the construction of major capital projects are capitalized until the underlying asset is ready to be placed in service. Maintenance and repairs are charged to operations as incurred. Upon sale or retirement of assets, the cost and related accumulated depreciation or amortization are removed from the balance sheet and the resulting gain or loss, if any, is reflected in operations. See “Note 4. Balance Sheet Components” for further disclosure on the useful lives of property, plant, and equipment.

Intangible Assets

Finite-lived intangibles consist of contractual payments made for certain milestones achieved with collaboration partners. The contractual payments are recorded as intangible assets and are amortized over their estimated useful lives. The Company reviews its definite-lived intangible assets when events or circumstances may indicate that the carrying value of these assets is not recoverable and exceeds their fair value. The Company measures fair value based on the estimated future undiscounted cash flows associated with these assets in addition to other assumptions and projections that the Company deems to be reasonable and supportable.

Indefinite-lived intangibles consist of acquired in-process research and development, or IPR&D. IPR&D assets represent capitalized incomplete research projects that the Company acquired through business combinations. Such assets are initially measured at their acquisition date fair values and are tested for impairment annually and whenever events or changes in circumstances indicate that the carrying amount may not be recoverable. When development of the project is complete, which generally occurs when regulatory approval to market a product is obtained, the associated assets will be deemed finite-lived and will be amortized over a period that best reflects the economic benefits provided by these assets.

If it is determined that an intangible asset becomes impaired, the carrying value is written down to its fair value with the related impairment charge recognized in Consolidated Statements of Operations in the period in which the impairment occurs. The Company has not recorded any impairments of intangible assets to date.

Goodwill

Goodwill represents the excess of purchase price over fair value of net assets acquired in a business combination and is not amortized. Goodwill is subject to impairment testing at least annually during the fourth quarter or when a triggering event occurs that could indicate a potential impairment. If it is determined that the goodwill becomes impaired, the carrying value is written down to its fair value with the related impairment charge recognized in Consolidated Statements of Operations in the period in which the impairment occurs. The Company has not recorded any impairments of goodwill.

Impairment of Long-Lived Assets

The Company evaluates its long-lived assets, including property and equipment, for impairment whenever events or changes in circumstances indicate that the carrying value of these assets may not be recoverable. Recoverability of these assets is measured by comparison of the carrying amount of each asset to the future undiscounted cash flows expected to result from the use of the asset and its eventual disposition. If the asset is considered to be impaired, the amount of any impairment is measured as the difference between the carrying value and the fair value of the impaired asset. The Company has not recorded material impairment of any long-lived assets.

Accruals of Research and Development Costs

The Company records accruals for estimated costs of research, preclinical and clinical studies and manufacturing development. These costs are a significant component of the Company’s research and development expenses. A substantial portion of the Company’s ongoing research and development activities are conducted by third-party service providers, including contract research organizations. The Company accrues the costs incurred under its agreements with these third parties based on actual work completed in accordance with agreements established with these third parties. The Company determines the actual costs through obtaining information from external service providers as to the progress or stage of completion of the services and the agreed-upon fee to be paid for such services.

Revenue Recognition

Product Sales

The Company sells its approved products through a limited number of distributors. Under ASC 606, revenue from product sales is recognized at the point in time when control is transferred to these distributors. The Company also recognizes revenue from sales of certain products on a “named patient” basis, which are allowed in certain countries prior to the commercial approval of the product. Prior to recognizing revenue, the Company makes estimates of the transaction price, including any variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Product sales are recorded net of estimated government-mandated rebates and chargebacks, estimated product returns, and other deductions.

Provisions for returns and other adjustments are provided for in the period the related revenue is recorded, as estimated by management. These reserves are based on estimates of the amounts earned or to be claimed on the related sales and are reviewed periodically and adjusted as necessary. The Company’s estimates of government mandated rebates, chargebacks, estimated product returns, and other deductions depends on the identification of key customer contract terms and conditions, as well as estimates of sales volumes to different classes of payors. If actual results vary, the Company may need to adjust these estimates, which could have a material effect on earnings in the period of the adjustment.

Collaboration, License, and Royalty Revenue

The Company has certain license and collaboration agreements that are within the scope of Accounting Standards Codification, or ASC, 808, Collaborative Agreements, which provides guidance on the presentation and disclosure of collaborative arrangements. Generally, the classification of the transactions under the collaborative arrangements is determined based on the nature of contractual terms of the arrangement, along with the nature of the operations of the participants. The Company records its share of collaboration revenue, net of transfer pricing related to net sales in the period in which such sales occur, if the Company is considered as an agent in the arrangement. The Company is considered an agent when the collaboration partner controls the product before transfer to the customers and has the ability to direct the use of and obtain substantially all of the remaining benefits from the product. Funding received related to research and development services and commercialization costs is generally classified as a reduction of research and development expenses and selling, general and administrative expenses, respectively, in the Consolidated Statements of Operations, because the provision of such services for collaborative partners are not considered to be part of the Company’s ongoing major or central operations.

The Company utilizes certain information from its collaboration partners to record collaboration revenue, including revenue from the sale of the product, associated reserves on revenue, and costs incurred for development and sales activities. For the periods covered in the financial statements presented, there have been no material changes to prior period estimates of revenues and expenses. The Company also records royalty revenues under certain of the Company’s license or collaboration agreements in exchange for license of intellectual property.

The Company sold the right to receive certain royalty payments from net sales of Crysvita in certain territories to RPI Finance Trust, or RPI, an affiliate of Royalty Pharma, and to OCM LS23 Holdings LP, an investment vehicle for Ontario Municipal Employees Retirement System, or OMERS, as further described in “Note 10. Liabilities for Sales of Future Royalties.” The Company records the royalty revenue from the net sales of Crysvita in the applicable territories on a prospective basis as non-cash royalty revenue in the Consolidated Statements of Operations over the term of the applicable arrangement.

The terms of the Company’s collaboration and license agreements may contain multiple performance obligations, which may include licenses and research and development activities. The Company evaluates these agreements under ASC 606, Revenue from Contracts with Customers, or ASC 606, to determine the distinct performance obligations. The Company analogizes to ASC 606 for the accounting for distinct performance obligations for which there is a customer relationship. Prior to recognizing revenue, the Company makes estimates of the transaction price, including variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Total consideration may include nonrefundable upfront license fees, payments for research and development activities, reimbursement of certain third-party costs, payments based upon the achievement of specified milestones, and royalty payments based on product sales derived from the collaboration.

If there are multiple distinct performance obligations, the Company allocates the transaction price to each distinct performance obligation based on its relative standalone selling price. The standalone selling price is generally determined based on the prices charged to customers or using expected cost-plus margin. The Company estimates the efforts needed to complete the performance obligations and recognizes revenue by measuring the progress towards complete satisfaction of the performance obligations using input measures.

Deferred Compensation Plan

The Company maintains a nonqualified deferred compensation plan whereby certain employees and members of the board of directors are able to defer certain equity awards and other compensation. Amounts deferred are invested into shares of the Company's common stock, mutual funds, and other investment options. The plan complies with the provisions of Section 409A of the Internal Revenue Code. All of the various mutual funds held in the plan are classified as trading securities and recorded at fair value in other non-current assets in the Consolidated Balance Sheets with changes in fair value recognized as earnings in the period they occur. The short-term portion of the corresponding liability for the plan is included in accrued expenses. The long-term portion of the liability is included in other non-current liabilities in the Consolidated Balance Sheets. Certain equity awards deferred under the plan are required to be settled through the issuance of Company stock. These awards are recorded as treasury stock and deferred compensation obligation within stockholders’ equity.

Leases

Lease agreements are evaluated to determine whether an arrangement is or contains a lease in accordance with ASC 842, Leases. The Company determines if an arrangement includes a lease at inception. Right-of-use lease assets and lease liabilities are

recognized based on the present value of the future minimum lease payments over the lease term at the commencement date. The right-of-use lease asset includes any lease payments made and excludes lease incentives. Incremental borrowing rate is used in determining the present value of future payments. The Company applies a portfolio approach to the property leases to apply an incremental borrowing rate to leases with similar lease terms. The lease terms may include options to extend or terminate the lease. The Company recognizes the options to extend the lease as part of the right-of-use lease assets and lease liabilities only if it is reasonably certain that the option would be exercised. Lease expense for minimum lease payments is recognized on a straight-line basis over the non-cancelable lease term. The Company has elected to not separate lease and non-lease components. See “Note 9. Leases” for further disclosure.

Comprehensive Loss

Comprehensive loss is the change in stockholders’ equity from transactions and other events and circumstances other than those resulting from investments by stockholders and distributions to stockholders. The Company’s other comprehensive loss is comprised of unrealized gains and losses on investments in available-for-sale securities and foreign currency translation adjustments.

Research and Development

Research and development costs are expensed as incurred and consist of salaries and benefits, stock-based compensation expense, lab supplies and facility costs, as well as fees paid to other nonemployees and entities that conduct certain research and development activities on the Company’s behalf. Amounts incurred in connection with license agreements are also included in research and development expense. Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are deferred. The deferred amounts are expensed as the related goods are delivered or the services are performed.

Stock-Based Compensation

Stock-based awards issued to employees, including stock options, performance stock options, or PSOs, restricted stock units, or RSUs, and performance stock units, or PSUs are recorded at fair value as of the grant date and recognized as expense on a straight-line basis over the employee’s requisite service period (generally the vesting period). PSOs and PSUs vest only if certain specified criteria are achieved and the employees’ continued service requirements are met; therefore, the expense recognition occurs when the likelihood of the PSOs and PSUs being earned is deemed probable. Stock compensation expense on awards expected to vest is recognized net of estimated forfeitures.

Income Taxes

The Company uses the liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are determined based on the differences between the financial reporting and the tax bases of assets and liabilities and are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. The Company must then assess the likelihood that the resulting deferred tax assets will be realized. A valuation allowance is provided when it is more likely than not that some portion or all of a deferred tax asset will not be realized. Due to the Company’s lack of earnings history, the net deferred tax assets have been fully offset by a valuation allowance.

In conjunction with the acquisition of Dimension Therapeutics, Inc., or Dimension, a deferred tax liability was recorded reflecting the tax impact of the difference between the book basis and tax basis of acquired IPR&D. Such deferred income tax liability is not used to offset deferred tax assets when analyzing the Company’s valuation allowance as the acquired IPR&D is considered to have an indefinite life until the Company completes or abandons development of the acquired IPR&D.

The Company recognizes benefits of uncertain tax positions if it is more likely than not that such positions will be sustained upon examination based solely on their technical merits, as the largest amount of benefit that is more likely than not to be realized upon the ultimate settlement. The Company’s policy is to recognize interest and penalties related to the underpayment of income taxes as a component of income tax expense or benefit. To date, there have been no interest or penalties charged in relation to the unrecognized tax benefits.

Foreign Currency

Assets and liabilities of non-U.S. subsidiaries that operate in a local currency environment, where the local currency is the functional currency, are translated to U.S. dollars at exchange rates in effect at the balance sheet date, with the resulting translation adjustments directly recorded to a separate component of accumulated other comprehensive loss. Income and expense accounts are translated at average exchange rates for the period. Transactions which are not in the functional currency of the entity are remeasured into the functional currency and gains or losses resulting from the remeasurement recorded in other income (expense).

Net Loss per Share

Basic net loss per share is calculated by dividing the net loss by the weighted-average number of shares of common stock outstanding during the period, without consideration for common stock equivalents. Shares of common stock into which pre-funded warrants may be exercised are considered outstanding for the purposes of computing basic net loss per share because the shares may be issued for little or no consideration, are fully vested and are exercisable after the original issuance date. Diluted net loss per share is the same as basic net loss per share, since the effects of potentially dilutive securities are antidilutive. In periods when we have incurred a net loss, options and warrants to purchase common stock are considered common stock equivalents, but have been excluded from the calculation of diluted net loss per share, as their effect is antidilutive.

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Fair Value Measurements

12 Months Ended

Dec. 31, 2023

Fair Value Disclosures [Abstract]

Fair Value Measurements

3.Fair Value Measurements

Financial assets and liabilities are recorded at fair value. The carrying amount of certain financial instruments, including cash and cash equivalents, accounts receivable, accounts payable and accrued liabilities approximate fair value due to their relatively short maturities. Assets and liabilities recorded at fair value on a recurring basis in the balance sheets are categorized based upon the level of judgment associated with the inputs used to measure their fair values. Fair value is defined as the exchange price that would be received for an asset or an exit price that would be paid to transfer a liability in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants on the measurement date. The authoritative guidance on fair value measurements establishes a three-tier fair value hierarchy for disclosure of fair value measurements as follows:

Level 1—Inputs are unadjusted, quoted prices in active markets for identical assets or liabilities at the measurement date;

Level 2—Inputs are observable, unadjusted quoted prices in active markets for similar assets or liabilities, unadjusted quoted prices for identical or similar assets or liabilities in markets that are not active, or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the related assets or liabilities; and

Level 3—Unobservable inputs that are significant to the measurement of the fair value of the assets or liabilities that are supported by little or no market data.

The Company’s financial instruments consist of Level 1, Level 2, and Level 3 assets. Where quoted prices are available in an active market, securities are classified as Level 1. Money market funds and U.S. Government treasury bills are classified as Level 1. Level 2 assets consist primarily of corporate bonds, asset backed securities, commercial paper, U.S. Government Treasury and agency securities, and debt securities in government-sponsored entities based upon quoted market prices for similar movements in active markets, quoted prices for identical or similar instruments in markets that are not active and model-based valuation techniques for which all significant inputs are observable in the market or can be corroborated by observable market data for substantially the full term of the assets. Where applicable these models project future cash flows and discount the future amounts to a present value using market-based observable inputs obtained from various third-party data providers, including but not limited to, benchmark yields, interest rate curves, reported trades, broker/dealer quotes and reference data.

The Company determines the fair value of its equity investments in Solid Biosciences, Inc., or Solid, by using the quoted market prices, which are Level 1 fair value measurements.

The following tables set forth the fair value of the Company’s financial assets remeasured on a recurring basis based on the three-tier fair value hierarchy (in thousands):

	December 31, 2023
	Level 1		Level 2		Level 3		Total
Financial Assets:
Money market funds	$	162,289	$	—	$	—	$	162,289
Certificates of deposit and time deposits		—		17,986		—		17,986
Corporate bonds		—		215,166		—		215,166
Commercial paper		—		20,620		—		20,620
Asset-backed securities		—		2,712		—		2,712
U.S. Government Treasury and agency securities		57,437		259,605		—		317,042
Investment in Solid common stock		3,204		—		—		3,204
Deferred compensation assets		—		10,220		—		10,220
Total financial assets	$	222,930	$	526,309	$	—	$	749,239
Financial Liabilities:
Deferred compensation liabilities	$	—	$	10,365	$	—	$	10,365

	December 31, 2022
	Level 1		Level 2		Level 3		Total
Financial Assets:
Money market funds	$	102,847	$	—	$	—	$	102,847
Certificates of deposit and time deposits		—		25,972		—		25,972
Corporate bonds		—		427,598		—		427,598
Commercial paper		—		135,393		—		135,393
Asset-backed securities		—		11,980		—		11,980
U.S. Government Treasury and agency securities		27,645		129,345		—		156,990
Debt securities in government-sponsored entities		—		15,855		—		15,855
Investment in Solid common stock		2,807		—		—		2,807
Deferred compensation assets		—		4,575		—		4,575
Total financial assets	$	133,299	$	750,718	$	—	$	884,017
Financial Liabilities:
Deferred compensation liabilities	$	—	$	4,657	$	—	$	4,657

Deferred compensation assets are recorded at fair value in other non-current assets in the Consolidated Balance Sheets. There have been no significant gains or losses on deferred compensation assets for the periods presented.

Deferred compensation liabilities consist of short-term liabilities of $0.2 million and nil as of December 31, 2023 and 2022, respectively, included in accrued liabilities on the Consolidated Balance Sheets, and long-term liabilities of $10.1 million and $4.7 million as of December 31, 2023 and 2022, respectively, included in other non-current liabilities on the Consolidated Balance Sheets.

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Balance Sheet Components

12 Months Ended

Dec. 31, 2023

Investments, Debt and Equity Securities [Abstract]

Balance Sheet Components

4.Balance Sheet Components

Cash Equivalents and Marketable Debt Securities

The fair values of cash equivalents and marketable debt securities classified as available-for-sale securities consisted of the following (in thousands):

	December 31, 2023
			Gross Unrealized
	Amortized Cost		Gains		Losses			Estimated Fair Value
Money market funds	$	162,289	$	—	$	—		$	162,289
Certificates of deposit and time deposits		17,986		—		—			17,986
Corporate bonds		214,792		711		(337	)		215,166
Commercial paper		20,620		—		—			20,620
Asset-backed securities		2,715		—		(3	)		2,712
U.S. Government Treasury and agency securities		316,160		982		(100	)		317,042
Total	$	734,562	$	1,693	$	(440	)	$	735,815

	December 31, 2022
			Gross Unrealized
	Amortized Cost		Gains		Losses			Estimated Fair Value
Money market funds	$	102,847	$	—	$	—		$	102,847
Certificates of deposit and time deposits		25,972		—		—			25,972
Corporate bonds		432,211		87		(4,700	)		427,598
Commercial paper		135,393		—		—			135,393
Asset-backed securities		12,002		—		(22	)		11,980
U.S. Government Treasury and agency securities		157,933		320		(1,263	)		156,990
Debt securities in government-sponsored entities		16,005		—		(150	)		15,855
Total	$	882,363	$	407	$	(6,135	)	$	876,635

At December 31, 2023, the remaining contractual maturities of available-for-sale securities were less than three years. There have been no significant realized gains or losses on available-for-sale securities for the periods presented.

Inventory

Inventory consists of the following (in thousands):

	December 31,
	2023		2022
Work-in-process	$	18,859	$	17,486
Finished goods		15,110		9,280
Total inventory	$	33,969	$	26,766

Property, Plant, and Equipment, net

Property, plant, and equipment, net consists of the following (in thousands):

		December 31,
	Useful life (years)	2023			2022
Building	20-30	$	181,356		$	2,798
Leasehold improvements	Shorter of lease term or estimated useful life		58,683			43,941
Research and development equipment	5		56,347			50,291
Furniture and office equipment	5		6,419			5,540
Computer equipment and software	3-5		16,196			13,876
Manufacturing equipment	5-15		37,297			570
Land	Not applicable		16,619			16,619
Construction-in-progress	Not applicable		867			189,448
Other	Varies by asset		183			24
Property, plant, and equipment, gross			373,967			323,107
Less: accumulated depreciation			(83,401	)		(63,381	)
Property, plant, and equipment, net		$	290,566		$	259,726

Depreciation expense for the years ended December 31, 2023, 2022, and 2021 was $22.2 million, $15.0 million and $12.9 million, respectively. Amortization of leasehold improvements and software is included in depreciation expense.

Construction in progress reflects amounts incurred for construction or improvements of property or costs for equipment that has not been placed in service. The construction-in-progress balance as of December 31, 2022 is primarily the construction costs for the gene therapy manufacturing facility in Bedford, Massachusetts.

Accrued Liabilities

Accrued liabilities consists of the following (in thousands):

	December 31,
	2023		2022
Research, clinical study, and manufacturing expenses	$	65,326	$	73,558
Payroll and related expenses		82,936		78,938
Other		48,224		52,182
Total accrued liabilities	$	196,486	$	204,678

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Intangible Assets, Net

12 Months Ended

Dec. 31, 2023

Intangible Assets, Net (Excluding Goodwill) [Abstract]

Intangible Assets, Net

5.Intangible Assets, net

Indefinite-lived Intangibles

The Company has IPR&D assets of $129.0 million as of December 31, 2023 and 2022. IPR&D assets represent the fair value of acquired programs to develop an AAV gene therapy for OTC deficiency and to develop an AAV gene therapy for glycogen storage disease type Ia. The fair value of IPR&D assets acquired was determined based on the discounted present value of each research project’s projected cash flows using an income approach, including the application of probability factors related to the likelihood of success of the program reaching final development and commercialization. Additionally, the projections consider the relevant market sizes and growth factors, estimated future cash flows from product sales resulting from completed products and in-process projects and timing and costs to complete the in-process projects. The rates utilized to discount the net cash flows to their present value are commensurate with the stage of development of the projects and uncertainties in the economic estimates used in the projections. IPR&D assets are considered to be indefinite-life until the completion or abandonment of the associated research and development efforts.

Finite-lived Intangibles

Subsequent to the FDA approval of Dojolvi for the treatment of LC-FAOD in 2020, the Company recorded $4.8 million for the attainment of various development and commercial milestones as finite-lived intangible assets which are amortized over a weighted-average useful life of 5.7 years.

In January 2022, the Company announced a collaboration with Regeneron to commercialize Evkeeza for HoFH outside of the U.S. Upon closing of the transaction in January 2022, the Company paid Regeneron a $30.0 million upfront payment. During the year ended December 31, 2023, a $10.0 million regulatory milestone was achieved. As both the upfront payment and the regulatory milestone are related to the Company’s use of intellectual property for Evkeeza for HoFH, these amounts were recorded as intangible assets, which are amortized over a weighted-average useful life of ten years.

The Company's intangible assets were as follows:

	December 31, 2023
	Gross Carrying Amount		Weighted-Average Life (Years)		Accumulated Amortization			Net Carrying Amount
Indefinite-lived intangibles	$	129,000		—	$	—		$	129,000
Finite-lived intangibles		44,775		9.6		(7,504	)		37,271
Total intangible assets	$	173,775		—	$	(7,504	)	$	166,271

	December 31, 2022
	Gross Carrying Amount		Weighted-Average Life (Years)		Accumulated Amortization			Net Carrying Amount
Indefinite-lived intangibles	$	129,000		—	$	—		$	129,000
Finite-lived intangibles		34,775		9.9		(3,670	)		31,105
Total intangible assets	$	163,775		—	$	(3,670	)	$	160,105

The Company recorded costs of sales of $3.8 million, $3.2 million and $0.3 million for the years ended December 31, 2023, 2022, and 2021, respectively, related to the amortization of the intangible assets.

The expected amortization of the intangible assets, as of December 31, 2023, for each of the next five years and thereafter is as follows:

2024	$	4,903
2025		4,903
2026		4,903
2027		4,462
2028		4,022
Thereafter		14,078
Total	$	37,271

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Revenue

12 Months Ended

Dec. 31, 2023

Revenue from Contract with Customer [Abstract]

Revenue

6.Revenue

The following table disaggregates total revenues from external customers by product sales, royalty revenue, and collaboration and license revenue (in thousands):

	Year Ended December 31,
	2023		2022		2021
Product sales:
Crysvita	$	75,697	$	42,678	$	21,422
Mepsevii		30,441		20,637		16,035
Dojolvi		70,633		55,612		39,560
Evkeeza		3,642		—		—
Total product sales		180,413		118,927		77,017
Crysvita royalty revenue		182,652		21,692		17,951
Collaboration and license revenue:
Crysvita collaboration revenue in Profit-Share Territory		69,705		215,024		171,198
Crysvita royalty revenue in European Territory		—		—		244
Daiichi Sankyo		1,479		7,686		84,996
Total collaboration and license revenue		71,184		222,710		256,438
Total revenues	$	434,249	$	363,329	$	351,406

The following table disaggregates total revenues based on geographic location (in thousands):

	Year Ended December 31,
	2023		2022		2021
North America	$	307,149	$	281,088	$	301,110
Latin America		77,342		44,711		23,636
Europe		47,534		36,369		26,660
Japan		2,224		1,161		—
Total revenues	$	434,249	$	363,329	$	351,406

The following table presents the activity and ending balances for sales-related accruals and allowances (in thousands):

	Year Ended December 31,
	2023			2022			2021
Balance of product sales reserve at beginning of year	$	11,487		$	7,181		$	3,913
Provisions		18,761			13,525			9,586
Payments		(12,746	)		(9,613	)		(6,120	)
Adjustments		(473	)		394			(198	)
Balance of product sales reserve at end of year	$	17,029		$	11,487		$	7,181

The following table presents changes in the contract liabilities for the years ended December 31, 2023 and 2022 (in thousands):

	Year Ended December 31,
	2023			2022
Balance of contract liabilities at beginning of period	$	1,479		$	9,076
Additions		—			89
Deductions		(1,479	)		(7,686	)
Balance of contract liabilities at end of period, net	$	—		$	1,479

See Note 8 for additional details on contract liabilities activities.

The Company’s largest accounts receivable balance was from a collaboration partner and was 53% and 68% of the total accounts receivable balance as of December 31, 2023 and 2022, respectively.

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GeneTx Acquisition

12 Months Ended

Dec. 31, 2023

Business Combinations [Abstract]

Acquisition

7.GeneTx Acquisition

In August 2019, the Company entered into a Program Agreement and a Unitholder Option Agreement with GeneTx Biotherapeutics LLC, or GeneTx, to collaborate on the development of GeneTx’s GTX-102, an ASO for the treatment of Angelman syndrome. In July 2022, pursuant to the terms of the Unitholder Option Agreement, as amended, the Company exercised the option to acquire GeneTx and entered into a Unit Purchase Agreement, or the Purchase Agreement, pursuant to which the Company purchased all the outstanding units of GeneTx. In accordance with the terms of the Purchase Agreement, the Company paid the option exercise price of $75.0 million and an additional $15.6 million to acquire the outstanding cash of GeneTx, and adjustments for working capital and transaction expenses of $0.6 million, for a total purchase consideration of $91.2 million. The Company may be required to make payments of up to $190.0 million upon the achievement of certain milestones, including up to $30.0 million in milestone payments upon achievement of the earlier of initiation of a Phase 3 clinical study or product approvals in Canada and the U.K., up to $85.0 million in additional regulatory approval milestones for the achievement of U.S. and EU product approvals, and up to $75.0 million in commercial milestone payments based on annual worldwide net product sales. The Company will also pay tiered mid- to high single-digit percentage royalties based on licensed product annual net sales. If the Company receives and resells an FDA priority review voucher, or PRV, in connection with a new drug application approval, GeneTx is entitled to receive a portion of proceeds from the sale or a cash payment from the Company if the Company choses to retain the PRV. As part of the Company's acquisition of GeneTx, the Company assumed a License Agreement with Texas A&M University, or TAMU. Under this agreement, TAMU is eligible to receive from the Company up to $23.5 million upon the achievement of various future milestones, a nominal annual license fee that may increase up to a maximum of $2.0 million, as well as royalties in the mid-single-digits of net sales.

The transaction was accounted as an asset acquisition, as substantially all of the fair value of the gross assets acquired was concentrated in a single identifiable in-process research and development intangible asset. Prior to the achievement of certain development and regulatory milestones, the acquired in-process research and development intangible asset has not yet reached technological feasibility and has no alternative future use. Accordingly, the Company recorded the acquisition price of $75.0 million, net of cash and working capital acquired, as in-process research and development expense during the year ended December 31, 2022.

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License and Research Agreements

12 Months Ended

Dec. 31, 2023

Research Grant Agreement [Abstract]

License and Research Agreements

8.License and Research Agreements

Kyowa Kirin Co., Ltd.

In August 2013, the Company entered into a collaboration and license agreement with Kyowa Kirin Co., Ltd., or KKC. Under the terms of this collaboration and license agreement, as amended, the Company and KKC collaborate on the development and commercialization of Crysvita in the field of orphan diseases in the U.S. and Canada, or the Profit-Share Territory, and in the European Union, United Kingdom, and Switzerland, or the European Territory, and the Company has the right to develop and commercialize such products in the field of orphan diseases in Mexico and Central and South America, or Latin America.

Development Activities

In the field of orphan diseases, except for ongoing studies being conducted by KKC, the Company was the lead party for development activities in the Profit-Share Territory and in the European Territory until the applicable transition date. The Company shared the costs for development activities in the Profit-Share Territory and the European Territory conducted pursuant to the development plan before the applicable transition date equally with KKC. In April 2023, which was the transition date for the Profit-Share Territory, KKC became the lead party and became responsible for the costs of the subsequent development activities. However, the Company will continue to equally share in the costs of the studies with KKC that commenced prior to the applicable transition date.

The collaboration and license agreements are within the scope of ASC 808, which provides guidance on the presentation and disclosure of collaborative arrangements.

Collaboration and Royalty Revenue for Sales in the Profit-Share Territory

The Company and KKC shared commercial responsibilities and profits in the Profit-Share Territory until April 2023. Under the collaboration agreement, KKC manufactured and supplied Crysvita for commercial use in the Profit-Share Territory and charged the Company a transfer price of 30% of net sales in 2023, and 35% prior to December 31, 2022. The remaining profit or loss after supply

costs from commercializing products in the Profit-Share Territory was shared between the Company and KKC on a 50/50 basis until April 2023. In April 2023, commercialization responsibilities for Crysvita in the Profit-Share Territory transitioned to KKC. Thereafter, the Company is entitled to receive a tiered double-digit revenue share from the mid-20% range up to a maximum rate of 30%.

In 2022, the Company entered into an amendment to the collaboration agreement which granted the Company the right to continue to support KKC in commercial field activities in the U.S. through April 2024, subject to the limitations and conditions set forth in the amendment. The parties subsequently mutually agreed to extend the Company's right to continue to support KKC in commercial field activities in the U.S. through December 31, 2024, and as a result, the Company will continue to support commercial field efforts in the U.S. through a cost share arrangement through December 2024. After December 31, 2024, the Company’s rights to promote Crysvita in the U.S. will be limited to medical geneticists and the Company will solely bear its expenses for the promotion of Crysvita in the Profit-Share Territory.

As KKC was the principal in the sale transaction with the customer during the profit-share period, the Company recognized a pro-rata share of collaboration revenue, net of transfer pricing, in the period the sale occurs. The Company concluded that its portion of KKC’s sales in the Profit-Share Territory prior to April 2023 was analogous to a royalty and therefore recorded its share as collaboration revenue, similar to a royalty. Starting in April 2023, the Company began to record the royalty revenue as the underlying sales occur.

In July 2022, the Company sold to OMERS its right to receive 30% of the future royalty payments due to the Company based on net sales of Crysvita in the U.S. and Canada, subject to a cap, beginning in April 2023, as further described in Note 10. The Company records this revenue as royalty revenue.

Product Sales Revenue for Other Territories

The Company is responsible for commercializing Crysvita in Latin America and Turkey. The Company is considered the principal in these territories as the Company controls the product before it is transferred to the customer. Accordingly, the Company records revenue on a gross basis for the sale of Crysvita once the product is delivered and the risk and title of the product is transferred to the distributor. KKC has the option to assume responsibility for commercialization efforts in Turkey from the Company, after a certain minimum period.

Under the collaboration agreement, KKC manufactures and supplies Crysvita, which is purchased by the Company for sales in Latin American territories and charges the Company a transfer price of 30% of net sales. The transfer price on these sales was 35% prior to December 31, 2022. The Company also pays to KKC a low single-digit royalty on net sales in Latin America.

Total Crysvita revenue was as follows (in thousands):

	Year Ended December 31,
	2023		2022		2021
Revenue in profit-share territory:
Collaboration revenue	$	69,705	$	215,024	$	171,198
Royalty revenue		113,288		—		—
Non-cash royalty revenue		48,581		—		—
Total revenue in Profit-Share Territory		231,574		215,024		171,198
Product sales		75,697		42,678		21,422
Royalty revenue in European Territory		—		—		244
Non-cash royalty revenue in European Territories		20,783		21,692		17,951
Total Crysvita revenue	$	328,054	$	279,394	$	210,815

Royalty Revenue for Sales in the European Territory

KKC has the commercial responsibility for Crysvita in the European Territory. In December 2019, the Company sold its right to receive royalty payments based on sales in the European Territory to Royalty Pharma, effective January 1, 2020, as further described in Note 10. Prior to the Company’s sale of the royalty, the Company received a royalty of up to 10% on net sales in the European Territory, which was recognized as the underlying sales occur. Beginning in 2020, the Company records the royalty revenue as non-cash royalty revenues. The Company records this revenue as royalty revenue.

Collaboration Cost Sharing and Payments

Under the collaboration agreement, KKC and the Company share certain development and commercialization costs and as a result, the Company was reimbursed for these costs and operating expenses were reduced. Additionally, KKC is owed a transfer price fee and royalties on certain revenues and the Company recorded amounts owed to KKC in cost of sales. These amounts were recognized in the Company’s Statements of Operations in connection with the collaboration agreement with KKC as follows (in thousands):

	Year Ended December 31,
	2023			2022			2021
Research and development	$	(6,510	)	$	(15,974	)	$	(21,657	)
Selling, general and administrative	$	(17,199	)	$	(37,217	)	$	(32,629	)
Cost of sales	$	18,476		$	13,250		$	6,701

Collaboration Receivable and Payable

The Company had accounts receivable from KKC in the amount of $39.2 million and $27.5 million from profit-share revenue and royalties and other receivables recorded in other current assets of $1.1 million and $6.4 million and accrued liabilities of $5.3 million and $3.1 million from commercial and development activity reimbursements, as of December 31, 2023 and 2022, respectively.

Saint Louis University

In November 2010, the Company entered into a license agreement with Saint Louis University, or SLU. Under the terms of this license agreement, SLU granted the Company an exclusive worldwide license to make, have made, use, import, offer for sale, and sell therapeutics related to SLU’s beta-glucuronidase product for use in the treatment of human diseases.

The Company made a milestone payment of $0.1 million upon approval of Mepsevii for treatment of MPS 7. The Company is required to pay to SLU a low single-digit royalty on net sales of the licensed products in any country or region, upon reaching a certain level of cumulative worldwide sales of the product.

Baylor Research Institute

In September 2012, the Company entered into a license agreement with Baylor Research Institute, or BRI. Under the terms of this license agreement, as amended, BRI exclusively licensed to the Company its territories for certain intellectual property related to Dojolvi (triheptanoin) for the treatment of LC-FAOD.

For the years ended December 31, 2023 and 2022, the Company recorded nil and $2.5 million, respectively, for the attainment of various development and commercial milestones as finite-lived intangible assets. The Company is obligated to make additional future payments of up to $7.5 million contingent upon attainment of various development and commercial milestones. Additionally, the Company is paying BRI a mid- single-digit royalty on net sales of the licensed product in the licensed territories.

REGENXBIO, Inc.

The Company has a license agreement with REGENXBIO, Inc., or REGENX, for an exclusive, sublicensable, worldwide commercial license under certain intellectual property for preclinical and clinical research and development, and commercialization of drug therapies using REGENX's licensed patents for the treatment of hemophilia A, OTC deficiency, and GSD1a. The Company will pay an annual fee and certain milestone fees per disease indication, low to mid- single-digit royalty percentages on net sales of licensed products, and milestone and sublicense fees owed by REGENX to its licensors, contingent upon the attainment of certain development activities as outlined in the agreement.

The Company also has an option and license agreement with REGENX under which the Company has an exclusive, sublicensable, worldwide license to make, have made, use, import, sell, and offer for sale licensed products to treat Wilson disease and CDKL5 deficiency. For each disease indication, the Company is obligated to pay an annual maintenance fee of $0.1 million and up to $9.0 million upon achievement of various milestones, as well as mid- to high single-digit royalties on net sales of licensed products and mid- single-digit to low double-digit percentage sublicenses fees, if any.

In March 2020, the Company entered into a license agreement with REGENX, for an exclusive, sublicensable, worldwide license to REGENX’s NAV AAV8 and AAV9 vectors for the development and commercialization of gene therapy treatments for a rare metabolic disorder. In return for these rights, the Company made an upfront payment of $7.0 million. The Company will pay certain

annual fees of $0.1 million, milestone payments of up to $14.0 million, and royalties on any net sales of products incorporating the licensed intellectual property that range from a high single-digit to low double-digit royalty.

Bayer HealthCare LLC

The Company previously had a collaboration and license agreement with Bayer Healthcare LLC, or Bayer, to research, develop and commercialize AAV gene therapy products for the treatment of hemophilia A, or DTX 201. Under this agreement, Bayer had been granted an exclusive license to develop and commercialize one or more novel gene therapies for hemophilia A.

In October 2022, the Collaboration and License Agreement for DTX201 with Bayer was terminated and all licensed rights to DTX201 have reverted back to the Company. The Company also obtained rights to all necessary data and information to further develop DTX201 or another hemophilia A program through a royalty-free, worldwide, sublicensable, perpetual license.

University of Pennsylvania

The Company has a research, collaboration, and license agreement with University of Pennsylvania School of Medicine, or Penn, which provides the terms for the Company and Penn to collaborate with respect to the pre-clinical development of gene therapy products for the treatment of certain indications. Under the agreement, Penn granted the Company an exclusive, worldwide license to certain patent rights arising out of the research program, subject to certain retained rights, and a non-exclusive, worldwide license to certain Penn intellectual property, in each case to research, develop, make, have made, use, sell, offer for sale, commercialize and import licensed products in each indication for the term of the agreement. The Company will fund the cost of the research program in accordance with a mutually agreed-upon research budget and will be responsible for clinical development, manufacturing and commercialization of each indication. The Company may be obligated to make milestone payments of up to $5.0 million for each indication, if certain development milestones are achieved over time. The Company is also obligated to make milestone payments of up to $25.0 million per approved product if certain commercial milestones are achieved, as well as low to mid- single-digit royalties on net sales of each licensed product.

Arcturus Therapeutics Holdings Inc.

In October 2015, the Company entered into a Research Collaboration and License Agreement with Arcturus Therapeutics Holdings Inc., or Arcturus, to collaborate on the research and development of therapies for select rare diseases. Arcturus was responsible for conducting certain research services, funded by the Company, and the Company was responsible for development and commercialization costs.

On a product-by-product basis, the Company is obligated to make development and regulatory milestone payments of up to $24.5 million, and commercial milestone payments of up to $45.0 million if certain milestones are achieved. For the year ended December 31, 2021, the Company achieved a $1.0 million development milestone, which was paid with a corresponding credit received from Arcturus for prior research and collaboration activities. The Company is also obligated to pay Arcturus royalties on any net sales of products incorporating the licensed intellectual property that may range from a mid- single-digit to low double-digit percentage. There were no material expenses for this arrangement during the years ended December 31, 2023, 2022, and 2021.

In June 2019, the Company entered into an Equity Purchase Agreement and an amendment to the Research Collaboration and License Agreement, or License Agreement, to expand the field of use and increase the number of disease targets to include mRNA, DNA and siRNA therapeutics for up to 12 rare diseases. Pursuant to the agreements, the Company paid $6.0 million in cash upfront to Arcturus and purchased 2,400,000 shares of Arcturus’ common stock at a stated value of $10.00 per share, resulting in a total of $30.0 million of consideration paid at the close of the transaction. As a result, the Company received expanded license rights under the License Agreement, Arcturus common stock, and an option to purchase an additional 600,000 shares of Arcturus’ common stock at $16.00 per share. In May 2020, the Company exercised its option to purchase 600,000 shares of Arcturus common stock for a total purchase price of $9.6 million.

The Company’s investment in Arcturus was accounted at fair value, as the fair value was readily determinable. During the year ended December 31, 2022, the Company sold 500,000 shares of Arcturus common stock, at a weighted-average price of $20.39 per share. As of December 31, 2022, the Company held no shares of Arcturus common stock.

The changes in the fair value of the Company’s equity investment in Arcturus were as follows (in thousands):

	Arcturus Common Stock
December 31, 2021	$	18,505
Change in fair value		(8,411	)
Sale of shares		(10,094	)
December 31, 2022	$	—

Daiichi Sankyo

In March 2020, the Company executed a License and Technology Access Agreement, or the License Agreement, with Daiichi Sankyo Co., Ltd., or Daiichi Sankyo. Pursuant to the License Agreement, the Company granted Daiichi Sankyo a non-exclusive license to intellectual property, including know-how and patent applications, with respect to its Pinnacle PCLTM producer cell line platform, or Pinnacle PCL Platform, and HEK293 transient transfection manufacturing technology platforms for AAV-based gene therapy products.

Under the terms of the License Agreement, Daiichi Sankyo made an upfront payment of $125.0 million and an additional $25.0 million upon completion of the technology transfer of the Pinnacle PCL Platform and HEK293 platform. Daiichi Sankyo reimbursed the Company for all costs associated with the transfer of the manufacturing technology.

The Company also entered into a Stock Purchase Agreement, or SPA, with Daiichi Sankyo, pursuant to which Daiichi Sankyo purchased 1,243,913 shares of the Company’s common stock in exchange for $75.0 million in cash during the first quarter of 2020. The fair market value of the common stock issued to Daiichi Sankyo was $55.3 million based on the stock price of $44.43 per share on the date of issuance, resulting in a $19.7 million premium on the SPA.

In June 2020, the Company executed a subsequent license agreement, or the Sublicense Agreement, with Daiichi Sankyo for transfer of certain technology in consideration for an upfront payment of $8.0 million and annual maintenance fees, milestone payments, and royalties on any net sales of products incorporating the licensed intellectual property.

The Company evaluated the License Agreement and the Sublicense Agreement under ASC 606 and determined that the performance obligations under the agreements are (i) intellectual property with respect to its Pinnacle PCL Platform and HEK293 transient transfection manufacturing technology platform together with the initial technical assistance and technology transfer services, and (ii) the transfer of any know-how and improvements after the completion of the initial technology transfer through the end of the three year technology transfer period.

The Company allocated the total transaction price to the two performance obligations on a relative stand-alone selling price basis. Revenue allocated to the intellectual property and the technology transfer services was recognized over an initial period which was completed during the first quarter of 2022, measuring the progress toward complete satisfaction of the individual performance obligation using an input measure. Revenue for know-how and improvements after the completion of technology transfer was recognized on a straight-line basis over the remaining technology transfer period, which ended in March 2023, as it was expected that Daiichi Sankyo would receive and consume the benefits consistently throughout the period. The Company’s current obligations under the License Agreement and the Sublicense Agreement were completed following the conclusion of the technology transfer period. Total revenue recognized under the arrangement through December 31, 2023 was $183.3 million.

The Company recognized $1.5 million, $7.7 million, and $85.0 million for the years ended December 31, 2023, 2022, and 2021, respectively, in revenue related to this arrangement. Accordingly, the Company recorded contract liabilities of nil and $1.5 million, net, for this arrangement as of December 31, 2023 and 2022, respectively.

Mereo

In December 2020, the Company entered into a License and Collaboration Agreement with Mereo to collaborate on the development of setrusumab. Under the terms of the agreement, the Company will lead future global development of setrusumab in both pediatric and adult patients with OI. The Company was granted an exclusive license to develop and commercialize setrusumab in the U.S., Turkey, and the rest of the world, excluding the European Economic Area, United Kingdom, and Switzerland, or the

Mereo Territory, where Mereo retains commercial rights. Each party will be responsible for post-marketing commitments and commercial supply in their respective territories.

Upon the closing of the transaction in January 2021, the Company made a payment of $50.0 million to Mereo and will be required to make payments of up to $254.0 million upon the achievement of certain clinical, regulatory, and commercial milestones. The Company will pay for all global development costs as well as tiered double-digit percentage royalties to Mereo on net sales in the U.S., Turkey, and the rest of the world (excluding the Mereo Territory), and Mereo will pay the Company a fixed double-digit percentage royalty on net sales in the Mereo Territory.

Although Mereo is a variable interest entity, the Company is not the primary beneficiary as it does not have the power to direct the activities that would most significantly impact the economic performance of Mereo. Prior to the achievement of certain development milestones, all consideration paid to Mereo represents rights to potential future benefits associated with Mereo’s in-process research and development activities, which have not reached technological feasibility and have no alternative future use.

For the years ended December 31, 2023, 2022, and 2021, the Company recorded research and development expense of $9.0 million for the achievement of a clinical milestone, nil, and $50.0 million for the upfront payment, respectively.

Regeneron

In January 2022, the Company announced a collaboration with Regeneron Pharmaceuticals, or Regeneron, to commercialize Evkeeza for HoFH outside of the U.S. Evkeeza is approved in the U.S., where it is marketed by Regeneron, and in the EU and U.K. as a first-in-class therapy for use together with diet and other low-density lipoprotein-cholesterol-lowering therapies to treat adults and adolescents aged 12 years and older with HoFH. Pursuant to the terms of the agreement, the Company received the rights to develop, commercialize and distribute the product for HoFH in countries outside of the U.S. The Company is obligated to pay up to $63.0 million in future milestone payments, contingent upon the achievement of certain regulatory and sales milestones. The Company may share in certain costs for global trials led by Regeneron and also received the right to opt into other potential indications.

The collaboration agreement is within the scope of ASC 808 which provides guidance on the presentation and disclosure of collaborative arrangements. As the Company would be the principal in future sale transactions with the customer, the Company will recognize product sales and cost of sales in the period the related sales occur and the related revenue recognition criteria are met. Under the collaboration agreement, Regeneron supplies the product and charges the Company a transfer price from the low 20% range up to 40% on net sales, which is recognized as cost of sales in the Company’s Statement of Operations.

The Company paid Regeneron a $30.0 million upfront payment upon the closing of the transaction in January 2022, and during the year ended December 31, 2023, a $10.0 million regulatory milestone was achieved. As these payments are for the Company’s use of intellectual property for Evkeeza for HoFH, they were recorded as intangible assets. See Note 5 for additional details.

Under the collaboration agreement, the Company reimbursed Regeneron for development costs of $7.6 million, $7.3 million, and nil for the years ended December 31, 2023, 2022, and 2021, respectively, which were recorded as research and development expense on the Consolidated Statements of Operations. The Company had collaboration payables for this arrangement included in accrued liabilities on the Consolidated Balance Sheets of $10.6 million and $6.8 million as of December 31, 2023 and December 31, 2022, respectively. Additionally, Regeneron is owed a transfer price fee and royalties on certain revenues and the Company recorded amounts owed to Regeneron of $0.7 million in cost of sales on the Consolidated Statements of Operations for the year ended December 31, 2023.

Abeona

In May 2022, the Company announced an exclusive License Agreement for the AAV gene therapy for UX111 with Abeona for the treatment of MPS IIIA. Under the terms of the agreement, the Company assumed responsibility for the UX111 program and in return, Abeona is eligible to receive tiered royalties of up to 10% on net sales and commercial milestone payments of up to $30.0 million following regulatory approval of the product. Additionally, the Company entered into an Assignment and Assumption Agreement with Abeona to transfer and assign to the Company the exclusive license agreement between Nationwide Children’s Hospital, or NCH, and Abeona for certain rights related to UX111. Under this agreement, NCH is eligible to receive from the Company up to $1.0 million in development and regulatory milestones as well as royalties in the low single-digits of net sales.

The Company is obligated to pay Abeona certain prior development costs and other transition costs related to UX111. Prior to product regulatory approval, all consideration paid to Abeona represents rights to potential future benefits associated with Abeona’s in-process research and development activities, which have not reached technological feasibility and have no alternative future use. Accordingly, the value of the acquired intellectual property rights and clinical inventory as well as prior development costs and transition costs of $3.1 million, were recorded as research and development expense for the year ended December 31, 2022. The Company did not incur any other material costs related to this agreement in the years presented.

Solid Biosciences, Inc.

In October 2020, the Company entered into a strategic Collaboration and License Agreement with Solid Biosciences Inc., or Solid, and received an exclusive license for any pharmaceutical product that expresses Solid’s proprietary microdystrophin construct from AAV8 and variants thereof in clade E for use in the treatment of Duchenne muscular dystrophy and other diseases resulting from lack of functional dystrophin, including Becker muscular dystrophy. The Company is collaborating to develop products that combine Solid’s differentiated microdystrophin construct, the Company’s Pinnacle PCL Platform, and the Company’s AAV8 variants. Solid is providing development support and was granted an exclusive option to co-invest in products the Company develops for profit-share participation in certain territories. On a product-by-product basis, the Company is obligated to make development milestone payments of up to $25.0 million, regulatory milestone payments of up to $65.0 million, and commercial milestone payments of up to $165.0 million, if such milestones are achieved, as well as royalties on any net sales of products incorporating the licensed intellectual property that range from a low to mid-double-digit percentage. The royalty rate changes to mid- to high double-digit percentage if Solid decides to co-invest in the product.

The Company also entered into a Stock Purchase Agreement and the Investor Agreement with Solid, pursuant to which, the Company purchased 7,825,797 shares of Solid’s common stock for an aggregate purchase price of $40.0 million. In October 2022, Solid announced a 1 for 15 reverse stock split. After the split, the Company held 521,719 shares of Solid's common stock. The Company’s investment in Solid is being accounted at fair value, as the fair value is readily determinable. The Company recorded the common stock investment at $26.8 million on the transaction date, which was based on the quoted market price on the closing date.

Although Solid is a variable interest entity, the Company is not the primary beneficiary as it does not have the power to direct the activities that would most significantly impact the economic performance of Solid. Prior to the achievement of certain development milestones, all consideration paid to Solid represents rights to potential future benefits associated with Solid’s in-process research and development activities, which have not reached technological feasibility and have no alternative future use. Accordingly, the remaining $13.2 million of the total $40.0 million paid as consideration was attributed to the license rights obtained and was recorded as in-process research and development expense during the year ended December 31, 2020.

The changes in the fair value of the Company’s investment in Solid’s common stock were as follows (in thousands):

	Solid Common Stock
December 31, 2021	$	13,695
Change in fair value		(10,888	)
December 31, 2022		2,807
Change in fair value		397
December 31, 2023	$	3,204

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Leases

12 Months Ended

Dec. 31, 2023

Lessee Disclosure [Abstract]

Leases

9.Leases

The Company leases office space and research, testing and manufacturing laboratory space in various facilities in Novato and Brisbane, California, in Somerville, and Woburn, Massachusetts, and in certain foreign countries, under operating agreements expiring at various dates through 2029. Certain lease agreements include options for the Company to extend the lease for multiple renewal periods and provide for annual minimum increases in rent, usually based on a consumer price index or annual minimum increases. None of these optional periods have been considered in the determination of the right-of-use lease asset or the lease liability for the leases as the Company did not consider it reasonably certain that it would exercise any such options. The Company recognizes lease expense on a straight-line basis over the non-cancelable term of its operating leases. The variable lease expense primarily consists of common area maintenance and other operating costs.

The components of lease expense were as follows (in thousands):

	Year Ended December 31,
	2023		2022		2021
Operating lease expense	$	12,883	$	11,775	$	11,209
Variable lease expense		5,272		4,785		4,142
Financing:
Amortization		203		343		310
Interest expense		—		37		58
Total	$	18,358	$	16,940	$	15,719

Cash paid for amounts included in the measurement of operating lease liabilities for the years ended December 31, 2023, 2022, and 2021 was $13.4 million, $13.1 million, and $11.8 million, respectively, and was included in net cash used in operating activities in the Consolidated Statements of Cash Flows.

Right-of-use lease assets were $23.9 million and $26.0 million as of December 31, 2023 and 2022, respectively, and were included in other non-current assets on the Consolidated Balance Sheets.

The following table summarizes maturities of lease liabilities and the reconciliation of lease liabilities as of December 31, 2023:

Year Ending December 31,	Operating
2024	$	16,234
2025		11,932
2026		8,430
2027		5,867
2028		5,887
Thereafter		6,009
Total future lease payments		54,359
Less: Amount representing interest		(11,190	)
Present value of future lease payments		43,169
Less: Lease liabilities, current		(12,595	)
Lease liabilities, non-current	$	30,574

Lease liabilities are based on the net present value of the remaining lease payments over the remaining lease term. For the years ended December 31, 2023 and 2022, the weighted-average remaining operating lease terms were 4.5 years and 3.0 years, the weighted-average remaining financing lease terms were nil and 2.8 years, the weighted-average discount rates used to determine the lease liability for operating leases were 9.6% and 6.7%, and the weighted-average discount rates used to determine the lease liability for finance leases were nil and 5.1% respectively.

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Liabilities for Sales of Future Royalties

12 Months Ended

Dec. 31, 2023

Deferred Revenue Disclosure [Abstract]

Liabilities for Sales of Future Royalties

10.Liabilities for Sales of Future Royalties

In December 2019, the Company entered into a Royalty Purchase Agreement with RPI. Pursuant to the agreement, RPI paid $320.0 million to the Company in consideration for the right to receive royalty payments effective January 1, 2020, arising from the net sales of Crysvita in the EU, the U.K., and Switzerland under the terms of the Company’s Collaboration and License Agreement with KKC dated August 29, 2013, as amended, or the KKC Collaboration Agreement. The agreement with RPI will automatically terminate, and the payment of royalties to RPI will cease, in the event aggregate royalty payments received by RPI are equal to or greater than $608.0 million prior to December 31, 2030, or in the event aggregate royalty payments received by RPI are less than $608.0 million prior to December 31, 2030, or when aggregate royalty payments received by RPI are equal to $800.0 million.

In July 2022, the Company entered into a Royalty Purchase Agreement with OMERS. Pursuant to the agreement, OMERS paid $500.0 million to the Company in consideration for the right to receive 30% of the future royalty payments due to the Company from KKC based on net sales of Crysvita in the U.S. and Canada under the terms of the KKC Collaboration Agreement. The calculation of royalty payments to OMERS is based on net sales of Crysvita beginning in April 2023 and will expire upon the earlier of the date on which aggregate payments received by OMERS equals $725.0 million or the date the final royalty payment is made to the Company under the KKC Collaboration Agreement.

Proceeds from these transactions were recorded as liabilities for sales of future royalties on the Consolidated Balance Sheets. Upon inception of the respective arrangements, the Company recorded $320.0 million and $500.0 million, net of transaction costs of $5.8 million and $9.1 million for RPI and OMERS, respectively, using the effective interest method over the estimated life of the applicable arrangement. In order to determine the amortization of the liabilities, the Company is required to estimate the total

amount of future royalty payments to be received by the Company and paid to RPI and OMERS, subject to the capped amount, over the life of the arrangements. The excess of future estimated royalty payments (subject to the capped amount) to RPI and OMERS, over the $314.2 million and $491.0 million, respectively, of net proceeds, is recorded as non-cash interest expense over the life of the arrangements. Consequently, the Company estimates an imputed interest on the unamortized portion of the liabilities and records interest expense relating to the transactions. The Company records the royalty revenue arising from the net sales of Crysvita in the applicable territories as royalty revenue in the Consolidated Statements of Operations over the term of the arrangements. Royalties earned under the RPI and OMERS arrangements from inception to December 31, 2023 have been $73.4 million and $48.6 million, respectively.

The Company periodically assesses the expected royalty payments using a combination of historical results, internal projections and forecasts from external sources. To the extent such payments are greater or less than the Company’s initial estimates or the timing of such payments is materially different than its original estimates, the Company will prospectively adjust the amortization of the liabilities and the effective interest rate. The Company’s effective annual interest rates were 6.2% and 7.8%, for RPI and OMERS, respectively, as of December 31, 2023.

There are a number of factors that could materially affect the amount and timing of royalty payments from KKC in the applicable territories, most of which are not within the Company’s control. Such factors include, but are not limited to, the success of KKC’s sales and promotion of Crysvita, changing standards of care, macroeconomic and inflationary pressures, the introduction of competing products, pricing for reimbursement in various territories, manufacturing or other delays, intellectual property matters, adverse events that result in governmental health authority imposed restrictions on the use of Crysvita, significant changes in foreign exchange rates as the royalty payments are made in U.S. dollars, or USD, while significant portions of the underlying sales of Crysvita are made in currencies other than USD, and other events or circumstances that could result in reduced royalty payments from sales of Crysvita, all of which would result in a reduction of royalty revenue and the non-cash interest expense over the life of the arrangement. Conversely, if sales of Crysvita in the relevant territories are more than expected, the royalty revenue and the non-cash interest expense recorded by the Company would be greater over the term of the arrangements.

The following table shows the activity within the liability account (in thousands):

	Liabilities for Sales of Future Royalties
	RPI			OMERS			Total
December 31, 2021	$	351,786		$	—		$	351,786
Net proceeds from sale of future    royalties		—			490,950			490,950
Royalty revenue		(21,692	)		—			(21,692	)
Non-cash interest expense		35,095			19,300			54,395
December 31, 2022		365,189			510,250			875,439
Royalty revenue		(20,783	)		(38,524	)		(59,307	)
Non-cash interest expense		32,235			43,200			75,435
December 31, 2023	$	376,641		$	514,926		$	891,567

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Equity

12 Months Ended

Dec. 31, 2023

Equity [Abstract]

Equity

11.Equity

At-the-Market Offerings

In May 2021, the Company entered into an Open Market Sale Agreement with Jefferies LLC, or Jefferies, pursuant to which the Company may offer and sell shares of the Company’s common stock having an aggregate offering proceeds up to $350.0 million, from time to time, in at-the-market, or ATM, offerings through Jefferies. During the year ended December 31, 2023, there were 1,175,584 shares sold under the ATM resulting in net proceeds of $53.3 million. There were no shares sold under the ATM for year ended December 31, 2022. As of December 31, 2023, the Company has sold a total of 2,225,956 shares under the ATM, resulting in net proceeds of $132.2 million.

Underwritten Public Offering

In October 2023, the Company completed an underwritten public offering in which 9,833,334 shares of common stock were sold, including the exercise in full by the underwriters of their option to purchase an additional 1,500,000 shares, at a public offering price of $30.00 per share. In connection with the offering, the Company sold to certain investors pre-funded warrants, in lieu of common stock, to purchase 1,666,722 shares of common stock at a purchase price of $29.999 per pre-funded warrant, which equals the public offering price per share of common stock less the $0.001 exercise price per share of each pre-funded warrant. The total

proceeds that the Company received from the offering were $326.5 million, net of underwriting discounts and commissions. As of December 31, 2023, none of the pre-funded warrants had been exercised.

The pre-funded warrants were classified as a component of permanent equity in the Company's Consolidated Balance Sheets as they are freestanding financial instruments that are immediately exercisable, do not embody an obligation for the Company to repurchase its own shares and permit the holders to receive a fixed number of shares of common stock upon exercise. All of the shares underlying the pre-funded warrants have been included in the weighted-average number of shares of common stock used to calculate net loss per share, basic and diluted, attributable to common stockholders because the shares may be issued for little or no consideration, are fully vested, and are exercisable after the original issuance date of the pre-funded warrants.

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Stock-Based Awards

12 Months Ended

Dec. 31, 2023

Share-Based Payment Arrangement [Abstract]

Stock-Based Awards

12.Stock-Based Awards

Equity Plan Awards

In 2014, the Company adopted the 2014 Incentive Plan, or the 2014 Plan, for the granting of stock-based awards to employees, directors, and consultants under terms and provisions established by the board of directors. The 2014 Plan had 2,250,000 shares of common stock available for future issuance at the time of its inception. The 2014 Plan provided for automatic annual increases in shares available for grant, beginning on January 1, 2015 through June 7, 2023. In June 2023, the Company adopted the 2023 Incentive Plan which had 4,500,000 shares of common stock available for future issuance at the time of its inception, plus the number of shares subject to the 2014 Plan cancelled after June 7, 2023. No further shares were granted under the 2014 Plan after June 7, 2023.In February 2021, the Company adopted the Employment Inducement Plan, or the Inducement Plan, which was subsequently amended in June 2023 to provide for a maximum of 850,000 shares available for grant under the plan. In 2014, the Company adopted the 2014 Incentive Plan, or the 2014 Plan, for the granting of stock-based awards to employees, directors, and consultants under terms and provisions established by the board of directors. Under the terms of the 2023 Plan and Inducement Plan, awards may be granted at an exercise price not less than fair market value. The exercise price of an option may not be less than the fair market value. The term of an award granted under the 2023 Plan and Inducement Plan may not exceed ten years. Typically, the vesting schedule for option grants to the employees provides that ¼ of the grant vests upon the first anniversary of the date of grant, with the remainder of the shares vesting monthly thereafter at a rate of 1/48 of the total shares subject to the option. Typically, the vesting schedule for RSU grants provides that ¼ of the grant vests upon the annual anniversary of the date of grant over the period of four years.

As of December 31, 2023, an aggregate of 19,610,125 shares of common stock have been authorized for issuance under the 2014 Plan, the 2023 Plan, and the Inducement Plan.

Stock Option Activity

The following table summarizes activity under the Company’s stock option plans and related information:

	Options Outstanding
	Number of Options			Weighted- Average Exercise Price		Weighted-Average Remaining Contractual Term (Years)	Aggregate Intrinsic Value
							(In thousands)
Outstanding — December 31, 2022		7,773,367		$	72.56	6.60	$	8,476
Options granted		2,123,256			45.05
Options exercised		(209,793	)		13.07
Options cancelled		(899,118	)		71.56
Outstanding — December 31, 2023		8,787,712			67.43	6.39		7,558
Vested and exercisable — December 31, 2023		5,415,110			73.28	4.96		1,214
Vested and expected to vest — December 31, 2023		8,461,973			67.96	6.29		6,794

The aggregate intrinsic values of options outstanding, vested and exercisable, and vested and expected to vest were calculated as the difference between the exercise price of the options and the fair value of the Company’s common stock. The total intrinsic value of options exercised during the years ended December 31, 2023, 2022, and 2021 was $4.9 million, $2.6 million, and $38.8 million, respectively. Cash received from the exercise of options was $2.7 million, $6.2 million, and $36.6 million for the years ended December 31, 2023, 2022, and 2021, respectively.

The weighted-average estimated fair value of stock options granted was $25.53, $34.77, and $70.84 per share of the Company’s common stock during the years ended December 31, 2023, 2022, and 2021, respectively. The total estimated grant date fair value of options vested during the years ended December 31, 2023, 2022, and 2021 was $59.7 million, $58.7 million, and $48.1 million, respectively.

Performance Stock Options

The following table summarizes activity under the Company’s Performance Stock Option, or PSO, plans and related information:

	PSOs Outstanding
	Number of Options			Weighted- Average Exercise Price		Weighted-Average Remaining Contractual Term (Years)		Aggregate Intrinsic Value
Outstanding — December 31, 2022		1,624,599		$	67.37		4.14	$	—
PSOs cancelled		(243,601	)		67.37
Outstanding — December 31, 2023		1,380,998			67.37		3.15		—
Vested and exercisable — December 31, 2023		117,865			67.37		3.09		—
Vested and expected to vest — December 31, 2023		983,173			67.37		3.14		—

During the year ended December 31, 2022, PSOs were granted to certain nonexecutive employees. PSOs are subject to vest only if specified operational milestones are achieved and the employees’ continued service with the Company. The Company uses the Black-Scholes method to calculate the fair value at the grant date and is recognizing stock-based compensation expense for the PSOs that are expected to vest. Stock-based compensation for PSOs is recognized over the service period, beginning in the period the Company determines it is probable that a milestone will be achieved. Forfeitures of PSOs are recognized as they occur. The Company reassesses the probability of the performance condition at each reporting period and adjusts the compensation cost based on the probability assessment. As of December 31, 2023, certain operational milestones were deemed probable of achievement. The aggregate intrinsic values of PSOs outstanding, vested and exercisable, and vested and expected to vest were calculated as the difference between the exercise price of the PSOs and the fair value of the Company’s common stock. The total estimated grant date fair value of PSOs vested during the year ended December 31, 2023, was $3.4 million. No PSOs were granted or were exercised during the year ended December 31, 2023. The weighted-average estimated fair value of PSOs granted was $28.76 during the year ended December 31, 2022.

Restricted Stock Units

The following table summarizes activity under the Company’s Restricted Stock Units, or RSU, plans and related information:

	RSUs Outstanding
	Number of Shares			Weighted- Average Grant Date Fair Value
Unvested — December 31, 2022		2,129,153		$	75.11
RSUs granted		2,447,170			44.52
RSUs vested		(738,130	)		73.99
RSUs cancelled		(394,081	)		61.22
Unvested — December 31, 2023		3,444,112			55.21

The fair value of the RSUs is determined on the grant date based on the fair value of the Company’s common stock. The fair value of the RSUs is recognized as expense ratably over the vesting period of one to four years. The total grant date fair value of the RSUs vested during the years ended December 31, 2023, 2022, and 2021 was $54.6 million, $47.1 million, and $35.5 million, respectively. The aggregate intrinsic value of the shares of the RSUs vested during the years ended December 31, 2023, 2022, and 2021 was $33.0 million, $37.8 million, and $69.9 million, respectively.

Performance Stock Units

The following table summarizes activity under the Company’s Performance Stock Units, or PSUs and related information:

	PSUs Outstanding
	Number of Shares			Weighted- Average Grant Date Fair Value
Unvested — December 31, 2022		209,230		$	98.09
PSUs granted		362,470			50.29
PSUs vested		(27,581	)		141.86
PSUs cancelled		(38,013	)		106.80
Unvested — December 31, 2023		506,106			60.82

The fair value of the PSUs is determined on the grant date based on the fair value of the Company’s common stock, except for certain PSUs with a market vesting condition, for which fair value is estimated using a Monte Carlo simulation model. PSUs are subject to vest only if certain specified criteria are achieved and the employees’ continued service with the Company. For certain PSUs, the number of PSUs that may vest are also subject to the achievement of certain specified criteria, including both performance conditions and market conditions. As of December 31, 2023, certain specified criteria were deemed probable of achievement or already achieved. Stock-based compensation for PSUs is recognized over the service period beginning in the period the Company determines it is probable that the performance criteria will be achieved. The total grant date fair value of the PSUs vested during the years ended December 31, 2023, 2022, and 2021 was $3.9 million, $1.6 million, and $9.2 million, respectively, with an aggregate intrinsic value of the shares of $1.3 million, $2.0 million and $18.9 million, respectively.

Employee Stock Purchase Plan

In January 2014, the Company adopted the 2014 Employee Stock Purchase Plan, or ESPP, which was amended and restated in June 2023. Under the ESPP, eligible employees may purchase common stock at 85% of the lesser of the fair market value of common stock on the offering date or the purchase date with a six-month look-back feature. ESPP purchases are settled with common stock from the ESPP’s previously authorized and available pool of shares. During the year ended December 31, 2023, the Company issued 195,462 shares of common stock under the ESPP. As of December 31, 2023, an aggregate of 6,609,795 shares of common stock have been authorized for future issuance on the ESPP.

Stock-Based Compensation Expense

Total stock-based compensation recognized was as follows (in thousands):

	Year Ended December 31,
	2023		2022		2021
Cost of sales	$	1,166	$	902	$	871
Research and development		74,531		74,464		59,097
Selling, general and administrative		59,516		55,002		45,011
Total stock-based compensation expense	$	135,213	$	130,368	$	104,979

Stock-based compensation of $1.9 million, $2.2 million, and $1.7 million was capitalized into inventory for the years ended December 31, 2023, 2022, and 2021, respectively. Capitalized stock-based compensation is recognized as cost of sales when the related product is sold. As of December 31, 2023, the total unrecognized compensation expense related to unvested equity awards, net of estimated forfeitures, was $219.8 million, which the Company expects to recognize over an estimated weighted-average period of 2.2 years. In determining the estimated fair value of the stock options, PSOs and ESPP, the Company uses the Black-Scholes option-pricing model and assumptions discussed below. Each of these inputs is subjective and generally requires significant judgment to determine.

Expected Term—The Company’s expected term represents the period that the Company’s stock-based awards are expected to be outstanding and is determined using the simplified method (based on the mid-point between the vesting date and the end of the contractual term).

Expected Volatility—The Company’s expected volatility is based on historical volatility over the look-back period corresponding to the expected term.

Risk-Free Interest Rate—The risk-free interest rate is based on the U.S. Treasury zero coupon issues in effect at the time of grant for periods corresponding with the expected term of option.

Expected Dividend—The Company has never paid dividends on its common stock and has no plans to pay dividends on its common stock. Therefore, the Company used an expected dividend yield of zero.

Strike price for options awards and PSOs is equal to the closing market value of our common stock on the date of grant.

The fair value of stock option awards granted was estimated at the date of grant using a Black-Scholes option-pricing model with the following weighted-average assumptions:

	Year Ended December 31,
	2023	2022	2021
Expected term (years)	6.07	6.07	6.06
Expected volatility	55%	56%	60%
Risk-free interest rate	4.2%	2.0%	1.0%
Expected dividend rate	0.0%	0.0%	0.0%

The fair value of PSOs granted was estimated at the date of grant using a Black-Scholes option-pricing model with the following weighted-average assumptions:

	Year Ended December 31,
	2022
Expected term in years	3.60
Expected volatility	57%
Risk-free interest rate	1.5%
Expected dividend rate	0.0%

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Defined Contribution Plan

12 Months Ended

Dec. 31, 2023

Defined Contribution Pension And Other Post Retirement Plan Disclosure [Abstract]

Defined Contribution Plan

13.Defined Contribution Plan

The Company sponsors a retirement plan in which substantially all of its full-time employees in the U.S. and certain other foreign countries are eligible to participate. Eligible participants may contribute a percentage of their annual compensation to this plan, subject to statutory limitations. The Company recorded $9.7 million, $9.0 million, and $5.5 million as expense related to the plan for the years ended December 31, 2023, 2022, and 2021, respectively.

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Income Taxes

12 Months Ended

Dec. 31, 2023

Income Tax Disclosure [Abstract]

Income Taxes

14.Income Taxes

The components of the Company’s loss before income taxes were as follows (in thousands):

	Year Ended December 31,
	2023		2022			2021
Domestic	$	608,166	$	703,411		$	455,314
Foreign		298		(1,686	)		(2,333	)
Total loss before income taxes	$	608,464	$	701,725		$	452,981

The components of the Company’s income tax provision were as follows (in thousands):

	Year Ended December 31,
	2023			2022			2021
Current provision for income taxes:
Federal	$	—		$	—		$	—
State		(3,187	)		6,062			(14	)
International		3,127			1,274			1,058
Total current tax provision		(60	)		7,336			1,044
Deferred tax provision:
Federal		—			—			—
State		(1,608	)		(1,640	)		—
International		(157	)		—			—
Total deferred tax provision		(1,765	)		(1,640	)		—
Total (benefit from) provision for income taxes	$	(1,825	)	$	5,696		$	1,044

The Company has incurred net operating losses since inception. The Company has not reflected any benefit of such net operating loss carryforwards in the accompanying financial statements. The Company has established a full valuation allowance against its deferred tax assets due to the uncertainty surrounding the realization of such assets.

Beginning in 2022, the Tax Cuts and Jobs Act of 2017 eliminated the right to deduct research and development expenditures for tax purposes in the period the expenses were incurred and instead requires all U.S. and foreign research and development expenditures to be amortized over five and fifteen tax years, respectively. Due to this required capitalization of research and development expenditures and the significant taxable income generated as a result of our sale of royalties in July 2022, the Company has recorded current state income tax expense of $6.1 million for the year ended December 31, 2022. For the year ended December 31, 2023, the Company recognized an income tax benefit of $4.8 million attributable to modifications in its state apportionment methodology. The Company realized no benefit for current year losses due to a full valuation allowance against the U.S. net deferred tax assets. The benefit was offset by an income tax expense of $3.0 million from foreign jurisdictions.

The effective tax rate of our provision for income taxes differs from the federal statutory rate as follows:

	Year Ended December 31,
	2023				2022				2021
Federal statutory income tax rate		21.0		%		21.0		%		21.0		%
State income taxes, net of federal benefit		0.8				(0.4	)			—
Federal tax credits		7.3				5.9				7.2
Other		(0.7	)			(0.1	)			0.5
Nondeductible permanent items		(0.3	)			(0.6	)			(0.8	)
Stock-based compensation		(1.8	)			(1.2	)			1.3
Uncertain tax positions		(1.4	)			(1.2	)			(1.4	)
Change in valuation allowance		(24.1	)			(24.0	)			(27.9	)
Foreign rate differential		(0.5	)			(0.2	)			(0.1	)
Provision for income taxes		0.3		%		(0.8	)	%		(0.2	)	%

The tax effect of temporary differences that give rise to significant portions of the deferred tax assets is presented below (in thousands):

	Year Ended December 31,
	2023			2022
Deferred tax assets:
Loss carryforwards	$	266,253		$	231,835
Tax credits		305,198			260,546
Stock options		44,795			39,784
Accruals and reserves		27,694			27,029
Fixed assets and intangibles		33,853			39,233
Liabilities for sales of future royalties		205,400			214,900
Basis difference in equity investments		8,423			8,971
Capitalized research and development costs		149,898			75,335
Other		281			3,028
Gross deferred tax assets		1,041,795			900,661
Valuation allowance		(1,035,836	)		(894,518	)
Total deferred tax assets		5,959			6,143
Deferred tax liabilities:
In-process research and development		(30,688	)		(31,667	)
Right-of-use lease assets		(5,329	)		(6,143	)
Gross deferred tax liabilities		(36,017	)		(37,810	)
Net deferred tax liabilities	$	(30,058	)	$	(31,667	)

As of December 31, 2023 and 2022, the Company had approximately $1,004.8 million and $756.6 million, respectively, of federal net operating loss carryforwards available to reduce future taxable income that will begin to expire in 2031. As of December 31, 2023 and 2022, the Company had approximately $659.9 million and $710.0 million, respectively, of state net operating loss carryforwards available to reduce future taxable income that will begin to expire in 2031.

As of December 31, 2023 and 2022, the Company had federal research tax credit carryforwards of approximately $46.9 million and $32.6 million, respectively, available to reduce future tax liabilities that will begin to expire in 2030. As of December 31, 2023 and 2022, the Company had state research credit carryforwards of $74.4 million and $59.9 million, respectively, available to reduce future tax liabilities that will be carried forward indefinitely.

As of December 31, 2023 and 2022, the Company had federal Orphan Drug Credits of $269.6 million and $239.3 million, respectively, available to reduce future tax liabilities that will begin to expire in 2031.

The Company’s ability to use net operating loss and tax credit carryforwards to reduce future taxable income and liabilities may be subject to annual limitations pursuant to Internal Revenue Code Sections 382 and 383 as a result of ownership changes in the past and future. As a result of ownership changes in 2012 and 2011, $3.6 million of federal net operating loss carryforwards, $3.6 million of state net operating loss carryforwards, and $0.2 million of federal tax credits are permanently limited. Deferred tax assets for net operating losses and tax credits have been reduced and a corresponding adjustment to the valuation allowance has been recorded.

The valuation allowance increased by $141.3 million and $193.8 million during the years ended December 31, 2023 and 2022, respectively.

Due to a change in the state tax rates, the Company recorded a net decrease to the deferred tax liability of $1.6 million with a corresponding deferred income tax benefit of $1.6 million for the year ended December 31, 2023.

The Company recorded unrecognized tax benefits for uncertainties in income taxes. A reconciliation of the Company’s unrecognized tax benefits follows (in thousands):

	December 31,
	2023		2022			2021
Balance at beginning of year	$	66,794	$	55,360		$	46,662
Additions based on tax positions related to current    year		12,562		11,316			8,542
Additions for tax positions of prior years		642		377			356
Reductions for tax positions of prior years		—		(259	)		(200	)
Balance at end of year	$	79,998	$	66,794		$	55,360

Approximately $1.3 million in unrecognized tax benefits would impact the Company’s effective tax rate if recognized. The Company has elected to include interest and penalties as a component of tax expense. For the year ended December 31, 2023, the Company recognized accrued interest and penalties of $0.2 million as a component of income tax expense. No accrued interest and penalties were recognized as a component of income tax expense during the years ended December 31, 2022 and 2021. The Company does not anticipate that the amount of existing unrecognized tax benefits will significantly increase or decrease during the next year.

It is the Company’s intention to reinvest the earnings of its non-U.S. subsidiaries in their operations. As of December 31, 2023, the Company had not made a provision for any incremental foreign withholding taxes on approximately $10.8 million of the excess of the amount of net income for financial reporting over the tax basis of investments in foreign subsidiaries that are essentially permanent in duration. If these earnings were repatriated to the U.S., the deferred tax liability associated with these temporary differences would result in a nominal amount of withholding taxes.

The Company files income tax returns in the U.S. federal, 40 state tax jurisdictions, and ten foreign countries. The federal and state income tax returns from inception to December 31, 2023 remain subject to examination.

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Commitments and Contingencies

12 Months Ended

Dec. 31, 2023

Commitments and Contingencies Disclosure [Abstract]

Commitments and Contingencies

15.Commitments and Contingencies

The Company has various manufacturing, construction, clinical, research, and other contracts with vendors in the conduct of the normal course of its business. Other than as noted below, contracts are terminable, with varying provisions regarding termination. If a contract with a specific vendor were to be terminated, the Company would only be obligated for the products or services that the Company had received at the time the termination became effective.

Manufacturing and service contract obligations primarily relate to the manufacture of inventory for our approved products, the majority of which are due in the next 12 months.

As of December 31, 2023, the aggregate payments under contractually-binding manufacturing and service agreements are as follows (in thousands):

	Year Ended December 31,
	2024		2025		Total
Manufacturing and Services	$	27,899	$	5,718	$	33,617

The terms of certain of the Company’s licenses, royalties, development and collaboration agreements, as well as other research and development activities, require the Company to pay potential future milestone payments based on product development success. The amount and timing of such obligations are unknown or uncertain. These potential obligations are further described in “Note 8. License and Research Agreements.”

See “Note 9. Leases” for lease commitments.

Contingencies

While there are no material legal proceedings the Company is aware of, the Company may become party to various claims and complaints arising in the ordinary course of business. Management does not believe that any ultimate liability resulting from any of these potential claims will have a material adverse effect on its results of operations, financial position, or liquidity. However, management cannot give any assurance regarding the ultimate outcome of these claims, and their resolution could be material to operating results for any particular period, depending upon the level of income for the period.

Guarantees and Indemnifications

The Company indemnifies each of its directors and officers for certain events or occurrences, subject to certain limits, while the director or officer is or was serving at the Company’s request in such capacity, as permitted under Delaware law and in accordance with its certificate of incorporation and bylaws. The term of the indemnification period lasts as long as a director or officer may be subject to any proceeding arising out of acts or omissions of such director and officer in such capacity. The maximum amount of potential future indemnification is unlimited; however, the Company currently holds director liability insurance. This insurance allows the transfer of risk associated with the Company’s exposure and may enable it to recover a portion of any future amounts paid. The Company believes that the fair value of these indemnification obligations is minimal. Accordingly, it has not recognized any liabilities relating to these obligations for any period presented.

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Related Party Transaction

12 Months Ended

Dec. 31, 2023

Related Party Transactions [Abstract]

Related Party Transaction

16.Related Party Transaction

In July 2022, the Company entered into an agreement with a non-profit foundation in which two members of the Company’s board of directors, including the Company’s Chief Executive Officer, also serve as board members of the foundation, whereby an aggregate $1.0 million contribution is being paid to the foundation over a four-year period, beginning in the third quarter of 2022, to support rare disease education and awareness. As a result, the Company recorded $0.3 million and $0.3 million as research and development expense for this agreement for the years ended December 31, 2023 and 2022, respectively.

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Net Loss per Share

12 Months Ended

Dec. 31, 2023

Earnings Per Share [Abstract]

Net Loss per Share

17.Net Loss per Share

The following table sets forth the computation of the basic and diluted net loss per share during the years ended December 31, 2023, 2022, and 2021 (in thousands, except share and per share data):

	Year Ended December 31,
	2023			2022			2021
Numerator:
Net loss	$	(606,639	)	$	(707,421	)	$	(454,025	)
Denominator:
Weighted-average shares used to compute net loss per    share, basic and diluted		73,543,862			69,914,225			67,795,540
Net loss per share, basic and diluted	$	(8.25	)	$	(10.12	)	$	(6.70	)

The following weighted-average outstanding common stock equivalents were excluded from the computation of diluted net loss per share for the periods presented because including them would have been antidilutive:

	Year Ended December 31,
	2023		2022		2021
Options to purchase common stock,     restricted stock units, and performance stock units		14,152,286		11,290,935		8,214,063
Employee stock purchase plan		8,450		7,581		3,511
		14,160,736		11,298,516		8,217,574

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Accumulated Other Comprehensive Income (Loss)

12 Months Ended

Dec. 31, 2023

Other Comprehensive Income (Loss), Net of Tax [Abstract]

Accumulated Other Comprehensive Income (Loss)

18.Accumulated Other Comprehensive Income (Loss)

Total accumulated other comprehensive income (loss) consisted of the following (in thousands):

	Year Ended December 31,
	2023			2022
Cumulative foreign currency translation adjustment	$	(606	)	$	(845	)
Unrealized gain (loss) on securities available-for-sale		1,253			(5,728	)
Total accumulated other comprehensive income (loss)	$	647		$	(6,573	)

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Summary of Significant Accounting Policies (Policies)

12 Months Ended

Dec. 31, 2023

Accounting Policies [Abstract]

Basis of Consolidation

Basis of Consolidation

The Consolidated Financial Statements include the accounts of Ultragenyx Pharmaceutical Inc. and its wholly owned subsidiaries. All intercompany balances and transactions have been eliminated.

Use of Estimates

Use of Estimates

The accompanying Consolidated Financial Statements have been prepared in accordance with U.S. generally accepted accounting principles, or GAAP. The preparation of the Consolidated Financial Statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, disclosure of contingent liabilities and the reported amounts of expenses in the Consolidated Financial Statements and the accompanying notes. On an ongoing basis, management evaluates its estimates, including those related to clinical trial accruals, fair value of assets and liabilities, income taxes, stock-based compensation, revenue recognition, and the liabilities for sales of future royalties. Management bases its estimates on historical experience and on various other market-specific and relevant assumptions that management believes to be reasonable under the circumstances. Actual results could differ from those estimates.

Cash, Cash Equivalents, and Restricted Cash

Cash, Cash Equivalents, and Restricted Cash

The Company considers all highly liquid investments with original maturities of three months or less from the date of purchase to be cash equivalents. Cash equivalents consist primarily of amounts invested in money market accounts.

Restricted cash primarily consists of money market accounts used as collateral for the Company’s obligations under its facility leases and the gene therapy building construction project.

The following table provides a reconciliation of cash, cash equivalents, and restricted cash reported within the Consolidated Balance Sheets that sum to the total of the same such amounts shown in the Consolidated Statements of Cash Flows (in thousands):

	December 31,
	2023		2022		2021
Cash and cash equivalents	$	213,584	$	132,944	$	307,584
Restricted cash included in other current assets		2,008		862		—
Restricted cash included in other non-current assets		3,807		3,795		2,001
Total cash, cash equivalents, and restricted cash     shown in the statements of cash flows	$	219,399	$	137,601	$	309,585

Marketable Debt Securities

Marketable Debt Securities

All marketable debt securities have been classified as “available-for-sale” and are carried at estimated fair value as determined based upon quoted market prices or pricing models for similar securities. Management determines the appropriate classification of its investments at the time of purchase and reevaluates such designation as of each balance sheet date. Investments with a maturity of one year or less from the balance sheet date are reported as current marketable debt securities and investments with a maturity of greater than one year from the balance sheet date are reported as non-current marketable debt securities. Unrealized gains and losses are excluded from earnings and are reported as a component of comprehensive loss. Realized gains and losses and declines in fair value judged to be other than temporary, if any, on available-for-sale securities are included in other income (expense). The cost of securities sold is based on the specific-identification method. Interest on investments is included in interest income.

Equity Investments

Equity Investments

The Company records investments in equity securities, other than equity method investments, at fair market value, if the fair value is readily determinable. Equity securities with no readily determinable fair values are recorded using the measurement alternative of cost adjusted for observable price changes in orderly transactions for identical or similar investments of the same issuer less impairment, if any. Investments in equity securities are recorded in Equity investments on the Company's Consolidated Balance Sheets. Unrealized gains and losses are reported in Change in fair value of equity investments on the Company’s Consolidated Statements of Operations. The Company regularly reviews its non-marketable equity securities for indicators of impairment.

Concentration of Credit Risk, Credit Losses, and Other Risks and Uncertainties

Concentration of Credit Risk, Credit Losses, and Other Risks and Uncertainties

Financial instruments that potentially subject the Company to a concentration of credit risk consist of cash, cash equivalents, and investments. The Company’s cash, cash equivalents, and investments are held by financial institutions that management believes are of high credit quality. The Company’s investment policy limits investments to fixed income securities denominated and payable in U.S. dollars such as U.S. government obligations, money market instruments and funds, corporate bonds, commercial paper, and asset-backed securities and places restrictions on maturities and concentrations by type and issuer. Such deposits may, at times, exceed federally insured limits. The Company has not experienced any losses on its deposits of cash and cash equivalents and its accounts are monitored by management to mitigate risk. The Company is exposed to credit risk in the event of default by the financial institutions holding its cash and cash equivalents, corporate issuers, and other financial instruments, to the extent recorded in the Consolidated Balance Sheets.

The Company is exposed to credit losses primarily through receivables from customers and collaborators and through its available-for-sale debt securities. For trade receivables and other instruments, the Company uses a forward-looking expected loss model that generally results in the earlier recognition of allowances for losses. For available-for-sale debt securities with unrealized losses, the losses are recognized as allowances rather than as reductions in the amortized cost of the securities.

The Company’s expected loss allowance methodology for the receivables is developed using historical collection experience, current and future economic market conditions, a review of the current aging status and financial condition of the entities. Specific allowance amounts are established to record the appropriate allowance for customers that have a higher probability of default. Balances are written off when determined to be uncollectible. The Company’s expected loss allowance methodology for the debt securities is developed by reviewing the extent of the unrealized loss, the size, term, geographical location, and industry of the issuer, the issuers’ credit ratings and any changes in those ratings, as well as reviewing current and future economic market conditions and the issuers’ current status and financial condition. There was no allowance for losses on available-for-sale debt securities which were attributable to credit risk for the years ended December 31, 2023 and 2022.

The Company is dependent on third-party manufacturers to supply products for research and development activities in its programs. In particular, the Company relies and expects to continue to rely on a small number of manufacturers to supply it with its requirements for the active pharmaceutical ingredients and formulated drugs related to these programs. These programs could be adversely affected by a significant interruption in the supply of active pharmaceutical ingredients and formulated drugs.

Inventory

Inventory

The Company values inventory at the lower of cost and net realizable value and determines the cost of inventory using the average-cost method. The Company expenses costs associated with the manufacture of product candidates prior to regulatory approval. Inventories consist of currently approved products. The Company periodically reviews its inventories for excess amounts or obsolescence and writes down obsolete or otherwise unmarketable inventory to its estimated net realizable value. Management determines excess inventory based on expected future demand. Estimates related to future demand are sensitive to significant inputs and assumptions such as acceptance by patients and physicians and the availability of formulary coverage and adequate reimbursement from private third-party payers for the product.

Property, Plant, and Equipment

Property, Plant, and Equipment

Property, plant, and equipment are stated at cost, less accumulated depreciation and amortization. Depreciation and amortization is computed using the straight-line method over the estimated useful lives of the respective assets. Depreciation and amortization begins when the asset is placed in service. Interest costs incurred during the construction of major capital projects are capitalized until the underlying asset is ready to be placed in service. Maintenance and repairs are charged to operations as incurred. Upon sale or retirement of assets, the cost and related accumulated depreciation or amortization are removed from the balance sheet and the resulting gain or loss, if any, is reflected in operations. See “Note 4. Balance Sheet Components” for further disclosure on the useful lives of property, plant, and equipment.

Intangible Assets

Intangible Assets

Finite-lived intangibles consist of contractual payments made for certain milestones achieved with collaboration partners. The contractual payments are recorded as intangible assets and are amortized over their estimated useful lives. The Company reviews its definite-lived intangible assets when events or circumstances may indicate that the carrying value of these assets is not recoverable and exceeds their fair value. The Company measures fair value based on the estimated future undiscounted cash flows associated with these assets in addition to other assumptions and projections that the Company deems to be reasonable and supportable.

Indefinite-lived intangibles consist of acquired in-process research and development, or IPR&D. IPR&D assets represent capitalized incomplete research projects that the Company acquired through business combinations. Such assets are initially measured at their acquisition date fair values and are tested for impairment annually and whenever events or changes in circumstances indicate that the carrying amount may not be recoverable. When development of the project is complete, which generally occurs when regulatory approval to market a product is obtained, the associated assets will be deemed finite-lived and will be amortized over a period that best reflects the economic benefits provided by these assets.

If it is determined that an intangible asset becomes impaired, the carrying value is written down to its fair value with the related impairment charge recognized in Consolidated Statements of Operations in the period in which the impairment occurs. The Company has not recorded any impairments of intangible assets to date.

Goodwill

Goodwill

Goodwill represents the excess of purchase price over fair value of net assets acquired in a business combination and is not amortized. Goodwill is subject to impairment testing at least annually during the fourth quarter or when a triggering event occurs that could indicate a potential impairment. If it is determined that the goodwill becomes impaired, the carrying value is written down to its fair value with the related impairment charge recognized in Consolidated Statements of Operations in the period in which the impairment occurs. The Company has not recorded any impairments of goodwill.

Impairment of Long-Lived Assets

Impairment of Long-Lived Assets

The Company evaluates its long-lived assets, including property and equipment, for impairment whenever events or changes in circumstances indicate that the carrying value of these assets may not be recoverable. Recoverability of these assets is measured by comparison of the carrying amount of each asset to the future undiscounted cash flows expected to result from the use of the asset and its eventual disposition. If the asset is considered to be impaired, the amount of any impairment is measured as the difference between the carrying value and the fair value of the impaired asset. The Company has not recorded material impairment of any long-lived assets.

Accruals of Research and Development Costs

Accruals of Research and Development Costs

The Company records accruals for estimated costs of research, preclinical and clinical studies and manufacturing development. These costs are a significant component of the Company’s research and development expenses. A substantial portion of the Company’s ongoing research and development activities are conducted by third-party service providers, including contract research organizations. The Company accrues the costs incurred under its agreements with these third parties based on actual work completed in accordance with agreements established with these third parties. The Company determines the actual costs through obtaining information from external service providers as to the progress or stage of completion of the services and the agreed-upon fee to be paid for such services.

Revenue Recognition

Revenue Recognition

Product Sales

The Company sells its approved products through a limited number of distributors. Under ASC 606, revenue from product sales is recognized at the point in time when control is transferred to these distributors. The Company also recognizes revenue from sales of certain products on a “named patient” basis, which are allowed in certain countries prior to the commercial approval of the product. Prior to recognizing revenue, the Company makes estimates of the transaction price, including any variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Product sales are recorded net of estimated government-mandated rebates and chargebacks, estimated product returns, and other deductions.

Provisions for returns and other adjustments are provided for in the period the related revenue is recorded, as estimated by management. These reserves are based on estimates of the amounts earned or to be claimed on the related sales and are reviewed periodically and adjusted as necessary. The Company’s estimates of government mandated rebates, chargebacks, estimated product returns, and other deductions depends on the identification of key customer contract terms and conditions, as well as estimates of sales volumes to different classes of payors. If actual results vary, the Company may need to adjust these estimates, which could have a material effect on earnings in the period of the adjustment.

Collaboration, License, and Royalty Revenue

The Company has certain license and collaboration agreements that are within the scope of Accounting Standards Codification, or ASC, 808, Collaborative Agreements, which provides guidance on the presentation and disclosure of collaborative arrangements. Generally, the classification of the transactions under the collaborative arrangements is determined based on the nature of contractual terms of the arrangement, along with the nature of the operations of the participants. The Company records its share of collaboration revenue, net of transfer pricing related to net sales in the period in which such sales occur, if the Company is considered as an agent in the arrangement. The Company is considered an agent when the collaboration partner controls the product before transfer to the customers and has the ability to direct the use of and obtain substantially all of the remaining benefits from the product. Funding received related to research and development services and commercialization costs is generally classified as a reduction of research and development expenses and selling, general and administrative expenses, respectively, in the Consolidated Statements of Operations, because the provision of such services for collaborative partners are not considered to be part of the Company’s ongoing major or central operations.

The Company utilizes certain information from its collaboration partners to record collaboration revenue, including revenue from the sale of the product, associated reserves on revenue, and costs incurred for development and sales activities. For the periods covered in the financial statements presented, there have been no material changes to prior period estimates of revenues and expenses. The Company also records royalty revenues under certain of the Company’s license or collaboration agreements in exchange for license of intellectual property.

The Company sold the right to receive certain royalty payments from net sales of Crysvita in certain territories to RPI Finance Trust, or RPI, an affiliate of Royalty Pharma, and to OCM LS23 Holdings LP, an investment vehicle for Ontario Municipal Employees Retirement System, or OMERS, as further described in “Note 10. Liabilities for Sales of Future Royalties.” The Company records the royalty revenue from the net sales of Crysvita in the applicable territories on a prospective basis as non-cash royalty revenue in the Consolidated Statements of Operations over the term of the applicable arrangement.

The terms of the Company’s collaboration and license agreements may contain multiple performance obligations, which may include licenses and research and development activities. The Company evaluates these agreements under ASC 606, Revenue from Contracts with Customers, or ASC 606, to determine the distinct performance obligations. The Company analogizes to ASC 606 for the accounting for distinct performance obligations for which there is a customer relationship. Prior to recognizing revenue, the Company makes estimates of the transaction price, including variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Total consideration may include nonrefundable upfront license fees, payments for research and development activities, reimbursement of certain third-party costs, payments based upon the achievement of specified milestones, and royalty payments based on product sales derived from the collaboration.

If there are multiple distinct performance obligations, the Company allocates the transaction price to each distinct performance obligation based on its relative standalone selling price. The standalone selling price is generally determined based on the prices charged to customers or using expected cost-plus margin. The Company estimates the efforts needed to complete the performance obligations and recognizes revenue by measuring the progress towards complete satisfaction of the performance obligations using input measures.

Deferred Compensation Plan

Deferred Compensation Plan

The Company maintains a nonqualified deferred compensation plan whereby certain employees and members of the board of directors are able to defer certain equity awards and other compensation. Amounts deferred are invested into shares of the Company's common stock, mutual funds, and other investment options. The plan complies with the provisions of Section 409A of the Internal Revenue Code. All of the various mutual funds held in the plan are classified as trading securities and recorded at fair value in other non-current assets in the Consolidated Balance Sheets with changes in fair value recognized as earnings in the period they occur. The short-term portion of the corresponding liability for the plan is included in accrued expenses. The long-term portion of the liability is included in other non-current liabilities in the Consolidated Balance Sheets. Certain equity awards deferred under the plan are required to be settled through the issuance of Company stock. These awards are recorded as treasury stock and deferred compensation obligation within stockholders’ equity.

Leases

Leases

Lease agreements are evaluated to determine whether an arrangement is or contains a lease in accordance with ASC 842, Leases. The Company determines if an arrangement includes a lease at inception. Right-of-use lease assets and lease liabilities are

recognized based on the present value of the future minimum lease payments over the lease term at the commencement date. The right-of-use lease asset includes any lease payments made and excludes lease incentives. Incremental borrowing rate is used in determining the present value of future payments. The Company applies a portfolio approach to the property leases to apply an incremental borrowing rate to leases with similar lease terms. The lease terms may include options to extend or terminate the lease. The Company recognizes the options to extend the lease as part of the right-of-use lease assets and lease liabilities only if it is reasonably certain that the option would be exercised. Lease expense for minimum lease payments is recognized on a straight-line basis over the non-cancelable lease term. The Company has elected to not separate lease and non-lease components. See “Note 9. Leases” for further disclosure.

Comprehensive Loss

Comprehensive Loss

Comprehensive loss is the change in stockholders’ equity from transactions and other events and circumstances other than those resulting from investments by stockholders and distributions to stockholders. The Company’s other comprehensive loss is comprised of unrealized gains and losses on investments in available-for-sale securities and foreign currency translation adjustments.

Research and Development

Research and Development

Research and development costs are expensed as incurred and consist of salaries and benefits, stock-based compensation expense, lab supplies and facility costs, as well as fees paid to other nonemployees and entities that conduct certain research and development activities on the Company’s behalf. Amounts incurred in connection with license agreements are also included in research and development expense. Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are deferred. The deferred amounts are expensed as the related goods are delivered or the services are performed.

Stock-Based Compensation

Stock-Based Compensation

Stock-based awards issued to employees, including stock options, performance stock options, or PSOs, restricted stock units, or RSUs, and performance stock units, or PSUs are recorded at fair value as of the grant date and recognized as expense on a straight-line basis over the employee’s requisite service period (generally the vesting period). PSOs and PSUs vest only if certain specified criteria are achieved and the employees’ continued service requirements are met; therefore, the expense recognition occurs when the likelihood of the PSOs and PSUs being earned is deemed probable. Stock compensation expense on awards expected to vest is recognized net of estimated forfeitures.

Income Taxes

Income Taxes

The Company uses the liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are determined based on the differences between the financial reporting and the tax bases of assets and liabilities and are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. The Company must then assess the likelihood that the resulting deferred tax assets will be realized. A valuation allowance is provided when it is more likely than not that some portion or all of a deferred tax asset will not be realized. Due to the Company’s lack of earnings history, the net deferred tax assets have been fully offset by a valuation allowance.

In conjunction with the acquisition of Dimension Therapeutics, Inc., or Dimension, a deferred tax liability was recorded reflecting the tax impact of the difference between the book basis and tax basis of acquired IPR&D. Such deferred income tax liability is not used to offset deferred tax assets when analyzing the Company’s valuation allowance as the acquired IPR&D is considered to have an indefinite life until the Company completes or abandons development of the acquired IPR&D.

The Company recognizes benefits of uncertain tax positions if it is more likely than not that such positions will be sustained upon examination based solely on their technical merits, as the largest amount of benefit that is more likely than not to be realized upon the ultimate settlement. The Company’s policy is to recognize interest and penalties related to the underpayment of income taxes as a component of income tax expense or benefit. To date, there have been no interest or penalties charged in relation to the unrecognized tax benefits.

Foreign Currency

Foreign Currency

Assets and liabilities of non-U.S. subsidiaries that operate in a local currency environment, where the local currency is the functional currency, are translated to U.S. dollars at exchange rates in effect at the balance sheet date, with the resulting translation adjustments directly recorded to a separate component of accumulated other comprehensive loss. Income and expense accounts are translated at average exchange rates for the period. Transactions which are not in the functional currency of the entity are remeasured into the functional currency and gains or losses resulting from the remeasurement recorded in other income (expense).

Net Loss per Share

Net Loss per Share

Basic net loss per share is calculated by dividing the net loss by the weighted-average number of shares of common stock outstanding during the period, without consideration for common stock equivalents. Shares of common stock into which pre-funded warrants may be exercised are considered outstanding for the purposes of computing basic net loss per share because the shares may be issued for little or no consideration, are fully vested and are exercisable after the original issuance date. Diluted net loss per share is the same as basic net loss per share, since the effects of potentially dilutive securities are antidilutive. In periods when we have incurred a net loss, options and warrants to purchase common stock are considered common stock equivalents, but have been excluded from the calculation of diluted net loss per share, as their effect is antidilutive.

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Summary of Significant Accounting Policies (Tables)

12 Months Ended

Dec. 31, 2023

Accounting Policies [Abstract]

Summary of Reconciliation of Cash, Cash Equivalents and Restricted Cash

The following table provides a reconciliation of cash, cash equivalents, and restricted cash reported within the Consolidated Balance Sheets that sum to the total of the same such amounts shown in the Consolidated Statements of Cash Flows (in thousands):

	December 31,
	2023		2022		2021
Cash and cash equivalents	$	213,584	$	132,944	$	307,584
Restricted cash included in other current assets		2,008		862		—
Restricted cash included in other non-current assets		3,807		3,795		2,001
Total cash, cash equivalents, and restricted cash     shown in the statements of cash flows	$	219,399	$	137,601	$	309,585

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Fair Value Measurements (Tables)

12 Months Ended

Dec. 31, 2023

Fair Value Disclosures [Abstract]

Summary of Financial Assets Measured on Recurring Basis

The following tables set forth the fair value of the Company’s financial assets remeasured on a recurring basis based on the three-tier fair value hierarchy (in thousands):

	December 31, 2023
	Level 1		Level 2		Level 3		Total
Financial Assets:
Money market funds	$	162,289	$	—	$	—	$	162,289
Certificates of deposit and time deposits		—		17,986		—		17,986
Corporate bonds		—		215,166		—		215,166
Commercial paper		—		20,620		—		20,620
Asset-backed securities		—		2,712		—		2,712
U.S. Government Treasury and agency securities		57,437		259,605		—		317,042
Investment in Solid common stock		3,204		—		—		3,204
Deferred compensation assets		—		10,220		—		10,220
Total financial assets	$	222,930	$	526,309	$	—	$	749,239
Financial Liabilities:
Deferred compensation liabilities	$	—	$	10,365	$	—	$	10,365

	December 31, 2022
	Level 1		Level 2		Level 3		Total
Financial Assets:
Money market funds	$	102,847	$	—	$	—	$	102,847
Certificates of deposit and time deposits		—		25,972		—		25,972
Corporate bonds		—		427,598		—		427,598
Commercial paper		—		135,393		—		135,393
Asset-backed securities		—		11,980		—		11,980
U.S. Government Treasury and agency securities		27,645		129,345		—		156,990
Debt securities in government-sponsored entities		—		15,855		—		15,855
Investment in Solid common stock		2,807		—		—		2,807
Deferred compensation assets		—		4,575		—		4,575
Total financial assets	$	133,299	$	750,718	$	—	$	884,017
Financial Liabilities:
Deferred compensation liabilities	$	—	$	4,657	$	—	$	4,657

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Balance Sheet Components (Tables)

12 Months Ended

Dec. 31, 2023

Investments, Debt and Equity Securities [Abstract]

Summary of Cash Equivalents and Marketable Debt Securities Classified as Available For Sale Securities

The fair values of cash equivalents and marketable debt securities classified as available-for-sale securities consisted of the following (in thousands):

	December 31, 2023
			Gross Unrealized
	Amortized Cost		Gains		Losses			Estimated Fair Value
Money market funds	$	162,289	$	—	$	—		$	162,289
Certificates of deposit and time deposits		17,986		—		—			17,986
Corporate bonds		214,792		711		(337	)		215,166
Commercial paper		20,620		—		—			20,620
Asset-backed securities		2,715		—		(3	)		2,712
U.S. Government Treasury and agency securities		316,160		982		(100	)		317,042
Total	$	734,562	$	1,693	$	(440	)	$	735,815

	December 31, 2022
			Gross Unrealized
	Amortized Cost		Gains		Losses			Estimated Fair Value
Money market funds	$	102,847	$	—	$	—		$	102,847
Certificates of deposit and time deposits		25,972		—		—			25,972
Corporate bonds		432,211		87		(4,700	)		427,598
Commercial paper		135,393		—		—			135,393
Asset-backed securities		12,002		—		(22	)		11,980
U.S. Government Treasury and agency securities		157,933		320		(1,263	)		156,990
Debt securities in government-sponsored entities		16,005		—		(150	)		15,855
Total	$	882,363	$	407	$	(6,135	)	$	876,635

Summary of Inventory

Inventory consists of the following (in thousands):

	December 31,
	2023		2022
Work-in-process	$	18,859	$	17,486
Finished goods		15,110		9,280
Total inventory	$	33,969	$	26,766

Summary of Property, Plant and Equipment, Net

Property, plant, and equipment, net consists of the following (in thousands):

		December 31,
	Useful life (years)	2023			2022
Building	20-30	$	181,356		$	2,798
Leasehold improvements	Shorter of lease term or estimated useful life		58,683			43,941
Research and development equipment	5		56,347			50,291
Furniture and office equipment	5		6,419			5,540
Computer equipment and software	3-5		16,196			13,876
Manufacturing equipment	5-15		37,297			570
Land	Not applicable		16,619			16,619
Construction-in-progress	Not applicable		867			189,448
Other	Varies by asset		183			24
Property, plant, and equipment, gross			373,967			323,107
Less: accumulated depreciation			(83,401	)		(63,381	)
Property, plant, and equipment, net		$	290,566		$	259,726

Summary of Accrued Liabilities

Accrued liabilities consists of the following (in thousands):

	December 31,
	2023		2022
Research, clinical study, and manufacturing expenses	$	65,326	$	73,558
Payroll and related expenses		82,936		78,938
Other		48,224		52,182
Total accrued liabilities	$	196,486	$	204,678

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Intangible Assets, net (Table)

12 Months Ended

Dec. 31, 2023

Intangible Assets, Net (Excluding Goodwill) [Abstract]

Summary of Company's Intangible Assets

The Company's intangible assets were as follows:

	December 31, 2023
	Gross Carrying Amount		Weighted-Average Life (Years)		Accumulated Amortization			Net Carrying Amount
Indefinite-lived intangibles	$	129,000		—	$	—		$	129,000
Finite-lived intangibles		44,775		9.6		(7,504	)		37,271
Total intangible assets	$	173,775		—	$	(7,504	)	$	166,271

	December 31, 2022
	Gross Carrying Amount		Weighted-Average Life (Years)		Accumulated Amortization			Net Carrying Amount
Indefinite-lived intangibles	$	129,000		—	$	—		$	129,000
Finite-lived intangibles		34,775		9.9		(3,670	)		31,105
Total intangible assets	$	163,775		—	$	(3,670	)	$	160,105

Schedule of Expected Amortization of the Intangible Assets

The expected amortization of the intangible assets, as of December 31, 2023, for each of the next five years and thereafter is as follows:

2024	$	4,903
2025		4,903
2026		4,903
2027		4,462
2028		4,022
Thereafter		14,078
Total	$	37,271

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Revenue (Tables)

12 Months Ended

Dec. 31, 2023

Revenue from Contract with Customer [Abstract]

Summary of Disaggregation of Total Revenues

The following table disaggregates total revenues from external customers by product sales, royalty revenue, and collaboration and license revenue (in thousands):

	Year Ended December 31,
	2023		2022		2021
Product sales:
Crysvita	$	75,697	$	42,678	$	21,422
Mepsevii		30,441		20,637		16,035
Dojolvi		70,633		55,612		39,560
Evkeeza		3,642		—		—
Total product sales		180,413		118,927		77,017
Crysvita royalty revenue		182,652		21,692		17,951
Collaboration and license revenue:
Crysvita collaboration revenue in Profit-Share Territory		69,705		215,024		171,198
Crysvita royalty revenue in European Territory		—		—		244
Daiichi Sankyo		1,479		7,686		84,996
Total collaboration and license revenue		71,184		222,710		256,438
Total revenues	$	434,249	$	363,329	$	351,406

The following table disaggregates total revenues based on geographic location (in thousands):

	Year Ended December 31,
	2023		2022		2021
North America	$	307,149	$	281,088	$	301,110
Latin America		77,342		44,711		23,636
Europe		47,534		36,369		26,660
Japan		2,224		1,161		—
Total revenues	$	434,249	$	363,329	$	351,406

Schedule of Sales-Related Accruals and Allowances

The following table presents the activity and ending balances for sales-related accruals and allowances (in thousands):

	Year Ended December 31,
	2023			2022			2021
Balance of product sales reserve at beginning of year	$	11,487		$	7,181		$	3,913
Provisions		18,761			13,525			9,586
Payments		(12,746	)		(9,613	)		(6,120	)
Adjustments		(473	)		394			(198	)
Balance of product sales reserve at end of year	$	17,029		$	11,487		$	7,181

Summary of Changes in Contract Liabilities

The following table presents changes in the contract liabilities for the years ended December 31, 2023 and 2022 (in thousands):

	Year Ended December 31,
	2023			2022
Balance of contract liabilities at beginning of period	$	1,479		$	9,076
Additions		—			89
Deductions		(1,479	)		(7,686	)
Balance of contract liabilities at end of period, net	$	—		$	1,479

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License and Research Agreements (Tables)

12 Months Ended

Dec. 31, 2023

Share of Collaboration and Royalty Revenue Related to Crysvita

Total Crysvita revenue was as follows (in thousands):

	Year Ended December 31,
	2023		2022		2021
Revenue in profit-share territory:
Collaboration revenue	$	69,705	$	215,024	$	171,198
Royalty revenue		113,288		—		—
Non-cash royalty revenue		48,581		—		—
Total revenue in Profit-Share Territory		231,574		215,024		171,198
Product sales		75,697		42,678		21,422
Royalty revenue in European Territory		—		—		244
Non-cash royalty revenue in European Territories		20,783		21,692		17,951
Total Crysvita revenue	$	328,054	$	279,394	$	210,815

Royalty Revenue for Sales in the European Territory

KKC has the commercial responsibility for Crysvita in the European Territory. In December 2019, the Company sold its right to receive royalty payments based on sales in the European Territory to Royalty Pharma, effective January 1, 2020, as further described in Note 10. Prior to the Company’s sale of the royalty, the Company received a royalty of up to 10% on net sales in the European Territory, which was recognized as the underlying sales occur. Beginning in 2020, the Company records the royalty revenue as non-cash royalty revenues. The Company records this revenue as royalty revenue.

Schedule Of Collaboration Cost Sharing and Payments

These amounts were recognized in the Company’s Statements of Operations in connection with the collaboration agreement with KKC as follows (in thousands):

	Year Ended December 31,
	2023			2022			2021
Research and development	$	(6,510	)	$	(15,974	)	$	(21,657	)
Selling, general and administrative	$	(17,199	)	$	(37,217	)	$	(32,629	)
Cost of sales	$	18,476		$	13,250		$	6,701

Solid Biosciences, Inc.

Schedule of Changes in Fair Value of Investment in Securities

The changes in the fair value of the Company’s investment in Solid’s common stock were as follows (in thousands):

	Solid Common Stock
December 31, 2021	$	13,695
Change in fair value		(10,888	)
December 31, 2022		2,807
Change in fair value		397
December 31, 2023	$	3,204

Arcturus

Schedule of Changes in Fair Value of Equity Investment

The changes in the fair value of the Company’s equity investment in Arcturus were as follows (in thousands):

	Arcturus Common Stock
December 31, 2021	$	18,505
Change in fair value		(8,411	)
Sale of shares		(10,094	)
December 31, 2022	$	—

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Leases (Tables)

12 Months Ended

Dec. 31, 2023

Lessee Disclosure [Abstract]

Summary of Components of Lease Expense

The components of lease expense were as follows (in thousands):

	Year Ended December 31,
	2023		2022		2021
Operating lease expense	$	12,883	$	11,775	$	11,209
Variable lease expense		5,272		4,785		4,142
Financing:
Amortization		203		343		310
Interest expense		—		37		58
Total	$	18,358	$	16,940	$	15,719

Schedule of Maturities of Lease Liabilities and the Reconciliation of Lease Liabilities

The following table summarizes maturities of lease liabilities and the reconciliation of lease liabilities as of December 31, 2023:

Year Ending December 31,	Operating
2024	$	16,234
2025		11,932
2026		8,430
2027		5,867
2028		5,887
Thereafter		6,009
Total future lease payments		54,359
Less: Amount representing interest		(11,190	)
Present value of future lease payments		43,169
Less: Lease liabilities, current		(12,595	)
Lease liabilities, non-current	$	30,574

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Liabilities for Sales of Future Royalties (Tables)

12 Months Ended

Dec. 31, 2023

Deferred Revenue Disclosure [Abstract]

Schedule of Activity Within Liability for Sale of Future Royalties

The following table shows the activity within the liability account (in thousands):

	Liabilities for Sales of Future Royalties
	RPI			OMERS			Total
December 31, 2021	$	351,786		$	—		$	351,786
Net proceeds from sale of future    royalties		—			490,950			490,950
Royalty revenue		(21,692	)		—			(21,692	)
Non-cash interest expense		35,095			19,300			54,395
December 31, 2022		365,189			510,250			875,439
Royalty revenue		(20,783	)		(38,524	)		(59,307	)
Non-cash interest expense		32,235			43,200			75,435
December 31, 2023	$	376,641		$	514,926		$	891,567

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Stock-Based Awards (Tables)

12 Months Ended

Dec. 31, 2023

Share Based Compensation Arrangement By Share Based Payment Award [Line Items]

Summary of Activity Under Stock Option Plans Including 2011 Plan, 2014 Plan and 2023 Plan

Stock Option Activity

The following table summarizes activity under the Company’s stock option plans and related information:

	Options Outstanding
	Number of Options			Weighted- Average Exercise Price		Weighted-Average Remaining Contractual Term (Years)	Aggregate Intrinsic Value
							(In thousands)
Outstanding — December 31, 2022		7,773,367		$	72.56	6.60	$	8,476
Options granted		2,123,256			45.05
Options exercised		(209,793	)		13.07
Options cancelled		(899,118	)		71.56
Outstanding — December 31, 2023		8,787,712			67.43	6.39		7,558
Vested and exercisable — December 31, 2023		5,415,110			73.28	4.96		1,214
Vested and expected to vest — December 31, 2023		8,461,973			67.96	6.29		6,794

Summary of Stock-Based Compensation Expense

Total stock-based compensation recognized was as follows (in thousands):

	Year Ended December 31,
	2023		2022		2021
Cost of sales	$	1,166	$	902	$	871
Research and development		74,531		74,464		59,097
Selling, general and administrative		59,516		55,002		45,011
Total stock-based compensation expense	$	135,213	$	130,368	$	104,979

Fair Value of Stock Option Awards Granted Estimated Using Black-Scholes Option-Pricing Model

The fair value of stock option awards granted was estimated at the date of grant using a Black-Scholes option-pricing model with the following weighted-average assumptions:

	Year Ended December 31,
	2023	2022	2021
Expected term (years)	6.07	6.07	6.06
Expected volatility	55%	56%	60%
Risk-free interest rate	4.2%	2.0%	1.0%
Expected dividend rate	0.0%	0.0%	0.0%

The fair value of PSOs granted was estimated at the date of grant using a Black-Scholes option-pricing model with the following weighted-average assumptions:

	Year Ended December 31,
	2022
Expected term in years	3.60
Expected volatility	57%
Risk-free interest rate	1.5%
Expected dividend rate	0.0%

Restricted Stock Units

Share Based Compensation Arrangement By Share Based Payment Award [Line Items]

Summary of Activity Under Stock Units from 2014 Plan

The following table summarizes activity under the Company’s Restricted Stock Units, or RSU, plans and related information:

	RSUs Outstanding
	Number of Shares			Weighted- Average Grant Date Fair Value
Unvested — December 31, 2022		2,129,153		$	75.11
RSUs granted		2,447,170			44.52
RSUs vested		(738,130	)		73.99
RSUs cancelled		(394,081	)		61.22
Unvested — December 31, 2023		3,444,112			55.21

Performance Stock Units

Share Based Compensation Arrangement By Share Based Payment Award [Line Items]

Summary of Activity Under Stock Units from 2014 Plan

The following table summarizes activity under the Company’s Performance Stock Units, or PSUs and related information:

	PSUs Outstanding
	Number of Shares			Weighted- Average Grant Date Fair Value
Unvested — December 31, 2022		209,230		$	98.09
PSUs granted		362,470			50.29
PSUs vested		(27,581	)		141.86
PSUs cancelled		(38,013	)		106.80
Unvested — December 31, 2023		506,106			60.82

Performance Stock Options [Member]

Share Based Compensation Arrangement By Share Based Payment Award [Line Items]

Summary of Activity Under Stock Option Plans Including 2011 Plan, 2014 Plan and 2023 Plan

The following table summarizes activity under the Company’s Performance Stock Option, or PSO, plans and related information:

	PSOs Outstanding
	Number of Options			Weighted- Average Exercise Price		Weighted-Average Remaining Contractual Term (Years)		Aggregate Intrinsic Value
Outstanding — December 31, 2022		1,624,599		$	67.37		4.14	$	—
PSOs cancelled		(243,601	)		67.37
Outstanding — December 31, 2023		1,380,998			67.37		3.15		—
Vested and exercisable — December 31, 2023		117,865			67.37		3.09		—
Vested and expected to vest — December 31, 2023		983,173			67.37		3.14		—

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Income Taxes (Tables)

12 Months Ended

Dec. 31, 2023

Income Tax Disclosure [Abstract]

Components of Company's Loss Before Income Taxes

The components of the Company’s loss before income taxes were as follows (in thousands):

	Year Ended December 31,
	2023		2022			2021
Domestic	$	608,166	$	703,411		$	455,314
Foreign		298		(1,686	)		(2,333	)
Total loss before income taxes	$	608,464	$	701,725		$	452,981

Components of Company's Income Tax Provision

The components of the Company’s income tax provision were as follows (in thousands):

	Year Ended December 31,
	2023			2022			2021
Current provision for income taxes:
Federal	$	—		$	—		$	—
State		(3,187	)		6,062			(14	)
International		3,127			1,274			1,058
Total current tax provision		(60	)		7,336			1,044
Deferred tax provision:
Federal		—			—			—
State		(1,608	)		(1,640	)		—
International		(157	)		—			—
Total deferred tax provision		(1,765	)		(1,640	)		—
Total (benefit from) provision for income taxes	$	(1,825	)	$	5,696		$	1,044

Effective Tax Rate of Provision for Income Taxes from Federal Statutory Rate

The effective tax rate of our provision for income taxes differs from the federal statutory rate as follows:

	Year Ended December 31,
	2023				2022				2021
Federal statutory income tax rate		21.0		%		21.0		%		21.0		%
State income taxes, net of federal benefit		0.8				(0.4	)			—
Federal tax credits		7.3				5.9				7.2
Other		(0.7	)			(0.1	)			0.5
Nondeductible permanent items		(0.3	)			(0.6	)			(0.8	)
Stock-based compensation		(1.8	)			(1.2	)			1.3
Uncertain tax positions		(1.4	)			(1.2	)			(1.4	)
Change in valuation allowance		(24.1	)			(24.0	)			(27.9	)
Foreign rate differential		(0.5	)			(0.2	)			(0.1	)
Provision for income taxes		0.3		%		(0.8	)	%		(0.2	)	%

Schedule of Tax Effect of Temporary Differences to Significant Portions of Deferred Tax Assets

The tax effect of temporary differences that give rise to significant portions of the deferred tax assets is presented below (in thousands):

	Year Ended December 31,
	2023			2022
Deferred tax assets:
Loss carryforwards	$	266,253		$	231,835
Tax credits		305,198			260,546
Stock options		44,795			39,784
Accruals and reserves		27,694			27,029
Fixed assets and intangibles		33,853			39,233
Liabilities for sales of future royalties		205,400			214,900
Basis difference in equity investments		8,423			8,971
Capitalized research and development costs		149,898			75,335
Other		281			3,028
Gross deferred tax assets		1,041,795			900,661
Valuation allowance		(1,035,836	)		(894,518	)
Total deferred tax assets		5,959			6,143
Deferred tax liabilities:
In-process research and development		(30,688	)		(31,667	)
Right-of-use lease assets		(5,329	)		(6,143	)
Gross deferred tax liabilities		(36,017	)		(37,810	)
Net deferred tax liabilities	$	(30,058	)	$	(31,667	)

Unrecognized Tax Benefits

A reconciliation of the Company’s unrecognized tax benefits follows (in thousands):

	December 31,
	2023		2022			2021
Balance at beginning of year	$	66,794	$	55,360		$	46,662
Additions based on tax positions related to current    year		12,562		11,316			8,542
Additions for tax positions of prior years		642		377			356
Reductions for tax positions of prior years		—		(259	)		(200	)
Balance at end of year	$	79,998	$	66,794		$	55,360

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Commitments and Contingencies (Tables)

12 Months Ended

Dec. 31, 2023

Commitments and Contingencies Disclosure [Abstract]

Summary of Aggregate Payments under Contractually Binding Manufacturing and Service Agreements

As of December 31, 2023, the aggregate payments under contractually-binding manufacturing and service agreements are as follows (in thousands):

	Year Ended December 31,
	2024		2025		Total
Manufacturing and Services	$	27,899	$	5,718	$	33,617

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Net Loss per Share (Tables)

12 Months Ended

Dec. 31, 2023

Earnings Per Share [Abstract]

Computation of Basic and Diluted Net Loss per Share

The following table sets forth the computation of the basic and diluted net loss per share during the years ended December 31, 2023, 2022, and 2021 (in thousands, except share and per share data):

	Year Ended December 31,
	2023			2022			2021
Numerator:
Net loss	$	(606,639	)	$	(707,421	)	$	(454,025	)
Denominator:
Weighted-average shares used to compute net loss per    share, basic and diluted		73,543,862			69,914,225			67,795,540
Net loss per share, basic and diluted	$	(8.25	)	$	(10.12	)	$	(6.70	)

Outstanding Shares of Common Stock Equivalents Excluded from Computation of Diluted Net Loss per Share

The following weighted-average outstanding common stock equivalents were excluded from the computation of diluted net loss per share for the periods presented because including them would have been antidilutive:

	Year Ended December 31,
	2023		2022		2021
Options to purchase common stock,     restricted stock units, and performance stock units		14,152,286		11,290,935		8,214,063
Employee stock purchase plan		8,450		7,581		3,511
		14,160,736		11,298,516		8,217,574

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Accumulated Other Comprehensive Income (Loss) (Tables)

12 Months Ended

Dec. 31, 2023

Other Comprehensive Income (Loss), Net of Tax [Abstract]

Schedule of Total Accumulated Other Comprehensive Income (Loss)

Total accumulated other comprehensive income (loss) consisted of the following (in thousands):

	Year Ended December 31,
	2023			2022
Cumulative foreign currency translation adjustment	$	(606	)	$	(845	)
Unrealized gain (loss) on securities available-for-sale		1,253			(5,728	)
Total accumulated other comprehensive income (loss)	$	647		$	(6,573	)

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Organization and Basis of Presentation - Additional Information (Details)	12 Months Ended
	Dec. 31, 2023 Segment
Organization And Nature Of Business [Line Items]
Number of reportable segments	1

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Summary of Significant Accounting Policies - Summary of Reconciliation of Cash, Cash Equivalents and Restricted Cash (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Accounting Policies [Abstract]
Cash and cash equivalents	$ 213,584	$ 132,944	$ 307,584
Restricted cash included in other current assets	$ 2,008	$ 862	$ 0
Restricted Cash and Cash Equivalents, Current, Asset, Statement of Financial Position [Extensible List]	Other assets	Other assets	Other assets
Restricted cash included in other non-current assets	$ 3,807	$ 3,795	$ 2,001
Restricted Cash and Cash Equivalents, Noncurrent, Asset, Statement of Financial Position [Extensible List]	Other assets	Other assets	Other assets
Total cash, cash equivalents, and restricted cash shown in the statements of cash flows	$ 219,399	$ 137,601	$ 309,585	$ 726,294

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Summary of Significant Accounting Policies - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Accounting Policies [Abstract]
Allowance for doubtful accounts	$ 0	$ 0
Unrecognized tax benefits related to interest or penalties	$ 0

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Fair Value Measurements - Summary of Financial Assets Measured on Recurring Basis (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	$ 749,239	$ 884,017
Level 1
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	222,930	133,299
Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	526,309	750,718
Money Market Funds
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	162,289	102,847
Money Market Funds | Level 1
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	162,289	102,847
Asset-backed Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	2,712	11,980
Asset-backed Securities | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	2,712	11,980
Certificates of Deposit and Time Deposits
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	17,986	25,972
Certificates of Deposit and Time Deposits | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	17,986	25,972
Corporate Bonds
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	215,166	427,598
Corporate Bonds | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	215,166	427,598
Commercial Paper
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	20,620	135,393
Commercial Paper | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	20,620	135,393
U.S. Government Treasury and Agency Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	317,042	156,990
U.S. Government Treasury and Agency Securities | Level 1
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	57,437	27,645
U.S. Government Treasury and Agency Securities | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	259,605	129,345
Debt Securities in Government Sponsored Entities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value		15,855
Debt Securities in Government Sponsored Entities | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value		15,855
Investments in Solid Common Stock
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	3,204	2,807
Investments in Solid Common Stock | Level 1
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	3,204	2,807
Deferred compensation assets
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	10,220	4,575
Deferred compensation assets | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	10,220	4,575
Deferred compensation liabilities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	10,365	4,657
Deferred compensation liabilities | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	$ 10,365	$ 4,657

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Fair Value Measurements - Additional Information (Details) - USD ($) $ in Millions	Dec. 31, 2023	Dec. 31, 2022
Short-Term Debt [Member]
Schedule Of Available For Sale Securities [Line Items]
Deferred compensation liabilities	$ 0.2	$ 0.0
Long-Term Debt [Member]
Schedule Of Available For Sale Securities [Line Items]
Deferred compensation liabilities	$ 10.1	$ 4.7

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Balance Sheet Components - Summary of Cash Equivalents and Marketable Debt Securities Classified as Available For Sale Securities (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	$ 734,562	$ 882,363
Gross Unrealized Gains	1,693	407
Gross Unrealized Losses	(440)	(6,135)
Estimated Fair Value	735,815	876,635
Money Market Funds
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	162,289	102,847
Estimated Fair Value	162,289	102,847
Asset-backed Securities
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	2,715	12,002
Gross Unrealized Gains	0	0
Gross Unrealized Losses	(3)	(22)
Estimated Fair Value	2,712	11,980
Certificates of Deposit and Time Deposits
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	17,986	25,972
Estimated Fair Value	17,986	25,972
Corporate Bonds
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	214,792	432,211
Gross Unrealized Gains	711	87
Gross Unrealized Losses	(337)	(4,700)
Estimated Fair Value	215,166	427,598
Commercial Paper
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	20,620	135,393
Estimated Fair Value	20,620	135,393
U.S. Government Treasury and Agency Securities
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	316,160	157,933
Gross Unrealized Gains	982	320
Gross Unrealized Losses	(100)	(1,263)
Estimated Fair Value	$ 317,042	156,990
Debt Securities in Government Sponsored Entities
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost		16,005
Gross Unrealized Losses		(150)
Estimated Fair Value		$ 15,855

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Balance Sheet Components - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Schedule Of Available For Sale Securities [Line Items]
Depreciation expense	$ 22.2	$ 15.0	$ 12.9
Maximum
Schedule Of Available For Sale Securities [Line Items]
Available-for-sale securities remaining contractual maturities	3 years

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Balance Sheet Components - Summary of Inventory (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Inventory, Net [Abstract]
Work-in-process	$ 18,859	$ 17,486
Finished goods	15,110	9,280
Total inventory	$ 33,969	$ 26,766

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Balance Sheet Components - Summary of Property, Plant and Equipment, Net (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	$ 373,967	$ 323,107
Less accumulated depreciation	(83,401)	(63,381)
Property, plant and equipment, net	290,566	259,726
Building
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	$ 181,356	$ 2,798
Building | Minimum
Property Plant And Equipment [Line Items]
Property, plant and equipment, estimated useful lives (years)	20 years	20 years
Building | Maximum
Property Plant And Equipment [Line Items]
Property, plant and equipment, estimated useful lives (years)	30 years	30 years
Leasehold Improvements
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	$ 58,683	$ 43,941
Property, plant and equipment, estimated useful lives	us-gaap:UsefulLifeShorterOfTermOfLeaseOrAssetUtilityMember	us-gaap:UsefulLifeShorterOfTermOfLeaseOrAssetUtilityMember
Research and Development Equipment
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	$ 56,347	$ 50,291
Property, plant and equipment, estimated useful lives (years)	5 years	5 years
Furniture and Office Equipment
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	$ 6,419	$ 5,540
Property, plant and equipment, estimated useful lives (years)	5 years	5 years
Computer Equipment and Software
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	$ 16,196	$ 13,876
Computer Equipment and Software | Minimum
Property Plant And Equipment [Line Items]
Property, plant and equipment, estimated useful lives (years)	3 years	3 years
Computer Equipment and Software | Maximum
Property Plant And Equipment [Line Items]
Property, plant and equipment, estimated useful lives (years)	5 years	5 years
Manufacturing Equipment
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	$ 37,297	$ 570
Manufacturing Equipment | Minimum
Property Plant And Equipment [Line Items]
Property, plant and equipment, estimated useful lives (years)	5 years	5 years
Manufacturing Equipment | Maximum
Property Plant And Equipment [Line Items]
Property, plant and equipment, estimated useful lives (years)	15 years	15 years
Land
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	$ 16,619	$ 16,619
Construction-in-progress
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	867	189,448
Other
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	$ 183	$ 24

XML

Balance Sheet Components - Summary of Accrued Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Payables and Accruals [Abstract]
Research, clinical study, and manufacturing expenses	$ 65,326	$ 73,558
Payroll and related expenses	82,936	78,938
Other	48,224	52,182
Total accrued liabilities	$ 196,486	$ 204,678

XML

Intangible Assets, Net - Additional Information (Details) 1 - USD ($) $ in Millions	Dec. 31, 2023	Dec. 31, 2022
IPR&D Assets
Indefinite-Lived Intangible Assets [Line Items]
Business combination recognized intangible assets	$ 129.0	$ 129.0

XML

Intangible Assets, Net - Additional Information (Details) - USD ($) $ in Millions	1 Months Ended	12 Months Ended
	Jan. 31, 2022	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Finite Lived Intangible Assets Line Items
upfront payment	$ 30.0
Acquired Finite Lived Intangible Assets Weighted Average Useful Life		10 years
Regulatory milestone payments achieved		$ 10.0
Cost of sales
Finite Lived Intangible Assets Line Items
Costs of sales related to amortization of intangible asset		$ 3.8	$ 3.2	$ 0.3
Dimension
Finite Lived Intangible Assets Line Items
Intangible assets, remaining amortization period		5 years 8 months 12 days
Regulatory milestone payments achieved		$ 4.8

XML

Intangible Assets, Net - Summary of Company's Intangible Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Schedule of Finite and Indefinite Lived Intangible Assets [Line Items]
Intangible assets - Gross carrying amount	$ 173,775	$ 163,775
Intangible assets - Accumulated Amortization	(7,504)	(3,670)
Intangible assets - Net Carrying Amount	166,271	160,105
Indefinite-lived Intangible Assets
Schedule of Finite and Indefinite Lived Intangible Assets [Line Items]
Intangible assets - Gross carrying amount	129,000	129,000
Intangible assets - Net Carrying Amount	129,000	129,000
Finite lived intangible assets
Schedule of Finite and Indefinite Lived Intangible Assets [Line Items]
Intangible assets - Gross carrying amount	$ 44,775	$ 34,775
Intangible assets - Weighted Average Life	9 years 7 months 6 days	9 years 10 months 24 days
Intangible assets - Accumulated Amortization	$ (7,504)	$ (3,670)
Intangible assets - Net Carrying Amount	$ 37,271	$ 31,105

XML

Intangible Assets, Net - Schedule of Expected Amortization of the Intangible Assets (Details) $ in Thousands	Dec. 31, 2023 USD ($)
Intangible Assets, Net (Excluding Goodwill) [Abstract]
2024	$ 4,903
2025	4,903
2026	4,903
2027	4,462
2028	4,022
Thereafter	14,078
Total	$ 37,271

XML

Revenue - Summary of Disaggregation of Total Revenues from Customers (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Disaggregation Of Revenue [Line Items]
Total revenues	$ 434,249	$ 363,329	$ 351,406
Collaboration and license
Disaggregation Of Revenue [Line Items]
Total revenues	71,184	222,710	256,438
Collaboration and license | Crysvita
Disaggregation Of Revenue [Line Items]
Total revenues	69,705	215,024	171,198
Collaboration and license | Crysvita | Royalty Revenue in European Territory
Disaggregation Of Revenue [Line Items]
Total revenues	0	0	244
Collaboration and license | Daiichi Sankyo
Disaggregation Of Revenue [Line Items]
Total revenues	1,479	7,686	84,996
Product Revenue
Disaggregation Of Revenue [Line Items]
Total revenues	180,413	118,927	77,017
Product Revenue | Crysvita
Disaggregation Of Revenue [Line Items]
Total revenues	75,697	42,678	21,422
Product Revenue | Mepsevii
Disaggregation Of Revenue [Line Items]
Total revenues	30,441	20,637	16,035
Product Revenue | Dojolvi
Disaggregation Of Revenue [Line Items]
Total revenues	70,633	55,612	39,560
Product Revenue | Evkeeza
Disaggregation Of Revenue [Line Items]
Total revenues	3,642	0	0
Royalty revenue
Disaggregation Of Revenue [Line Items]
Total revenues	182,652	21,692	17,951
Royalty revenue | Crysvita
Disaggregation Of Revenue [Line Items]
Total revenues	$ 182,652	$ 21,692	$ 17,951

XML

Revenue - Summary of Disaggregation of Total Revenues (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Disaggregation Of Revenue [Line Items]
Total revenues	$ 434,249	$ 363,329	$ 351,406
North America
Disaggregation Of Revenue [Line Items]
Total revenues	307,149	281,088	301,110
Latin America
Disaggregation Of Revenue [Line Items]
Total revenues	77,342	44,711	23,636
Europe
Disaggregation Of Revenue [Line Items]
Total revenues	47,534	36,369	26,660
Japan
Disaggregation Of Revenue [Line Items]
Total revenues	$ 2,224	$ 1,161	$ 0

XML

Revenue - Schedule of Sales-Related Accruals and Allowances (Details) - Product sales - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Disaggregation Of Revenue [Line Items]
Balance of product sales reserve at beginning of year	$ 11,487	$ 7,181	$ 3,913
Provisions	18,761	13,525	9,586
Payments	(12,746)	(9,613)	(6,120)
Adjustments	(473)	394	(198)
Balance of product sales reserve at end of year	$ 17,029	$ 11,487	$ 7,181

XML

Revenue - Summary of Changes in Contract Liabilities (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Disaggregation of Revenue [Abstract]
Balance of contract liabilities at beginning of period	$ 1,479	$ 9,076
Additions	0	89
Deductions	(1,479)	(7,686)
Balance of contract liabilities at end of period, net	$ 0	$ 1,479

XML

Revenue - Additional Information (Details)	Dec. 31, 2023	Dec. 31, 2022
Customer One
Disaggregation of Revenue [Line Items]
Percentage of gross accounts receivable balance	53.00%	68.00%

XML

GeneTx Acquisition - Additional Information (Details) - USD ($) $ in Thousands	1 Months Ended	12 Months Ended
	Jul. 31, 2022	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Business Acquisition [Line Items]
Acquired in-process research and development		$ 0	$ 75,033	$ 0
GeneTx [Member]
Business Acquisition [Line Items]
Business acquisition, consideration transferred	$ 75,000
Regulatory Approval Milestones	85,000
Outstanding Cash and Cash Equivalents Acquired	15,600
Amount on adjustments for working capital and transaction expenses	600
Payments to Acquire Businesses, Gross	91,200
GeneTx [Member] | Maximum
Business Acquisition [Line Items]
Future contingent milestone payments	190,000
Additional Milestone Payments	30,000
Commercial Milestone Payment	75,000
Texas A&M University [Member] | Maximum
Business Acquisition [Line Items]
Future contingent milestone payments	23,500
Annual License Fee Payment	$ 2,000
In-process Research and Development [Member] | GeneTx [Member]
Business Acquisition [Line Items]
Acquired in-process research and development			$ 75,000

XML

License and Research Agreements - Kyowa Kirin Co., Ltd. - Additional Information (Details) - Kyowa Kirin Collaboration - License Agreement - USD ($) $ in Millions		12 Months Ended	113 Months Ended
	Jul. 01, 2022	Dec. 31, 2023	Dec. 31, 2022
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Profit loss sharing percentage on net sales		30.00%	35.00%
Minimum
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Tiered double-digit revenue share percentage entitled to receive		20.00%
Maximum
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Tiered double-digit revenue share percentage entitled to receive		30.00%
Other Current Assets
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
License agreement other receivables		$ 1.1	$ 6.4
Profit Share Revenue
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
License agreement accounts receivable		39.2	27.5
Commercial And Development Activity Reimbursements [Member]
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
License agreement accrued liabilities		$ 5.3	$ 3.1
Profit Share Territory
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Remaining profit or loss share percentage on commercializing products		50.00%
Percentage of right to receive royalty payments on net sales	30.00%
Royalty Revenue in European Territory
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Percentage of royalty on net sales receives		10.00%

XML

License and Research Agreements - Saint Louis University - Additional Information (Details) $ in Millions	12 Months Ended
	Dec. 31, 2023 USD ($)
Saint Louis University
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Milestone payments paid	$ 0.1

XML

License and Research Agreements - Baylor Research Institute - Additional Information (Details) - Baylor Research Institute - Development Milestones - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Future contingent milestone payments	$ 7.5
Research and Development Expense
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Contingent milestone payment	$ 0.0	$ 2.5

XML

License and Research Agreements - REGENXBIO, Inc. - Additional Information (Details) - REGENXBIO, Inc. - USD ($) $ in Millions	1 Months Ended	12 Months Ended
	Mar. 31, 2020	Dec. 31, 2023
Option and License Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Future contingent milestone payments		$ 9.0
Option and license agreement description		The Company also has an option and license agreement with REGENX under which the Company has an exclusive, sublicensable, worldwide license to make, have made, use, import, sell, and offer for sale licensed products to treat Wilson disease and CDKL5 deficiency.
Annual maintenance fee for each option exercised		$ 0.1
License Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Future contingent milestone payments		14.0
Upfront payment for in-process research and development expense	$ 7.0
Annual fees payable		$ 0.1

XML

License and Research Agreements - University of Pennsylvania - Additional Information (Details) - University of Pennsylvania School of Medicine (Penn) $ in Millions	Dec. 31, 2023 USD ($)
Research Collaboration and License Agreement Development Milestones
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Future contingent milestone payments	$ 5.0
Research Collaboration and License Agreement Commercial Milestones
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Future contingent milestone payments	$ 25.0

XML

License and Research Agreements - Arcturus Therapeutics Holdings Inc. - Additional Information (Details) $ / shares in Units, $ in Millions	1 Months Ended			12 Months Ended
	May 31, 2020 USD ($) shares	Jun. 30, 2019 USD ($) DiseaseTarget $ / shares shares	Oct. 31, 2015 USD ($)	Dec. 31, 2022 $ / shares shares	Dec. 31, 2021 USD ($)	Dec. 31, 2023 $ / shares
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Common stock. per share | $ / shares				$ 0.001		$ 0.001
Arcturus Therapeutics Holdings Inc
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Milestone payments received					$ 1.0
Upfornt cash payment paid		$ 6.0
Common stock purchased | shares		2,400,000
Common stock shares sold | shares				500,000
Common stock. per share | $ / shares		$ 10		$ 20.39
Business acquisition, consideration transferred		$ 30.0
Additional option to purchase common stock | shares		600,000
Additional option to purchase common stock value per share | $ / shares		$ 16
Number of shares purchased on exercise of common stock option | shares	600,000
Purchase price of shares purchased on exercise of common stock option	$ 9.6
Number of common stock held | shares				0
Arcturus Therapeutics Holdings Inc | Maximum
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Number of disease targets | DiseaseTarget		12
Regulatory milestone payments			$ 24.5
Commercial milestone payments			$ 45.0

XML

License and Research Agreements - Daiichi Sankyo - Additional Information (Details) - USD ($) $ / shares in Units, $ in Millions	1 Months Ended		3 Months Ended	12 Months Ended
	Jun. 30, 2020	Mar. 31, 2020	Mar. 31, 2020	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Collaborative Arrangement, Revenue Not from Contract with Customer, Statement of Income or Comprehensive Income [Extensible Enumeration]				Revenue
Daiichi Sankyo
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Deferred Revenue balance				$ 0.0	$ 1.5
Deferred Revenue Recognized				1.5	$ 7.7	$ 85.0
License and Technology Access Agreement | Daiichi Sankyo
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Deferred Revenue balance				25.0
Upfront payment received				125.0
License and Technology Access Agreement | Daiichi Sankyo | Licenses Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Revenue recognized				$ 183.3
Stock Purchase Agreement | Daiichi Sankyo
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Issuance of common stock in connection with license agreement, net of issuance costs, shares		1,243,913
Proceeds from issuance of common stock in connection with license agreement			$ 75.0
Issuance of common stock in connection with license agreement, net of issuance costs			$ 55.3
Stock price		$ 44.43	$ 44.43
Premium from stock purchase agreement			$ 19.7
Sublicense Agreement | Daiichi Sankyo
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront payment received	$ 8.0

XML

License and Research Agreements - Mereo - Additional Information (Details) - USD ($) $ in Thousands	1 Months Ended	12 Months Ended
	Jan. 31, 2021	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Research and development		$ 648,449	$ 705,789	$ 497,153
License and Collaboration Agreement | Mereo
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Research and development		$ 9,000	$ 0	$ 50,000
Payments made under agreement	$ 50,000
License and Collaboration Agreement | Maximum | Mereo
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Future contingent milestone payments	$ 254,000

XML

License and Research Agreements - Regeneron - Additional Information (Details) - USD ($) $ in Thousands	1 Months Ended	12 Months Ended
	Jan. 31, 2022	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Regulatory milestone payments achieved		$ 10,000
Cost of sales		45,209	$ 28,320	$ 16,008
Regeneron Pharmaceuticals Inc
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Upfront payments of collaboration	$ 30,000
Regulatory milestone payments achieved		10,000
Development costs		7,600	7,300	$ 0
Eligible future milestone payments	$ 63,000
Accrued collaboration payables		10,600	$ 6,800
Cost of sales		$ 700
Maximum | Regeneron Pharmaceuticals Inc
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Profit loss sharing percentage on net sales		40.00%
Minimum | Regeneron Pharmaceuticals Inc
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Profit loss sharing percentage on net sales	20.00%

XML

License and Research Agreements - Abeona - Additional Information (Details) - Abeona - USD ($) $ in Millions	1 Months Ended	12 Months Ended
	May 31, 2022	Dec. 31, 2023	Dec. 31, 2022
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Other costs			$ 0.0
Development and transition costs			$ 3.1
Maximum
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Eligible future milestone payments		$ 1.0
License and Collaboration Agreement
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Percentage of royalty on net sales receives		10.00%
Commercial milestone payments	$ 30.0

XML

License and Research Agreements - Solid Biosciences, Inc. - Additional Information (Details) $ in Thousands	1 Months Ended		12 Months Ended
	Oct. 31, 2022 shares	Oct. 31, 2020 USD ($) shares	Dec. 31, 2020 USD ($)	Dec. 31, 2023 USD ($)	Dec. 31, 2022 USD ($)
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Common stock investment value				$ 82	$ 70
Solid Biosciences, Inc.
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Remaining consideration paid			$ 13,200
Business acquisition, consideration transferred			$ 40,000
Common stock investment value		$ 26,800
Description of the stock split	In October 2022, Solid announced a 1 for 15 reverse stock split. After the split, the Company held 521,719 shares of Solid's common stock.
stock split conversion ratio	1
Number of common shares held after split | shares	521,719
Collaboration Agreement | Solid Biosciences, Inc.
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Number of common stock purchased | shares		7,825,797
Aggregate purchase price		$ 40,000
Maximum | Collaboration and License Agreement | Solid Biosciences, Inc.
Collaborative Arrangement and Arrangement Other than Collaborative [Line Items]
Development milestone payments		25,000
Regulatory milestone payments		65,000
Commercial milestone payments		$ 165,000

XML

License and Research Agreements - Share of Collaboration and Royalty Revenue Related to Crysvita (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	$ 434,249	$ 363,329	$ 351,406
Collaboration and Royalty | Kyowa Kirin Collaboration
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	328,054	279,394	210,815
Collaboration and Royalty | Kyowa Kirin Collaboration | Profit Share Territory
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	231,574	215,024	171,198
Royalty revenue
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	182,652	21,692	17,951
Royalty revenue | Kyowa Kirin Collaboration | Profit Share Territory
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	113,288	0	0
Royalty revenue | Kyowa Kirin Collaboration | Royalty Revenue in European Territory
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	0	0	244
Product sales
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	180,413	118,927	77,017
Product sales | Kyowa Kirin Collaboration
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	75,697	42,678	21,422
Collaboration Revenue | Kyowa Kirin Collaboration | Profit Share Territory
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	69,705	215,024	171,198
Non-cash royalty revenue | Kyowa Kirin Collaboration | Profit Share Territory
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	48,581	0	0
Non-cash royalty revenue | Kyowa Kirin Collaboration | Royalty Revenue in European Territory
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	$ 20,783	$ 21,692	$ 17,951

XML

License and Research Agreements - Schedule of Collaboration Cost Sharing and Payments (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Cost Sharing Payments [Line Items]
Cost of sales	$ 45,209	$ 28,320	$ 16,008
Kyowa Kirin Collaboration
Cost Sharing Payments [Line Items]
Research and development	(6,510)	(15,974)	(21,657)
Selling, general and administrative	(17,199)	(37,217)	(32,629)
Cost of sales	$ 18,476	$ 13,250	$ 6,701

XML

License and Research Agreements - Schedule of Changes in Fair Value of Equity Investment (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Common stock, Beginning balance	$ 884,017
Common stock, Ending balance	749,239	$ 884,017
Arcturus | Common Stock
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Common stock, Beginning balance	$ 0	18,505
Common stock, Change in fair value		(8,411)
Common stock, Sale of shares		(10,094)
Common stock, Ending balance		$ 0

XML

License and Research Agreements - Schedule of Changes in Fair Value of Investment in Securities (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Common stock, Beginning balance	$ 884,017
Common stock, Ending balance	749,239	$ 884,017
Common Stock | Solid Biosciences, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Common stock, Beginning balance	2,807	13,695
Common stock, Change in fair value	397	(10,888)
Common stock, Ending balance	$ 3,204	$ 2,807

XML

Leases - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Lessee Disclosure [Abstract]
Operating lease extension details	multiple renewal periods
Operating lease, existence of option to extend	true
Operating lease expiry term	2029
Operating Lease, Right-of-Use Asset, Statement of Financial Position [Extensible Enumeration]	Other Assets, Noncurrent	Other Assets, Noncurrent
Right-of-use lease assets	$ 23.9	$ 26.0
Cash paid for measurement of operating lease liabilities	$ 13.4	$ 13.1	$ 11.8
Operating lease weighted average remaining lease term	4 years 6 months	3 years
Financing lease weighted average remaining lease term		2 years 9 months 18 days
Operating lease weighted average discount rate	9.60%	6.70%
Financing lease weighted average discount rate		5.10%

XML

Leases - Summary of Components of Lease Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Lease, Cost [Abstract]
Operating lease expense	$ 12,883	$ 11,775	$ 11,209
Variable lease expense	5,272	4,785	4,142
Financing:
Amortization	203	343	310
Interest expense	0	37	58
Total	$ 18,358	$ 16,940	$ 15,719

XML

Leases - Schedule of Maturities of Lease Liabilities and the Reconciliation of Lease Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Operating
2024	$ 16,234
2025	11,932
2026	8,430
2027	5,867
2028	5,887
Thereafter	6,009
Total future lease payments	54,359
Less: Amount representing interest	(11,190)
Present value of future lease payments	43,169
Less: Lease liabilities, current	$ (12,595)
Operating Lease, Liability, Statement of Financial Position [Extensible List]	Less: Lease liabilities, current
Lease liabilities, non-current	$ 30,574
Operating Lease, Liability, Statement of Financial Position [Extensible List]	Non-current lease liability
Future Minimum Lease Payments - Operating and Financing Leases
Less: Lease liabilities, current	$ (12,595)	$ (11,779)
Finance Lease, Liability, Current, Statement of Financial Position [Extensible Enumeration]	Less: Lease liabilities, current
Non-current lease liability	$ 30,574	$ 19,814
Finance Lease, Liability, Noncurrent, Statement of Financial Position [Extensible Enumeration]	Non-current lease liability

XML

Liabilities for Sales of Future Royalties - Additional Information (Details) - USD ($) $ in Thousands	1 Months Ended		12 Months Ended			49 Months Ended
	Jul. 31, 2022	Dec. 31, 2019	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2023
Liability For Sale Of Future Royalties [Line Items]
Proceeds from the sale of future royalties, net			$ 0	$ 490,950	$ 0
Non-cash collaboration royalty revenue			$ 69,364	21,692	$ 17,951
RPI Finance Trust (RPI)
Liability For Sale Of Future Royalties [Line Items]
Proceeds from the sale of future royalties, net				0
OMERS
Liability For Sale Of Future Royalties [Line Items]
Proceeds from the sale of future royalties, net				$ 490,950
Royalty Purchase Agreement
Liability For Sale Of Future Royalties [Line Items]
Profit loss sharing percentage on net sales	30.00%
Royalty Purchase Agreement | RPI Finance Trust (RPI)
Liability For Sale Of Future Royalties [Line Items]
Proceeds from sale of future royalties		$ 320,000
Royalty payment termination description			The agreement with RPI will automatically terminate, and the payment of royalties to RPI will cease, in the event aggregate royalty payments received by RPI are equal to or greater than $608.0 million prior to December 31, 2030, or in the event aggregate royalty payments received by RPI are less than $608.0 million prior to December 31, 2030, or when aggregate royalty payments received by RPI are equal to $800.0 million.
Royalties transaction costs net		5,800
Proceeds from the sale of future royalties, net		314,200
Effective annual interest rate			6.20%			6.20%
Non-cash collaboration royalty revenue						$ 73,400
Royalty Purchase Agreement | OMERS
Liability For Sale Of Future Royalties [Line Items]
Proceeds from sale of future royalties	$ 500,000
Royalty payment termination description	In July 2022, the Company entered into a Royalty Purchase Agreement with OMERS. Pursuant to the agreement, OMERS paid $500.0 million to the Company in consideration for the right to receive 30% of the future royalty payments due to the Company from KKC based on net sales of Crysvita in the U.S. and Canada under the terms of the KKC Collaboration Agreement. The calculation of royalty payments to OMERS is based on net sales of Crysvita beginning in April 2023 and will expire upon the earlier of the date on which aggregate payments received by OMERS equals $725.0 million or the date the final royalty payment is made to the Company under the KKC Collaboration Agreement.
Royalty agreement termination threshold amount	$ 725,000
Payment from sale of future royalties	500,000
Royalties transaction costs net	$ 9,100
Proceeds from the sale of future royalties, net		$ 491,000
Effective annual interest rate			7.80%			7.80%
Non-cash collaboration royalty revenue						$ 8,600
Royalty Purchase Agreement | Minimum | RPI Finance Trust (RPI)
Liability For Sale Of Future Royalties [Line Items]
Royalty agreement termination threshold amount			$ 608,000			608,000
Royalty Purchase Agreement | Maximum | RPI Finance Trust (RPI)
Liability For Sale Of Future Royalties [Line Items]
Royalty agreement termination threshold amount			$ 800,000			$ 800,000

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Liabilities for Sales of Future Royalties - Schedule of Activity Within Liability Related to Sale of Future Royalties (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Liability For Sale Of Future Royalties [Line Items]
Liability for sale of future royalties at beginning of year	$ 875,439	$ 351,786
Net proceeds from sale of future royalties	0	490,950	$ 0
Royalty revenue	(59,307)	(21,692)
Non-cash interest expense	75,435	54,395
Liability for sale of future royalties at end of year	891,567	875,439	351,786
RPI Finance Trust (RPI)
Liability For Sale Of Future Royalties [Line Items]
Liability for sale of future royalties at beginning of year	365,189	351,786
Net proceeds from sale of future royalties		0
Royalty revenue	(20,783)	(21,692)
Non-cash interest expense	32,235	35,095
Liability for sale of future royalties at end of year	376,641	365,189	351,786
OMERS
Liability For Sale Of Future Royalties [Line Items]
Liability for sale of future royalties at beginning of year	510,250	0
Net proceeds from sale of future royalties		490,950
Royalty revenue	(38,524)	0
Non-cash interest expense	43,200	19,300
Liability for sale of future royalties at end of year	$ 514,926	$ 510,250	$ 0

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Equity - Additional Information (Details) - USD ($) $ / shares in Units, $ in Millions	1 Months Ended		12 Months Ended		32 Months Ended
	Oct. 31, 2023	May 31, 2021	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2023
Stockholders Equity Line Items
Stock sold in at-the-market offering			1,175,584
Net proceeds from at-the-market offering			$ 53.3
Pre Funded Warrant
Stockholders Equity Line Items
Number of warrants exercised			0		0
Underwritten Public Offering
Stockholders Equity Line Items
Common stock shares sold	9,833,334
Shares purchased by underwriters	1,500,000
Public offering price	$ 30
Underwritten Public Offering | Pre Funded Warrant
Stockholders Equity Line Items
Net proceeds from sale of common stock	$ 326.5
Underwritten Public Offering Shares	1,666,722
Pre-funded warrant price	$ 29.999
Common stock warrants, exercise price	$ 0.001
Open Market Sale
Stockholders Equity Line Items
Common stock shares sold				0
Stock sold in at-the-market offering					2,225,956
Net proceeds from at-the-market offering					$ 132.2
Option to sell common stock aggregate offering price		$ 350.0

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Stock-Based Awards - Additional Information (Details) - USD ($) $ / shares in Units, $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Jun. 30, 2023	Feb. 01, 2021	Feb. 05, 2014
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Total intrinsic value of options exercised	$ 4.9	$ 2.6	$ 38.8
Cash received from exercise of options	$ 2.7	$ 6.2	$ 36.6
weighted-average estimated fair value	$ 25.53	$ 34.77	$ 70.84
Total estimated fair value of options vested	$ 59.7	$ 58.7	$ 48.1
Total unrecognized compensation cost	219.8
Weighted-average period to recognize cost		2 years 2 months 12 days
Stock-based compensation capitalized to inventory	1.9	$ 2.2	1.7
Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Total fair value of shares vested	54.6	47.1	35.5
Aggregate intrinsic value	33.0	37.8	69.9
Performance Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Total fair value of shares vested	3.9	1.6	9.2
Aggregate intrinsic value	1.3	$ 2.0	$ 18.9
Performance Stock Options [Member]
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
weighted-average estimated fair value		$ 28.76
Total estimated fair value of options vested	$ 3.4
Maximum | Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Stock based awards vesting period	4 years
Minimum | Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Stock based awards vesting period	1 year
2014 Incentive Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock authorized for future issuance						2,250,000
Automatic increases in shares available for grant effective date	Jan. 01, 2015
Shares available for grant, ending date	Jun. 07, 2023
2023 Incentive Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock authorized for future issuance				4,500,000
2023 Plan and Inducement Plan | Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Option vesting rights, percentage			25.00%
Stock based awards vesting period			4 years
2023 Plan and Inducement Plan | Maximum | Employee Stock Option
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Award expiration period			10 years
2023 Plan and Inducement Plan | First Anniversary | Employee Stock Option
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Option vesting rights, percentage			25.00%
2023 Plan and Inducement Plan | Shares Vesting Monthly After First Anniversary | Employee Stock Option
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Option vesting rights, percentage			2.08%
2014 Equity Incentive, 2023 Incentive and Employment Inducement Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock authorized for future issuance	19,610,125
2014 Employee Stock Purchase Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock authorized for future issuance	6,609,795
Percentage of statutory stock awards	85.00%
Common stock shares issued	195,462
Employment Inducement Plan | Maximum
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock available for grant					850,000

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Stock-Based Awards - Summary of Activity Under Stock Option Plans Including 2011 Plan and 2014 Plan and 2023 Plan (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Share-Based Payment Arrangement [Abstract]
Number of Options, Outstanding, Beginning Balance	7,773,367
Number of Options, Options granted	2,123,256
Number of Options, Options exercised	(209,793)
Number of Options, Options cancelled	(899,118)
Number of Options, Outstanding, Ending Balance	8,787,712	7,773,367
Vested and exercisable December 31, 2023	5,415,110
Vested and expected to vest December 31, 2023	8,461,973
Weighted Average Exercise Price, Outstanding, Beginning Balance	$ 72.56
Weighted Average Exercise Price, Options granted	45.05
Weighted Average Exercise Price, Options exercised	13.07
Weighted Average Exercise Price, Options cancelled	71.56
Weighted Average Exercise Price, Outstanding, Ending Balance	67.43	$ 72.56
Weighted- Average Exercise Price,Weighted Average Exercise Price	73.28
Weighted Average Exercise Price, Vested and expected to vest December 31, 2023	$ 67.96
Weighted Average Remaining Contractual Term (Years), Outstanding	6 years 4 months 20 days	6 years 7 months 6 days
Weighted Average Remaining Contractual Term (Years), Vested and exercisable - December 31, 2023	4 years 11 months 15 days
Weighted-Average Remaining Contractual Term,Vested and expected to vest December 31, 2023	6 years 3 months 14 days
Aggregate Intrinsic Value, Outstanding	$ 7,558	$ 8,476
Aggregate Intrinsic Value, Vested and exercisable - December 31, 2023	1,214
Aggregate Intrinsic Value, Vested and expected to vest - December 31, 2023	$ 6,794

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Stock-Based Awards- Summary Activity Under the Performance Stock Option (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Share-Based Compensation Arrangement by Share-Based Payment Award [Line Items]
Vested and exercisable December 31, 2023	5,415,110
Vested and expected to vest December 31, 2023	8,461,973
Weighted- Average Exercise Price,Weighted Average Exercise Price	$ 73.28
Weighted Average Exercise Price, Vested and expected to vest December 31, 2023	$ 67.96
Weighted-Average Remaining Contractual Term,Vested and expected to vest December 31, 2023	6 years 3 months 14 days
Weighted Average Remaining Contractual Term (Years), Vested and exercisable - December 31, 2023	4 years 11 months 15 days
Aggregate Intrinsic Value, Vested and exercisable - December 31, 2023	$ 1,214
Aggregate Intrinsic Value, Vested and expected to vest - December 31, 2023	$ 6,794
Performance Stock Options [Member]
Share-Based Compensation Arrangement by Share-Based Payment Award [Line Items]
Outstanding, Number of Shares, Unvested, Beginning Balance	1,624,599
PSOs cancelled	(243,601)
Outstanding, Number of Shares, Unvested, Ending Balance	1,380,998	1,624,599
Vested and exercisable December 31, 2023	117,865
Vested and expected to vest December 31, 2023	983,173
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Beginning Balance	$ 67.37
Weighted Average Exercise Price ,PSOs cancelled	67.37
Weighted- Average Exercise Price,Outstanding December 31, 2023	67.37	$ 67.37
Weighted- Average Exercise Price,Weighted Average Exercise Price	67.37
Weighted Average Exercise Price, Vested and expected to vest December 31, 2023	$ 67.37
Weighted-Average Remaining Contractual Term,Outstanding at December 31, 2023	3 years 1 month 24 days	4 years 1 month 20 days
Weighted-Average Remaining Contractual Term,Vested and expected to vest December 31, 2023	3 years 1 month 20 days
Weighted Average Remaining Contractual Term (Years), Vested and exercisable - December 31, 2023	3 years 1 month 2 days
Aggregate Intrinsic Value, Outstanding	$ 0	$ 0
Aggregate Intrinsic Value, Vested and exercisable - December 31, 2023	0
Aggregate Intrinsic Value, Vested and expected to vest - December 31, 2023	$ 0

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Stock-Based Awards - Summary of Activity Under Restricted Stock Units (RSUs) from 2014 Plan (Details) - Restricted Stock Units	12 Months Ended
	Dec. 31, 2023 $ / shares shares
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Outstanding, Number of Shares, Unvested, Beginning Balance | shares	2,129,153
Number of shares, granted | shares	2,447,170
Number of shares, vested | shares	(738,130)
Number of shares, cancelled | shares	(394,081)
Outstanding, Number of Shares, Unvested, Ending Balance | shares	3,444,112
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Beginning Balance | $ / shares	$ 75.11
Weighted-Average Grant Date Fair Value, granted | $ / shares	44.52
Weighted-Average Grant Date Fair Value, vested | $ / shares	73.99
Weighted-Average Grant Date Fair Value, cancelled | $ / shares	61.22
Weighted- Average Exercise Price,Outstanding December 31, 2023 | $ / shares	$ 55.21

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Stock-Based Awards - Summary of Activity Under PSUs from 2014 Plan (Details) - Performance Stock Units	12 Months Ended
	Dec. 31, 2023 $ / shares shares
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Outstanding, Number of Shares, Unvested, Beginning Balance | shares	209,230
Number of shares, granted | shares	362,470
Number of shares, vested | shares	(27,581)
Number of shares, cancelled | shares	(38,013)
Outstanding, Number of Shares, Unvested, Ending Balance | shares	506,106
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Beginning Balance | $ / shares	$ 98.09
Weighted-Average Grant Date Fair Value, granted | $ / shares	50.29
Weighted-Average Grant Date Fair Value, vested | $ / shares	141.86
Weighted-Average Grant Date Fair Value, cancelled | $ / shares	106.8
Weighted- Average Exercise Price,Outstanding December 31, 2023 | $ / shares	$ 60.82

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Stock-Based Awards - Summary of Stock-Based Compensation Recognized (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	$ 135,213	$ 130,368	$ 104,979
Cost of sales
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	1,166	902	871
Research and development
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	74,531	74,464	59,097
Selling, general and administrative
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	$ 59,516	$ 55,002	$ 45,011

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Stock-Based Awards - Fair Value of Stock Option Awards Granted Estimated Using Black-Scholes Option-Pricing Model (Details)	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Stock Options
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Expected term in years	6 years 25 days	6 years 25 days	6 years 21 days
Expected volatility	55.00%	56.00%	60.00%
Risk-free interest rate	4.20%	2.00%	1.00%
Expected dividend rate	0.00%	0.00%	0.00%
Granted [Member]
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Expected term in years		3 years 7 months 6 days
Expected volatility		57.00%
Risk-free interest rate		1.50%
Expected dividend rate		0.00%

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Defined Contribution Plan - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Defined Contribution Pension And Other Post Retirement Plan Disclosure [Abstract]
Contribution expenses	$ 9.7	$ 9.0	$ 5.5

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Income Taxes - Components of Company's Loss Before Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Income Tax Disclosure [Abstract]
Domestic	$ 608,166	$ 703,411	$ 455,314
Foreign	298	(1,686)	(2,333)
Total loss before income taxes	$ 608,464	$ 701,725	$ 452,981

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Income Taxes - Components of Company's Income Tax Provision (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Current provision for income taxes:
State	$ (3,187)	$ 6,062	$ (14)
International	3,127	1,274	1,058
Total current tax provision	(60)	7,336	1,044
Deferred tax provision:
State	(1,608)	(1,640)
International	(157)
Total deferred tax provision	(1,765)	(1,640)
Total (benefit from) provision for income taxes	$ (1,825)	$ 5,696	$ 1,044

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Income Taxes - Additional Information (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2012	Dec. 31, 2011
Tax Credit Carryforward [Line Items]
Current state income tax expense	$ (60)	$ 7,336	$ 1,044
Deferred tax assets net operating loss, federal tax credits				$ 200	$ 200
Deferred tax assets net operating loss carryforwards	266,253	231,835
Valuation allowance increased	141,300	193,800
Effective income tax rate unrecognized tax benefits	1,300
Deferred tax liability increase (decrease), net	(1,600)
Deferred income tax expense	1,608	1,640
Recognized accrued interest and penalties	200	0	$ 0
Undistributed earnings of foreign subsidiaries	10,800
Federal
Tax Credit Carryforward [Line Items]
Deferred tax assets operating loss carryforwards subject to expiration	$ 1,004,800	756,600
Operating loss carryforwards expiration year	2031
Tax credit carryforwards	$ 46,900	32,600
Tax credit carryforwards expiration year	2030
Deferred tax assets net operating loss carryforwards				3,600	3,600
Federal | Orphan Drug Credits [Member]
Tax Credit Carryforward [Line Items]
Deferred tax assets operating loss carryforwards subject to expiration	$ 269,600	239,300
Operating loss carryforwards expiration year	2031
State
Tax Credit Carryforward [Line Items]
Current state income tax expense	$ 4,800	6,100
Deferred tax assets operating loss carryforwards subject to expiration	$ 659,900	710,000
Operating loss carryforwards expiration year	2031
Tax credit carryforwards	$ 74,400	$ 59,900
Deferred tax assets net operating loss carryforwards				$ 3,600	$ 3,600
International
Tax Credit Carryforward [Line Items]
Current state income tax expense	$ 3,000

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Income Taxes - Effective Tax Rate of Provision for Income Taxes from Federal Statutory Rate (Details)	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Effective Income Tax Rate Reconciliation, Percent [Abstract]
Federal statutory income tax rate	21.00%	21.00%	21.00%
State income taxes, net of federal benefit	0.80%	(0.40%)
Federal tax credits	7.30%	5.90%	7.20%
Other	(0.70%)	(0.10%)	0.50%
Nondeductible permanent items	(0.30%)	(0.60%)	(0.80%)
Stock-based compensation	(1.80%)	(1.20%)	1.30%
Uncertain tax positions	(1.40%)	(1.20%)	(1.40%)
Change in valuation allowance	(24.10%)	(24.00%)	(27.90%)
Foreign rate differential	(0.50%)	(0.20%)	(0.10%)
Provision for income taxes	0.30%	(0.80%)	(0.20%)

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Income Taxes - Schedule of Tax Effect of Temporary Differences to Significant Portions of Deferred Tax Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Deferred tax assets:
Loss carryforwards	$ 266,253	$ 231,835
Tax credits	305,198	260,546
Stock options	44,795	39,784
Accruals and reserves	27,694	27,029
Fixed assets and intangibles	33,853	39,233
Liabilities for sales of future royalties	205,400	214,900
Basis difference in equity investments	8,423	8,971
Capitalized research and development costs	149,898	75,335
Other	281	3,028
Gross deferred tax assets	1,041,795	900,661
Valuation allowance	(1,035,836)	(894,518)
Total deferred tax assets	5,959	6,143
Deferred tax liabilities:
Gross deferred tax liabilities	(36,017)	(37,810)
Net deferred tax liabilities	(30,058)	(31,667)
Right-of-use Lease Assets
Deferred tax liabilities:
Gross deferred tax liabilities	(5,329)	(6,143)
In-process Research and Development [Member]
Deferred tax liabilities:
Gross deferred tax liabilities	$ (30,688)	$ (31,667)

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Income Taxes - Unrecognized Tax Benefits (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Income Tax Disclosure [Abstract]
Balance at beginning of year	$ 66,794	$ 55,360	$ 46,662
Additions based on tax positions related to current year	12,562	11,316	8,542
Additions for tax positions of prior years	642	377	356
Reductions for tax positions of prior years	0	(259)	(200)
Balance at end of year	$ 79,998	$ 66,794	$ 55,360

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Commitments and Contingencies - Additional Information (Details)	12 Months Ended
	Dec. 31, 2023
Manufacturing and Services
Commitments And Contingencies Disclosure Line Items
Contractual Obligation Maturity Period	12 months

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Commitments and Contingencies - Summary of Aggregate Payments under Contractually Binding Manufacturing and Service Agreements (Details) - Manufacturing and Services $ in Thousands	Dec. 31, 2023 USD ($)
Commitments And Contingencies Disclosure Line Items
2024	$ 27,899
2025	5,718
Contractual Obligation, Total	$ 33,617

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Related Party Transaction - Additional Information (Details) - USD ($) $ in Thousands	1 Months Ended	12 Months Ended
	Jul. 31, 2022	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Related Party Transaction Line Items
Contribution amount paid	$ 1,000
Contribution period	4 years
Research and development		$ 648,449	$ 705,789	$ 497,153
Non Profit Foundation
Related Party Transaction Line Items
Research and development		$ 300	$ 300

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Net Loss per Share - Computation of Basic and Diluted Net Loss per Share (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Numerator:
Net loss	$ (606,639)	$ (707,421)	$ (454,025)
Denominator:
Weighted-average shares used to computing net loss per share, basic	73,543,862	69,914,225	67,795,540
Weighted-average shares used to computing net loss per share, diluted	73,543,862	69,914,225	67,795,540
Net loss per share, basic	$ (8.25)	$ (10.12)	$ (6.7)
Net loss per share, diluted	$ (8.25)	$ (10.12)	$ (6.7)

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Net Loss per Share - Outstanding Shares of Common Stock Equivalents Excluded from Computation of Diluted Net Loss per Share (Details) - shares	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common stock equivalents excluded from computation of diluted net loss per share	14,160,736	11,298,516	8,217,574
Options to Purchase Common Stock, RSUs, and PSUs
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common stock equivalents excluded from computation of diluted net loss per share	14,152,286	11,290,935	8,214,063
Employee Stock Purchase Plan
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common stock equivalents excluded from computation of diluted net loss per share	8,450	7,581	3,511

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Accumulated Other Comprehensive Income (Loss) - Schedule of Total Accumulated Other Comprehensive Income (Loss) (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Accumulated Other Comprehensive Income (Loss), Net of Tax [Abstract]
Cumulative foreign currency translation adjustment	$ (606)	$ (845)
Unrealized gain (loss) on securities available-for-sale	1,253	(5,728)
Total accumulated other comprehensive income (loss)	$ 647	$ (6,573)