UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 20549

FORM 10-Q

(Mark One)

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

For the quarterly period ended March 31, 2025

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 Number: 001-42382

Septerna, Inc.

(Exact Name of Registrant as Specified in its Charter)

Delaware	84-3891440
(State or other jurisdiction of incorporation or organization)	(I.R.S. Employer Identification No.)
250 East Grand Avenue South San Francisco, CA	94080
(Address of principal executive offices)	(Zip Code)

Registrant’s telephone number, including area code: (650) 338-3533

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

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

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 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, 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 is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒

As of May 7, 2025, the registrant had 44,558,338 shares of common stock, $0.001 par value per share, outstanding.

1

TABLE OF CONTENTS

		Page
PART I.	FINANCIAL INFORMATION	1
Item 1.	Financial Statements (unaudited)	1
	Condensed Balance Sheets	1
	Condensed Statements of Operations and Comprehensive Loss	2
	Condensed Statements of Convertible Preferred Stock and Stockholders’ Equity (Deficit)	3
	Condensed Statements of Cash Flows	4
	Notes to Condensed Financial Statements (unaudited)	5
Item 2.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	16
Item 3.	Quantitative and Qualitative Disclosures About Market Risk	26
Item 4.	Controls and Procedures	26
PART II.	OTHER INFORMATION	27
Item 1.	Legal Proceedings	27
Item 1A.	Risk Factors	27
Item 2.	Unregistered Sales of Equity Securities and Use of Proceeds	28
Item 3.	Defaults Upon Senior Securities	29
Item 4.	Mine Safety Disclosures	29
Item 5.	Other Information	29
Item 6.	Exhibits	30
Signatures		31

We own various U.S. federal trademark applications and unregistered trademarks, including our company name and logo, that we use in connection with the operation of our business. This Quarterly Report on Form 10-Q (this “Quarterly Report”) includes our trademarks and trade names which are protected under applicable intellectual property laws and are our property. This Quarterly Report also contains trademarks, trade names and service marks of other companies, which are the property of their respective owners. Solely for convenience, trademarks, trade names and service marks referred to in this Quarterly Report may appear without the ®, ™ or SM symbols, but such references are not intended to indicate, in any way, that we will not assert, to the fullest extent permitted under applicable law, our rights or the right of the applicable licensor to these trademarks, trade names and service marks. We do not intend our use or display of other parties’ trademarks, trade names or service marks to imply, and such use or display should not be construed to imply, a relationship with, or endorsement or sponsorship of us by, these other parties.

From time to time, we may use our website as well as social media, including our X (formerly known as Twitter) account at Septerna_Inc and our LinkedIn account at https://www.linkedin.com/company/septernainc/ to distribute material information about us and for complying with our disclosure obligations under Regulation FD. Our financial and other material information is routinely posted to and accessible on the Investors section of our website, available at www.Septerna.com. Investors are encouraged to review the Investors section of our website because we may post material information on that site that is not otherwise disseminated by us. Information that is contained in and can be accessed through our website or our social media are not incorporated into, and does not form a part of, this Quarterly Report.

i

SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

This Quarterly Report contains express or implied forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements are based on our management’s belief and assumptions and on information currently available to our management. Although we believe that the expectations reflected in these forward-looking statements are reasonable, these statements relate to future events or our future operational or 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. Forward-looking statements in this Quarterly Report include, but are not limited to, statements about:

•the initiation, timing, progress, results and costs of conducting our research and development programs and our current and future preclinical studies and anticipated clinical trials, including statements regarding the timing of initiation and completion of studies or trials and related preparatory work, the period during which the results of the trials will become available, and our current and future programs;

•our ability to demonstrate, and the timing of, preclinical proof-of-concept in vivo and ex vivo for multiple programs;

•our ability to advance any product candidates that we may identify and successfully complete any clinical studies, including the manufacture of any such product candidates;

•the timing, scope and likelihood of regulatory filings and approvals, including timing of Investigational New Drug (“IND”) applications or comparable foreign applications, and final U.S. Food and Drug Administration (the “FDA”) approval of our product candidates;

•the timing, scope or likelihood of foreign regulatory filings and approvals;

•the implementation of our business model, and strategic plans for our business, product candidates, and technology;

•the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates and other product candidates we may develop, including the extensions of existing patent terms where available, the validity of intellectual property rights held by third parties, and our ability not to infringe, misappropriate or otherwise violate any third-party intellectual property rights;

•developments relating to our competitors and our industry;

•our ability to leverage programs within our initial target indications and to progress additional programs to further develop our pipeline;

•our ability of our preclinical studies and clinical trials to demonstrate safety and efficacy of our product candidates, and other positive results;

•the partnership with Novo Nordisk A/S (“Novo”) and the intended and potential benefits thereof, including the receipt of expected upfront payment upon the effectiveness of the collaboration agreement, as well as potential milestone and royalty payments from commercial product sales, along with tiered royalties based on global net sales, if any;

•Novo's ability to develop and commercialize potential oral small molecule therapies for metabolic-related diseases and the potential of G protein-coupled receptors, including the GLP-1, GIP, and glucagon receptors, to address the unmet medical need for treating obesity, type 2 diabetes and other related conditions;

•our ability to maintain existing collaborations and strategic partnerships, to identify and enter into future license agreements and collaborations, and to realize the intended and potential benefits of such agreements and collaborations;

•our ability to rely on third-party manufacturers and successfully manufacture product candidates for preclinical use, clinical trials and on a larger scale for commercial use, if approved;

•our ability to realize the benefits of collaborations for the development and commercialization of our product candidates;

•our ability to commercialize any of our product candidates;

•developments related to our proprietary Native Complex Platform™;

•regulatory developments in the United States and foreign countries;

•our ability to obtain funding for our operations necessary to complete further development and commercialization of our product candidates;

•the size and growth potential of the markets for our product candidates and our ability to serve those markets;

ii

•our need for and ability to attract and retain key scientific, management and other personnel and to identify, hire, and retain additional qualified professionals;

•our expectations regarding the period during which we will remain an emerging growth company under the Jumpstart Our Business Startups Act of 2012 (“JOBS Act”);

•the period over which we expect our existing cash, cash equivalents and investments will be sufficient to fund our operating expenses and capital expenditure requirements;

•our anticipated use of our existing resources;

•our financial performance and estimates of our future expenses, capital requirements, and our needs for additional financing;

•the impact of macroeconomic and geopolitical developments on our business, including rising inflation and capital market disruptions, changes in U.S. governmental agencies, new or increased international tariffs and retaliatory tariffs, trade protection measures, economic sanctions and economic slowdowns or recessions that may result from such developments which could harm our research and development efforts as well as the value of our common stock and our ability to access capital markets; and

•other risks and uncertainties, including those listed under the section titled “Risk Factors” in Part II, Item 1A.

In some cases, you can identify forward-looking statements by terminology such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target,” “contemplate,” “possible,” “can,” or the negative of these terms or other comparable terminology, and similar expressions, although not all forward-looking statements contain these identifying words. These statements are only predictions. You should not place undue reliance on forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, which are, in some cases, beyond our control and which could materially affect results. Factors that may cause actual results to differ materially from current expectations include, among other things, those listed under the section titled “Risk Factors” and elsewhere in this Quarterly Report. If one or more of these risks or uncertainties occur, or if our underlying assumptions prove to be incorrect, actual events or results may vary significantly from those implied or projected by the forward-looking statements. No forward-looking statement is a guarantee of future performance. You should read this Quarterly Report and the documents that we reference in this Quarterly Report and have filed with the Securities and Exchange Commission (the “SEC”) thereto completely and with the understanding that our actual future results may be materially different from any future results expressed or implied by these forward-looking statements.

The forward-looking statements in this Quarterly Report represent our views as of the date of this Quarterly Report. We do not undertake any obligation to publicly update any forward-looking statement except to the extent required by applicable law. You should therefore not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this Quarterly Report.

This Quarterly Report also contains estimates, projections and other information concerning our industry, our business and the markets for our product candidates. 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 that are assumed in this information. Unless otherwise expressly stated, we obtained this industry, business, market, and other data from our own internal estimates and research as well as 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. All of the market data used in this Quarterly Report involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data. Industry publications and third-party research, surveys, and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of such information. Our estimates of the potential market opportunities for our product candidates include several key assumptions based on our industry knowledge, industry publications, third-party research, and other surveys, which may be based on a small sample size and may fail to accurately reflect market opportunities. While we believe that our internal assumptions are reasonable, no independent source has verified such assumptions.

This Quarterly Report contains summaries of certain provisions contained in some of the documents described herein, but reference is made to the actual documents for complete information. All of the summaries are qualified in their entirety by the actual documents. Copies of some of the documents referred to herein have been filed as exhibits to this Quarterly Report. Unless the context otherwise requires, reference in this Quarterly Report to the terms “Septerna,” “the Company,” “we,” “us,” “our,” and similar designations refer to Septerna, Inc.

iii

PART I—FINANCIAL INFORMATION

Item 1. Condensed Financial Statements.

SEPTERNA, INC.

Condensed Balance Sheets

(In thousands, except for share and per share data)

(Unaudited)

	March 31,			December 31,
	2025			2024
Assets
Current assets:
Cash and cash equivalents	$	210,045		$	238,196
Marketable securities		125,960			112,727
Accounts receivable		250			171
Prepaid expenses and other current assets		6,214			5,730
Total current assets		342,469			356,824
Marketable securities, non-current		62,242			69,866
Property and equipment, net		5,042			5,090
Operating lease right-of-use assets		23,085			23,602
Restricted cash		905			905
Other non-current assets		277			267
Total assets	$	434,020		$	456,554
Liabilities and Stockholders' Equity
Current liabilities:
Accounts payable	$	4,349		$	3,200
Accrued expenses and other current liabilities		4,352			7,798
Operating lease liabilities, current		1,937			1,851
Total current liabilities		10,638			12,849
Operating lease liabilities, non-current		23,089			23,625
Other non-current liabilities		27			33
Total liabilities		33,754			36,507
Commitments and contingencies (Note 5)
Stockholders' equity:
Preferred stock, $0.001 par value per share; 10,000,000 shares authorized as of    March 31, 2025 and December 31, 2024; no shares issued and outstanding as    of March 31, 2025 and December 31, 2024		—			—
Common stock, $0.001 par value per share, 500,000,000 shares    authorized at March 31, 2025 and December 31, 2024; 44,448,435 and    44,422,505 shares issued and outstanding at March 31, 2025 and December 31, 2024,    respectively; 457,099 and 576,829 shares subject to repurchase as of    March 31, 2025 and December 31, 2024, respectively		44			44
Additional paid-in capital		539,874			538,321
Accumulated other comprehensive income		198			56
Accumulated deficit		(139,850	)		(118,374	)
Total stockholders' equity		400,266			420,047
Total liabilities and stockholders' equity	$	434,020		$	456,554

The accompanying notes are an integral part of these condensed financial statements.

1

SEPTERNA, INC.

Condensed Statements of Operations and Comprehensive Loss

(In thousands, except for share and per share data)

(Unaudited)

	Three Months Ended March 31,
	2025			2024
Revenue	$	219		$	317
Operating expenses:
Research and development		19,271			13,153
General and administrative		6,858			2,654
Total operating expenses		26,129			15,807
Loss from operations		(25,910	)		(15,490	)
Other income, net:
Interest income		4,462			1,279
Other expense, net		(28	)		(48	)
Total other income, net		4,434			1,231
Loss before benefit for income taxes		(21,476	)		(14,259	)
Benefit for income taxes		—			93
Net loss attributable to common stockholders	$	(21,476	)	$	(14,166	)
Net loss per share attributable to common stockholders, basic and diluted	$	(0.49	)	$	(6.35	)
Weighted-average shares outstanding, basic and diluted		43,937,410			2,232,246
Comprehensive loss:
Net loss	$	(21,476	)	$	(14,166	)
Net unrealized gain (loss) on marketable securities		142			(7	)
Total other comprehensive income (loss)		142			(7	)
Comprehensive loss	$	(21,334	)	$	(14,173	)

The accompanying notes are an integral part of these condensed financial statements.

2

SEPTERNA, INC.

Condensed Statements of Convertible Preferred Stock and Stockholders’ Equity (Deficit)

(In thousands, except for share data)

(Unaudited)

					Additional		Accumulated Other					Total
	Common Stock				Paid-In		Comprehensive		Accumulated			Stockholders'
	Shares		Amount		Capital		Income		Deficit			Equity
Balance at December 31, 2024		44,422,505	$	44	$	538,321	$	56	$	(118,374	)	$	420,047
Issuance of common stock    upon exercise of stock options		25,930		—		66		—		—			66
Vesting of restricted common    stock		—		—		5		—		—			5
Stock-based compensation    expense		—		—		1,482		—		—			1,482
Net unrealized gain on    marketable securities		—		—		—		142		—			142
Net loss		—		—		—		—		(21,476	)		(21,476	)
Balance at March 31, 2025		44,448,435	$	44	$	539,874	$	198	$	(139,850	)	$	400,266

	Convertible Preferred Stock													Additional		Accumulated Other						Total
	Series A				Series B				Common Stock					Paid-In		Comprehensive			Accumulated			Stockholders'
	Shares		Amount		Shares		Amount		Shares			Amount		Capital		Loss			Deficit			Deficit
Balance at December 31, 2023		75,000,000	$	74,694		60,828,720	$	74,521		3,168,134		$	3	$	8,199	$	—		$	(46,576	)	$	(38,374	)
Issuance of common stock    upon exercise of stock options		—		—		—		—		217			—		1		—			—			1
Vesting of restricted common    stock		—		—		—		—		—			—		6		—			—			6
Repurchase of unvested    restricted common stock		—		—		—		—		(11,517	)		—		—		—			—			—
Stock-based compensation    expense		—		—		—		—		—			—		577		—			—			577
Net unrealized loss on    marketable securities		—		—		—		—		—			—		—		(7	)		—			(7	)
Net loss		—		—		—		—		—			—		—		—			(14,166	)		(14,166	)
Balance at March 31, 2024		75,000,000	$	74,694		60,828,720	$	74,521		3,156,834		$	3	$	8,783	$	(7	)	$	(60,742	)	$	(51,963	)

The accompanying notes are an integral part of these condensed financial statements.

3

SEPTERNA, INC.

Condensed Statements of Cash Flows

(In thousands)

(Unaudited)

	Three Months Ended March 31,
	2025			2024
Cash flows from operating activities:
Net loss	$	(21,476	)	$	(14,166	)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization		397			316
Non-cash operating lease expense		516			243
Stock-based compensation		1,482			577
Accretion of premiums (discounts), net		(965	)		(72	)
Deferred income tax		—			(93	)
Other		(11	)		13
Changes in operating assets and liabilities:
Prepaid expenses and other current assets		(488	)		(1,361	)
Accounts receivable		(79	)		(240	)
Other non-current assets		(9	)		(24	)
Accounts payable		1,186			(143	)
Accrued expenses and other current liabilities		(3,446	)		(1,617	)
Operating lease, net		(450	)		(144	)
Net cash used in operating activities		(23,343	)		(16,711	)
Cash flows from investing activities:
Purchases of property and equipment		(382	)		(764	)
Proceeds from sale of non-financial asset		—			22,625
Purchases of marketable securities		(49,715	)		(12,293	)
Maturities of marketable securities		45,223			—
Net cash (used in) provided by investing activities		(4,874	)		9,568
Cash flows from financing activities:
Repurchases of unvested restricted common stock		—			(1	)
Proceeds from exercise of stock options		66			1
Net cash provided by financing activities		66			—
Net decrease in cash, cash equivalents and restricted cash		(28,151	)		(7,143	)
Cash, cash equivalents and restricted cash, beginning of period		239,101			89,388
Cash, cash equivalents and restricted cash, end of period	$	210,950		$	82,245

Cash, Cash Equivalents and Restricted Cash:

	As of March 31,
	2025		2024
Cash and cash equivalents	$	210,045	$	81,340
Restricted cash		905		905
Total cash, cash equivalents and restricted cash at end of period	$	210,950	$	82,245

The accompanying notes are an integral part of these condensed financial statements.

4

SEPTERNA, INC.

Notes to UNAUDITED Condensed Financial Statements

Note 1. Organization and Basis of Presentation

Description of the Business

Septerna, Inc. (“Septerna” or the “Company”) is a biotechnology company pioneering a new era of G protein-coupled receptor (“GPCR”) oral small molecule drug discovery powered by its proprietary Native Complex Platform™. The Company’s industrial-scale platform aims to unlock the full potential of GPCR therapies and has led to the discovery and development of its deep pipeline of product candidates focused on treating patients in three therapeutic areas: endocrinology, immunology and inflammation, and metabolic diseases.

The Company’s proprietary Native Complex Platform™ replicates the natural structure, function, and dynamics of GPCRs outside of cells at an industrial scale. The Company’s foundational technologies enable it to isolate, purify, and reconstitute full-length, properly folded GPCR proteins within ternary complexes with ligands and transducer proteins in a lipid bilayer that mimics the cell membrane. The Company then applies state-of-the-art discovery tools and technologies to these defined and tunable protein complexes to structurally design, screen for, and optimize potential product candidates. Leveraging its platform, the Company has transformed GPCR oral small molecule drug discovery to an industrialized and iterative structure-based drug design approach to expand the landscape of druggable GPCR targets with novel oral small molecule medicines for patients. The Company’s Native Complex Platform™ is designed to enable it to target certain GPCRs for the first time, uncover novel binding pockets for validated receptors, and pursue a wide spectrum of pharmacologies, including agonists, antagonists, and allosteric modulators, to affect GPCR signaling in different ways to achieve desired therapeutic effects.

The Company was incorporated in Delaware in December 2019, under the name GPCR NewCo, Inc. In June 2021, the Company changed its name to Septerna, Inc. The Company is headquartered in South San Francisco, California.

Reverse Stock Split

On October 18, 2024, the Company effected a 1-for-8.6103 reverse stock split of its issued and outstanding shares of common stock. Upon the effectiveness of the reverse stock split, (i) all shares of outstanding common stock were adjusted; (ii) the conversion ratio of the convertible preferred stock was adjusted; (iii) the number of shares of common stock for which each outstanding option to purchase common stock is exercisable were adjusted; and (iv) the exercise price of each outstanding option to purchase common stock was adjusted. All of the outstanding common stock (including shares of common stock subject to the Company’s options and as converted for the outstanding convertible preferred stock), share prices, exercise prices and per share amounts contained in the condensed financial statements have been retroactively adjusted to reflect this reverse stock split for all periods presented. The par value per share and the authorized number of shares of common stock and preferred stock were not adjusted as a result of the reverse stock split. The number of authorized shares did not change.

Initial Public Offering

In October 2024, the Company completed its initial public offering (“IPO”), pursuant to which it issued and sold an aggregate of 18.4 million shares of its common stock at the IPO price of $18.00 per share, including 2.4 million shares that were issued to the underwriters pursuant to the full exercise of their option to purchase additional shares, resulting in net proceeds of $302.8 million, net of total offering costs of $28.4 million. Immediately prior to the closing of the IPO, the Company’s then outstanding convertible preferred stock automatically converted into 22,839,774 shares of common stock.

Following the closing of the IPO, no shares of convertible preferred stock were authorized or outstanding. In connection with the completion of the IPO, on October 28, 2024, the Company’s certificate of incorporation was amended and restated to (i) authorize 500.0 million shares of common stock, par value $0.001 per share, which eliminates all references to the previously existing series of convertible preferred stock; and (ii) authorize 10.0 million shares of undesignated preferred stock, par value $0.001 per share, that may be issued from time to time by the Company’s board of directors in one or more series.

Liquidity and Capital Resources

The accompanying unaudited condensed financial statements have been prepared assuming the Company will continue as a going concern, which assumes that the Company will realize its assets and satisfies its liabilities in the normal course of business. The Company is subject to risks inherent in operating an early-stage biotechnology business. These risks include, but are not limited to, dependence on the development of marketable products, the ability to attract, retain, and motivate qualified personnel, rapid technological changes and the rapidly evolving nature of the biotechnology industry.

5

SEPTERNA, INC.

Notes to UNAUDITED Condensed Financial Statements (CONTINUED)

The Company has incurred significant losses and negative cash flows from operations since its inception and expects to incur losses as a result of its continued research and development activities. To date, none of the Company’s product candidates have been approved by the U.S. Food and Drug Administration (the “FDA”) for commercial sale and, therefore, the Company has not generated any revenue from product sales.

The Company historically financed its operations primarily through the issuance of convertible promissory notes, convertible preferred stock, and most recently, through the sale of its common stock in an IPO. The Company will need additional financing to support its continuing operations and pursue its growth strategy. Until such time as the Company can generate significant revenue from product sales, if ever, it expects to finance its operations through equity offerings, debt financings or other capital sources, including collaborations with other companies or other strategic transactions. The Company may not be able to obtain funding on acceptable terms, or at all. The terms of any financing may adversely affect the holdings or the rights of the Company’s stockholders.

For the three months ended March 31, 2025 and 2024, the Company incurred net losses of $21.5 million and $14.2 million, respectively. The Company had an accumulated deficit of $139.9 million as of March 31, 2025. The Company believes its cash, cash equivalents, and marketable securities of $398.2 million as of March 31, 2025 will be sufficient to fund its operations for, at least, 12 months from the date of issuance of the unaudited condensed financial statements.

Basis of Presentation

The accompanying unaudited interim condensed financial statements have been prepared in conformity with generally accepted accounting principles in the United States of America (“U.S. GAAP”) for interim financial information. Accordingly, they do not include all of the information and footnotes required by U.S. GAAP for complete financial statements. In the opinion of management, all adjustments (consisting only of normal recurring adjustments) that are necessary for the fair presentation of the unaudited interim condensed financial statements for the periods presented have been included. Any reference in these notes to applicable guidance is meant to refer to the authoritative GAAP as found in the Accounting Standards Codification and Accounting Standards Updates (“ASUs”), of the Financial Accounting Standards Board (“FASB”). The interim condensed financial statements are unaudited. The operating results presented in these unaudited interim condensed financial statements are not necessarily indicative of the results that may be expected for the full year or for any other future annual or interim period. Actual results could differ materially from estimates and assumptions. As appropriate, the Company assesses estimates each period and updates them to reflect current information, and generally reflect any changes in estimates in the period first identified.

The balance sheet data at December 31, 2024 was derived from the audited financial statements included in Septerna’s Annual Report on Form 10-K for the year ended December 31, 2024 as filed with the SEC on March 27, 2025. These interim unaudited condensed financial statements should be read in conjunction with the audited financial statements and related notes thereto included in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024.

Significant Accounting Policies

During the three months ended March 31, 2025, there were no changes to the Company’s significant accounting policies as described in Note 2 of the audited financial statements for the year ended December 31, 2024.

Recently Adopted Accounting Pronouncements

In November 2023, the FASB issued ASU 2023-07, Segment Reporting (Topic 280): Improvements to Reportable Segment Disclosures. ASU 2023-07 will improve reportable segment disclosure requirements, primarily through enhanced disclosures about significant segment expenses on an interim and annual basis. The ASU is effective for fiscal years beginning after December 15, 2023, and interim periods after December 5, 2024, with early adoption permitted. The Company adopted Topic 280 for its annual reporting for the year ended December 31, 2024 and for its interim reporting starting with the quarter ended March 31, 2025.

Accounting Pronouncements Not Yet Adopted

From time to time, new accounting pronouncements are issued by the FASB, under its Accounting Standards Codification (“ASC”) or other standard setting bodies, and adopted by the Company as of the specified date.

In November 2024, the FASB issued ASU No. 2024-03, Income Statement—Reporting Comprehensive Income—Expense Disaggregation Disclosures (Subtopic 220-40): Disaggregation of Income Statement Expenses, an accounting standard update that requires the Company to disclose more detailed information about the types of expenses (including employee compensation, depreciation, and amortization) included in each relevant income statement expense caption. The ASU is effective for fiscal years

6

SEPTERNA, INC.

Notes to UNAUDITED Condensed Financial Statements (CONTINUED)

beginning after December 15, 2026, and interim reporting periods beginning after December 15, 2027. Early adoption is permitted. The Company is currently evaluating the impact that this update will have on its disclosures.

In December 2023, the FASB issued ASU No. 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures, which enhances the transparency and decision usefulness of income tax disclosures. The standard is intended to improve income tax disclosures primarily related to the rate reconciliation and income taxes paid information. This update also includes certain other amendments to improve the effectiveness of income tax disclosures. The ASU is effective for fiscal years beginning after December 15, 2024, on a prospective basis. Early adoption and retrospective reporting are permitted. The Company is currently evaluating the impact of ASU 2023-09 on its interim condensed financial statements.

Note 2. Balance Sheet Components

Restricted Cash

Restricted cash is comprised of cash that is restricted as to withdrawal or use under the terms of certain contractual agreements. In connection with the Company’s lease agreement, the Company is required to maintain a collateral account to secure a letter of credit issued to its landlord. The collateral account is classified as restricted cash on the Company’s condensed balance sheets.

Prepaid Expenses and Other Current Assets

Prepaid expenses and other current assets consist of the following (in thousands):

	As of March 31,		As of December 31,
	2025		2024
Prepaid expenses	$	4,371	$	3,114
Interest receivable		1,076		953
Prepaid clinical trial costs		397		1,164
Prepaid bonus		279		260
Prepaid taxes		39		39
Other current assets		52		200
Prepaid expenses and other current assets	$	6,214	$	5,730

Property and Equipment, Net

Property and equipment, net consist of the following (in thousands):

	As of March 31,			As of December 31,
	2025			2024
Lab equipment	$	6,028		$	5,679
Furniture, fixtures, and office equipment		1,222			1,222
Leasehold improvements		717			717
Computer equipment		401			401
Total property and equipment		8,368			8,019
Less: Accumulated depreciation and amortization		(3,326	)		(2,929	)
Property and equipment, net	$	5,042		$	5,090

Depreciation and amortization expense was $0.4 million and $0.3 million for the three months ended March 31, 2025 and 2024, respectively.

7

SEPTERNA, INC.

Notes to UNAUDITED Condensed Financial Statements (CONTINUED)

Accrued Expenses and Other Current Liabilities

Accrued expenses and other current liabilities consist of the following (in thousands):

	As of March 31,		As of December 31,
	2025		2024
Accrued research and development expense	$	2,287	$	2,888
Accrued general and administrative expense		1,122		703
Accrued employee compensation expense		869		4,129
Other current liabilities		74		78
Accrued expenses and other current liabilities	$	4,352	$	7,798

Note 3. Revenue

The Company recognizes service revenue associated with the Vertex Research Service Agreement (the “Vertex Research Service Agreement”) over the performance period of the research services as the services are provided in accordance with ASC Topic 606, Revenue from Contracts with Customers (“ASC Topic 606”).

During the three months ended March 31, 2025 and 2024, the Company recorded service revenue of $0.2 million and $0.3 million related to research activities performed in connection with the Vertex Research Service Agreement, respectively.

As of March 31, 2025 and December 31, 2024, the Company’s accounts receivable was entirely attributed to Vertex Pharmaceuticals Incorporated (“Vertex”). As of March 31, 2025 and December 31, 2024, no allowance for credit loss was recorded related to accounts receivable.

Note 4. Marketable Securities and Fair Value Measurements

The Company records marketable securities and cash equivalents at their estimated fair values, which are based on market prices from a variety of industry standard data providers and generally represent quoted prices for similar assets in active markets or have been derived from observable market data.

Fair value is determined based on a three-tier hierarchy under the authoritative guidance for fair value measurements and disclosures that prioritizes the inputs used in measuring fair value as follows:

Level 1: Unadjusted quoted prices in active markets that are accessible at the measurement date for identical, unrestricted assets or liabilities;

Level 2: Quoted prices in markets that are not active or inputs which are observable, either directly or indirectly, for substantially the full term of the asset or liability; and

Level 3: Prices or valuation techniques that require inputs that are both significant to the fair value measurements and unobservable (i.e., supported by little or no market activity).

Money market funds are highly liquid investments and are classified as Level 1. The pricing information for these assets is readily available and can be independently validated as of the measurement date. Marketable securities, including U.S. Treasury securities, U.S. government agency securities, commercial paper, and corporate debt securities, are classified as Level 2. These securities are valued using fair value from third-party pricing services, which may use observable inputs based on real-time trade data for similar assets, broker/dealer quotes, bids and/or offers and other observable inputs.

The carrying amounts of the Company’s prepaid and other current assets, accounts payable, and accrued and other current liabilities approximate fair value due to their short maturities.

8

SEPTERNA, INC.

Notes to UNAUDITED Condensed Financial Statements (CONTINUED)

The fair value measurements of the Company’s cash equivalents and marketable securities are identified at the following levels within the fair value hierarchy (in thousands):

	March 31, 2025
			Fair Value Measurement
	Total		Level 1		Level 2		Level 3
Cash equivalents:
Money market funds	$	119,190	$	119,190	$	—	$	—
Commercial paper		87,295		—		87,295		—
Corporate debt securities		705		—		705		—
Marketable securities, current:
U.S. treasury securities		81,541		—		81,541		—
Commercial paper		26,709		—		26,709		—
U.S. government agency    securities		16,234		—		16,234		—
Corporate debt securities		1,476		—		1,476		—
Marketable securities, non-current:
U.S. treasury securities		59,242		—		59,242		—
U.S. government agency    securities		2,517		—		2,517		—
Corporate debt securities		483		—		483		—
Total measured at fair value	$	395,392	$	119,190	$	276,202	$	—

	As of December 31, 2024
			Fair Value Measurement
	Total		Level 1		Level 2		Level 3
Cash equivalents:
Money market funds	$	141,779	$	141,779	$	—	$	—
U.S. government agency    securities		8,059		—		8,059		—
Commercial paper		82,527		—		82,527		—
Marketable securities, current:
U.S. treasury securities		73,555		—		73,555		—
Commercial paper		23,487		—		23,487		—
U.S. government agency    securities		14,193		—		14,193		—
Corporate debt securities		1,492		—		1,492		—
Marketable securities, non-current:
U.S. treasury securities		65,406		—		65,406		—
U.S. government agency    securities		2,514		—		2,514		—
Corporate debt securities		1,946		—		1,946		—
Total measured at fair value	$	414,958	$	141,779	$	273,179	$	—

9

SEPTERNA, INC.

Notes to UNAUDITED Condensed Financial Statements (CONTINUED)

Marketable Securities

As of March 31, 2025 and December 31, 2024, the Company’s marketable securities consist of debt securities, including U.S. Treasury and agency securities, corporate debt securities and commercial paper. These marketable securities are carried at fair value and are included in the tables above. The Company records an allowance for credit losses when unrealized losses are due to credit-related factors. At each reporting date, the Company evaluates securities with unrealized losses to determine whether such losses, if any, are due to credit-related factors. The Company evaluates, among others, whether the Company has the intention to sell any of these marketable securities and whether it is not more likely than not that the Company will be required to sell any of them before recovery of the amortized cost basis. Neither of these criteria were met at March 31, 2025 or December 31, 2024. The credit ratings of the securities held remain of the highest quality. Moreover, the Company continues to receive payments of interest and principal as they become due, and the Company's expectation is that those payments will continue to be received timely. Based on this evaluation, as of March 31, 2025 and December 31, 2024, the Company determined that unrealized losses of its marketable securities were primarily attributable to changes in interest rates and non-credit related factors. As such, no allowances for credit losses were recorded at March 31, 2025 or December 31, 2024.

Interest receivable as of March 31, 2025 and December 31, 2024 was $1.1 million and $1.0 million, respectively, and is recorded as a component of prepaid expenses and other current assets on the Company’s condensed balance sheets.

As of March 31, 2025 and December 31, 2024, all marketable securities in an unrealized loss position had been in an unrealized loss position for less than 12 months. As of March 31, 2025, the Company held 41 marketable securities in an unrealized loss position. As of December 31, 2024, the Company held 36 marketable securities in an unrealized loss position.

As of March 31, 2025, the following table summarizes the amortized cost and the unrealized gains (losses) of the marketable securities presented within marketable securities and cash equivalents (in thousands):

	Remaining								Aggregate
	Contractual								Estimated Fair
	Maturity (in years)	Amortized Cost		Unrealized Gains		Unrealized Losses			Value
Commercial paper	Less than 1	$	114,030	$	—	$	(26	)	$	114,004
U.S. treasury securities	Less than 1		81,480		63		(2	)		81,541
U.S. government agency     securities	Less than 1		16,231		5		(2	)		16,234
Corporate debt securities	Less than 1		2,177		4		—			2,181
Total maturity less than 1 year			213,918		72		(30	)		213,960
U.S. treasury securities	1 to 2		59,112		130		—			59,242
U.S. government agency     securities	1 to 2		2,495		22		—			2,517
Corporate debt securities	1 to 2		479		4		—			483
Total		$	276,004	$	228	$	(30	)	$	276,202

10

SEPTERNA, INC.

Notes to UNAUDITED Condensed Financial Statements (CONTINUED)

As of December 31, 2024, the following table summarizes the amortized cost and the unrealized gains (losses) of the marketable securities presented within marketable securities and cash equivalents (in thousands):

	Remaining Contractual Maturity (in years)	Amortized Cost		Unrealized Gains		Unrealized Losses			Aggregate Estimated Fair Value
Commercial paper	Less than 1	$	106,017	$	6	$	(9	)	$	106,014
U.S. treasury securities	Less than 1		73,511		44		—			73,555
U.S. government agency     securities	Less than 1		22,245		10		(3	)		22,252
Corporate debt securities	Less than 1		1,491		1		—			1,492
Total maturity less than 1 year			203,264		61		(12	)		203,313
U.S. treasury securities	1 to 2		65,427		37		(58	)		65,406
U.S. government agency     securities	1 to 2		2,492		22		—			2,514
Corporate debt securities	1 to 2		1,940		7		(1	)		1,946
Total		$	273,123	$	127	$	(71	)	$	273,179

As of March 31, 2025, the following table summarizes marketable securities in an unrealized loss position (in thousands):

	Less than 12 Months
	Fair Value		Gross Unrealized Loss
Commercial paper	$	113,006	$	(26	)
U.S. treasury securities		22,086		(2	)
U.S. government agency securities		7,000		(2	)
Corporate debt securities		705		—
Total	$	142,797	$	(30	)

As of December 31, 2024, the following table summarizes marketable securities in an unrealized loss position (in thousands):

	Less than 12 Months
	Fair Value		Gross Unrealized Loss
Corporate debt securities	$	987	$	(1	)
Commercial paper		70,172		(9	)
U.S. government agency securities		6,469		(3	)
U.S. treasury securities		52,508		(58	)
Total	$	130,136	$	(71	)

Note 5. Commitments and Contingencies

Legal Proceedings

In the ordinary course of business, the Company may be subject to legal proceedings, claims and litigation, as the Company operates in an industry susceptible to patent or other legal claims. The Company is not currently a party to any legal proceeding that, if determined adversely to the Company, in management’s opinion, is expected to individually or in the aggregate have a material adverse effect on its business, financial condition or liquidity and results of operations.

Indemnifications

In the ordinary course of business, the Company enters into agreements that may include indemnification provisions. As permitted under Delaware law and in accordance with its bylaws, the Company indemnifies its officers and directors for certain events or occurrences while the officer or director is or was serving in such capacity. The Company is also party to indemnification agreements with its officers and directors.

11

SEPTERNA, INC.

Notes to UNAUDITED Condensed Financial Statements (CONTINUED)

The maximum potential amount of future payments that the Company could be required to make under these provisions is not determinable; however, the Company currently holds director and officer liability insurance. This insurance limits 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. In addition, the Company is not currently aware of any indemnification claims that could have a material effect on its condensed financial statements.

Note 6. Common Stock

As of March 31, 2025 and December 31, 2024, the Company was authorized to issue 500.0 million shares of common stock, par value $0.001 per share.

The Company reserved the following shares of common stock, on an as-converted basis, for future issuance:

	As of March 31,		As of December 31,
	2025		2024
Options issued and outstanding		3,194,657		2,938,982
Shares reserved for future grants under 2024 Stock Option    and Incentive Plan		5,683,435		3,743,915
Shares reserved for issuance under 2024 Employee Stock Purchase Plan		369,402		369,402
		9,247,494		7,052,299

Note 7. Stock-Based Compensation

Stock Plans

In October 2024, the Company’s board of directors adopted, and its stockholders approved, the 2024 Option and Incentive Plan (the “2024 Plan”), which superseded the Company’s 2021 Stock Option and Grant Plan, as amended (the “2021 Plan”), (together, the “Stock Plans”).

On January 1, 2025, 2.2 million shares of common stock, representing 5% of the Company’s outstanding shares of common stock as of December 31, 2024, were added to the 2024 Plan. As of March 31, 2025, there were 5.7 million shares available for issuance under the 2024 Plan.

2024 ESPP

In October 2024, the Company’s board of directors adopted, and its stockholders approved, the 2024 Employee Stock Purchase Plan (the “2024 ESPP”), which became effective immediately prior to the effective date of the Company's IPO.

As of March 31, 2025, the Company has issued no shares under the 2024 ESPP as the first offering period has not begun. As of March 31, 2025, there were 0.4 million shares available for issuance under the 2024 ESPP.

Restricted Stock Awards

The following summarizes restricted stock award activity:

	Number of Shares Outstanding			Weighted-Average Grant Date Fair Value Per Share
Balance at December 31, 2024		576,829		$	2.62
Restricted stock awards vested		(119,730	)		2.93
Balance at March 31, 2025		457,099			2.53

12

SEPTERNA, INC.

Notes to UNAUDITED Condensed Financial Statements (CONTINUED)

Restricted stock awards of 457,099 and 576,829 shares were subject to repurchase as of March 31, 2025 and December 31, 2024, respectively. The aggregate grant date fair value of shares vested during the three months ended March 31, 2025 was $0.4 million.

Stock Options

The following summarizes stock option activity under the Stock Plans:

	Stock Options Outstanding
	Total Stock Options Outstanding			Weighted-Average Exercise Price		Weighted-Average Remaining Contractual Life		Aggregate Intrinsic Value
						(in years)		(in thousands)
Outstanding as of December 31, 2024		2,938,982		$	4.64		9.11	$	53,706
Granted		304,400			12.32
Exercised		(25,930	)		2.58
Cancelled		(22,795	)		5.50
Outstanding as of March 31, 2025		3,194,657			5.38		8.83		5,092
Exercisable as of March 31, 2025		670,369			3.18		8.00		1,835

The aggregate fair value of stock options that vested for the three months ended March 31, 2025 was $0.8 million. The stock options granted in the three months ended March 31, 2025 had a weighted-average grant-date fair value per share of $9.32 and a total grant-date fair value of $2.8 million. The total intrinsic value of stock options exercised during three months ended March 31, 2025 was $0.3 million.

Of the total stock options granted during the three months ended March 31, 2025, options to purchase 0.2 million shares granted to one of the Company's officers include accelerated vesting provisions associated with certain change of control events.

Stock Option Valuation

The weighted-average assumptions used to value employee and non-employee stock option awards granted under the Stock Plans using the Black Scholes option pricing model, were as follows:

	Three Months Ended March 31,
	2025			2024
Fair value of common stock	$	9.32		$	2.77
Risk-free interest rate		4.35	%		4.25	%
Expected volatility		88.6	%		92.0	%
Expected term (years)		5.99			5.99
Expected dividend yield	—%			—%

Stock-based Compensation Expense

Stock-based compensation expense for restricted stock awards and stock options recognized in the Company’s condensed statements of operations and comprehensive loss is presented as follows (in thousands):

	Three Months Ended March 31,
	2025		2024
Research and development expense	$	662	$	297
General and administrative expense		820		280
Total stock-based compensation expense	$	1,482	$	577

As of March 31, 2025, total unrecognized stock-based compensation expense related to unvested restricted stock awards and unvested stock options was $16.2 million, which is expected to be recognized over a weighted-average period of 2.8 years.

13

SEPTERNA, INC.

Notes to UNAUDITED Condensed Financial Statements (CONTINUED)

Note 8. Related Parties

Third Rock Ventures

In August 2021, the Company entered into a service agreement (the “TRV service agreement”) with Third Rock Ventures, LLC (“TRV”), a holder of more than 5% of the Company’s outstanding capital stock, under which TRV provides consulting services to the Company. For the three months ended March 31, 2025, the Company incurred no fees under the TRV service agreement. For the three months ended March 31, 2024, under the TRV service agreement, the Company incurred fees of less than $0.1 million which were recorded within general and administrative expenses in the Company’s condensed statements of operations and comprehensive loss. As of December 31, 2024, $0.1 million of expense related to TRV was recorded in accrued expenses and other current liabilities. There were no expenses related to TRV in accrued expenses and other current liabilities on the Company’s condensed balance sheets at March 31, 2025.

The Company’s former interim Chief Medical Officer, and also a member of the Company’s board of directors, is affiliated with TRV (the “Board Member”). The Board Member did not receive any cash compensation from the Company for his service as its interim Chief Medical Officer, as his services were provided to the Company through the TRV service agreement. The Board Member ceased serving as interim Chief Medical Officer in September 2024. In December 2024, the Company entered into a separate consulting agreement with the Board Member, which includes cash compensation paid directly to the Board member.

Of the total fees the Company incurred under the TRV service agreement for three months ended March 31, 2024, the fees attributed to consulting services provided by the Board Member as the interim Chief Medical officer were not material. Additionally, as compensation for his services as the Company's interim Chief Medical Officer, the Company granted him options to purchase 23,227 shares during the three months ended March 31, 2024, at an exercise price of $2.76 per share.

During the three months ended March 31, 2025, total fees incurred related to the Board Member’s consulting services were not material and were recorded in accrued expenses and other current liabilities.

Note 9. Net Loss Per Share

For all periods presented, diluted net loss per share is the same as basic net loss per share since the effect of including potential common shares is anti-dilutive. Potentially dilutive securities not included in the calculation of diluted net loss per share were as follows (in common stock equivalent shares):

	As of March 31,		As of March 31,
	2025		2024
Outstanding stock options		3,194,657		1,816,051
Unvested restricted stock subject to repurchase		457,099		813,966
Total antidilutive securities		3,651,756		2,630,017

Note 10. Segment Information

The Company operates in one segment, which is GPCR oral small molecule drug discovery. The Company’s Chief Operating Decision Maker (“CODM”) is its Chief Executive Officer. The measure of segment profit or loss is net loss, which is also reported on the condensed statements of operations and comprehensive loss as net loss.

The measure of segment assets is reported on the balance sheet as total assets. The CODM uses segment net loss to monitor spending, assess performance for the Company and management, evaluate the progress of completing corporate goals, decide how to allocate resources among the Company’s clinical and pre-clinical portfolios, and make strategic decisions about business development opportunities.

14

SEPTERNA, INC.

Notes to UNAUDITED Condensed Financial Statements (CONTINUED)

The CODM is regularly provided with the following significant segment expenses:

	Three Months Ended March 31,
	2025			2024
Revenue	$	219		$	317
Employee-related expenses, excluding stock-based compensation		6,845			4,440
Stock-based compensation		1,482			577
External research and development expenses		10,239			6,192
External general and administrative expenses		2,652			855
Other segment expenses*		4,911			3,743
Total operating expenses		26,129			15,807
Loss from operations		(25,910	)		(15,490	)
Other income, net		4,434			1,231
Loss before provision for income taxes		(21,476	)		(14,259	)
Benefit for income taxes		—			93
Net loss	$	(21,476	)	$	(14,166	)

(*) Other segment expenses include facility related and office costs, information technology costs, general laboratory costs, and other operating expenses.

As of March 31, 2025 and December 31, 2024, all of the Company’s property and equipment was maintained in the U.S. For the three months ended March 31, 2025 and 2024, the Company’s revenue was generated from providing research services and was earned in the U.S.

Note 11. Subsequent Event

Novo Collaboration Agreement

On May 13, 2025, the Company entered into a global Collaboration and License Agreement (the “Collaboration Agreement”) with Novo Nordisk A/S (“Novo”). Under the Collaboration Agreement, the Company and Novo will exclusively collaborate to leverage the Company’s proprietary Native Complex Platform™ to discover, develop and commercialize multiple potential oral small molecule therapies for metabolic-related diseases based on certain specified molecular targets.

The Company and Novo will initially commence four simultaneous research and development programs (each an “R&D Program”) with each pursuing one or more Collaboration Targets (as defined in the Collaboration Agreement) from discovery through development candidate selection. Beginning with investigational new drug-enabling activities, Novo will then be responsible for all further global development and commercialization for each product candidate at its sole cost and expense. Novo will reimburse the Company for 100% of the fully burdened costs arising from all research and development activities undertaken by the Company under the Collaboration Agreement. Novo is also responsible for all commercialization costs subject to the Company’s profit share option described below for up to one program under the collaboration. Pursuant to the terms of the Collaboration Agreement, the Company will provide Novo with exclusive licenses to enable Novo to develop and commercialize products directed at the Collaboration Targets. The Company retains all other rights to its Native Complex Platform™ and all of the Company’s other research and development programs.

The effective date of the Collaboration Agreement is subject to the expiration or early termination of the waiting period (and any extension thereof) under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as well as standard closing conditions. Within a specified period of time following the effectiveness of the Collaboration Agreement, Novo will pay the Company a one-time, non-refundable upfront payment of $195.0 million. For each R&D Program, the Company is also eligible to receive up to $498.0 million in research, development, regulatory, and commercial milestone payments. In addition, the Company is entitled to escalating, tiered royalties ranging from mid to high single-digits based on global product sales on a country-by-country and product-by-product basis. The Company is in the process of assessing the accounting treatment of the Collaboration Agreement.

Unless earlier terminated, the term of the Collaboration Agreement continues until expiration of the last royalty term for the applicable product in the applicable country. The Collaboration Agreement is subject to customary termination provisions, including termination by a party for the other party’s uncured, material breach. The Collaboration Agreement also includes customary representations and warranties, covenants and indemnification obligations.

15

Item 2. 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 unaudited interim condensed financial statements and related notes included elsewhere in this Quarterly Report and audited financial statements and notes thereto as of and for the year ended December 31, 2024 and the related Management’s Discussion and Analysis of Financial Condition and Results of Operations, both of which are contained in our Annual Report on Form 10-K for the year ended December 31, 2024 (“Annual Report”), filed with the Securities and Exchange Commission (the “SEC”) on March 27, 2025. This discussion and other parts of this Quarterly Report contain forward-looking statements based upon current beliefs, plans, and expectations related to future events and our future financial performance that involve risks, uncertainties and assumptions, such as statements of our plans, objectives, expectations, intentions, forecasts and projections. Our actual results and the timing of selected events could differ materially from those discussed in these forward-looking statements as a result of several factors including, but not limited to, those set forth under the section titled “Risk Factors” and elsewhere in this Quarterly Report. Our historical results are not necessarily indicative of the results that may be expected for any period in the future, and you should carefully read the section titled “Risk Factors” to gain an understanding of the important factors that could cause actual results to differ materially from our forward-looking statements. Please also see the section titled “Special Note Regarding Forward-Looking Statements.”

Overview

We are a biotechnology company pioneering a new era of G protein-coupled receptor (“GPCR”) oral small molecule drug discovery powered by our proprietary Native Complex Platform™. Our industrial-scale platform aims to unlock the full potential of GPCR therapies and has led to the discovery and development of our deep pipeline of product candidates focused initially on treating patients in three therapeutic areas: endocrinology, immunology and inflammation, and metabolic diseases.

Our proprietary Native Complex Platform™ replicates the natural structure, function, and dynamics of GPCRs outside of cells at an industrial scale for, as we believe it, the first time. Our foundational technologies enable us to isolate, purify, and reconstitute full-length, properly folded GPCR proteins within ternary complexes with ligands and transducer proteins in a lipid bilayer that mimics the cell membrane. We then apply state-of-the-art discovery tools and technologies to these defined and tunable protein complexes to structurally design, screen for, and optimize potential product candidates. Leveraging our platform, we conduct GPCR oral small molecule drug discovery using an industrialized and iterative structure-based drug design approach for a diverse collection of GPCR targets. Our Native Complex Platform™ is designed to enable us to target specific GPCRs, uncover novel binding pockets for validated receptors, and pursue a wide spectrum of pharmacologies, including agonists (which activate GPCR signaling), antagonists (which inhibit GPCR signaling), and allosteric modulators (which either increase or decrease the degree of GPCR activation by endogenous ligands), to affect GPCR signaling in different ways to achieve desired therapeutic effects.

We are advancing a deep portfolio of oral small molecule GPCR-targeted programs with novel mechanistic approaches to treat diseases across multiple therapeutic areas for patients with significant unmet needs. Our wholly-owned pipeline, summarized in the figure below, is focused initially on three therapeutic areas: endocrinology, immunology and inflammation, and metabolic diseases.

16

Financial Overview

We were incorporated in Delaware in December 2019 under the name GPCR NewCo, Inc. In June 2021, we changed our name to Septerna, Inc. We are headquartered in South San Francisco, California.

We have incurred significant operating losses since our inception, except for the year ended December 31, 2023, when we recorded net income of $4.2 million, resulting from the gain on sale of non-financial asset of $47.6 million for the sale of an in-progress research and development (“IPR&D”) asset related to a GPCR program. Our revenue to date has been generated solely from research services. Since our founding, we have devoted substantially all of our resources to organizing and staffing our company, business planning, raising capital, developing our proprietary and structure-based drug discovery platform, identifying and discovering our product candidates, establishing our intellectual property portfolio, conducting research and preclinical studies, including investigational new drug (“IND”)-enabling studies, initiating and conducting clinical trials, establishing arrangements with third parties for the manufacture of our product candidates and related raw materials, and providing general and administrative support for these operations. We have not had any products approved for sale and have not generated any revenue from product sales. Further, we do not expect to generate revenue from commercial product sales until such time, if ever, that we are able to successfully complete the development and obtain marketing approval for one or more of our product candidates. Our ability to generate product revenue will depend on the successful development and eventual commercialization of one or more of our product candidates.

Our net loss was $21.5 million and $14.2 million for the three months ended March 31, 2025 and 2024, respectively. As of March 31, 2025, we had an accumulated deficit of $139.9 million. We have incurred net losses in each year since inception, except for the year ended December 31, 2023. We expect to continue to incur net losses for the foreseeable future. Our net losses may fluctuate significantly from period to period, depending on the timing and expenditures of our operational activities.

We expect to continue to incur significant and increasing net operating losses for the next several years as we:

•continue to advance our product candidates through preclinical studies and into clinical trials;

•attract, hire and retain additional personnel;

•continue to operate as a public company, including expenses related to compliance with the rules and regulations of the SEC and those of any national securities exchange on which our securities are traded, legal, auditing, additional insurance expenses, investor relations activities, and other administrative and professional services;

•continue our research and development efforts and expand our pipeline of product candidates;

•acquire, discover, validate, and develop additional product candidates;

•require the manufacture of supplies for our preclinical studies and clinical trials;

•obtain, maintain, expand, and protect our intellectual property portfolio;

•implement operational, financial and information management systems;

•make royalty, milestone or other payments under any future, license or collaboration agreements;

•potentially seek to identify, assess, acquire, or in-license or develop new technologies or additional product candidates;

•potentially experience any delays, challenges, or other issues associated with the clinical development of our product candidates, including with respect to our regulatory strategies;

•pursue regulatory approval of product candidates that successfully complete clinical trials; and

•establish a sales, marketing and distribution infrastructure to commercialize any product candidate for which we may obtain marketing approval and related commercial manufacturing build-out.

Our net losses may fluctuate significantly from period to period, depending upon the timing of our expenditures on research and development activities. Cash used to fund operating expenses is impacted by the timing of when we pay these expenses, as reflected in the change in our accounts payable and accrued expenses and other current liabilities, which includes accrued research and development, in the statements of cash flows in our audited and unaudited interim condensed financial statements included elsewhere in this Quarterly Report.

As a result, we will require substantial additional funding to further develop our product candidates and support our continuing operations. Until such time, if ever, as we can generate substantial product revenue, we expect to finance our operations through a combination of equity offerings, debt financings, collaborations, strategic alliances and marketing, distribution or licensing

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arrangements. See the section titled “Liquidity and Capital Resources - Future Funding Requirements” below for additional information.

We historically financed our operations primarily through the issuances of convertible promissory notes and convertible preferred stock, and, most recently, through an initial public offering (“IPO”). In October 2024, we completed our IPO, pursuant to which we issued and sold an aggregate of 18.4 million shares of our common stock (inclusive of an additional 2.4 million shares of our common stock issued and sold pursuant to the underwriters' exercise of their option to purchase additional shares in full). The aggregate net proceeds received by us from the IPO was $302.8 million, net of total offering costs of $28.4 million.

Since our inception, we have devoted substantially all of our resources to raising capital, organizing and staffing our company, business and scientific planning, conducting discovery and research and development activities, establishing and protecting our intellectual property portfolio, developing and progressing our product candidates and preparing for clinical trials, establishing arrangements with third parties for the manufacture of our product candidates and component materials, engaging in collaboration activities, and providing general and administrative support for these operations.

We use contract research and development organizations to conduct our preclinical work and clinical trials. Additionally, we utilize third-party contract manufacturing organizations (“CMOs”), to manufacture and supply our preclinical and clinical materials during the development of our product candidates. We expect to use similar contract resources for the commercialization of our products, at least until our resources and operations are at a scale that justifies investment in internal manufacturing capabilities.

We conduct research and manufacturing work outside of the United States, including China, that may be affected by tariffs, including tariffs that have been or may in the future be imposed by the United States or other countries through reciprocal tariffs. While we do not currently believe tariffs will have a material impact on our business or results of operations, we will continue to carefully monitor the situation.

Vertex Asset Purchase and Service Agreements

Asset Purchase Agreement

In September 2023, we entered into an asset purchase agreement with Vertex Pharmaceuticals Incorporated (“Vertex”) under which Vertex acquired all of our IPR&D asset related to a GPCR program. The transfer of the IPR&D asset to Vertex was completed in November 2023.

At the same time in September 2023, we entered into a research service agreement with Vertex under which we agreed to perform certain exploratory research activities for Vertex. See the subsection titled “—Service Agreement” below.

The Vertex purchase agreement also provides for a potential milestone payment payable to us contingent upon achievement of a certain research milestone. The milestone payment amount is determined based on the timing of achievement of the research milestone. The variable consideration related to this milestone payment was determined to be improbable of receipt at this time. As a result, the milestone payment was excluded from the transaction price. After the potential milestone payment, we will not receive any other payments or future royalties related to this IPR&D asset.

Service Agreement

In addition to the Vertex purchase agreement, we also entered into a research service agreement with Vertex (“Vertex service agreement”) under which we agreed to perform certain exploratory research activities for Vertex. The Vertex service agreement is for a two-year term, however, Vertex has the ability to terminate the agreement with a 30-day notice at any time. As a result, we concluded that the contract duration is 30 days, representing a month-to-month service contract. We recognize revenue associated with the Vertex service agreement over the performance period of the research services as the services are provided.

Recent Developments

Novo Collaboration Agreement

On May 13, 2025, we entered into a global Collaboration and License Agreement (the “Collaboration Agreement”) with Novo Nordisk A/S (“Novo”). Under the Collaboration Agreement, we and Novo will exclusively collaborate to leverage our proprietary Native Complex Platform™ to discover, develop and commercialize multiple potential oral small molecule therapies for metabolic-related diseases based on certain specified molecular targets. The collaboration objective is to discover and develop several novel mono-, dual-, or triple-acting oral small molecule drug candidates directed across five GPCRs, including the GLP-1, GIP, and glucagon receptors (the “Collaboration Targets”). The collaboration includes our most advanced preclinical metabolic program focused on developing an

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oral small molecule agonist to the GIP receptor. We and Novo will initially commence four simultaneous research and development programs (each an “R&D Program”) with each pursuing one or more Collaboration Targets from discovery through development candidate selection.

The Collaboration Agreement includes potential payments to us exceeding $2.2 billion. Novo will pay us a one-time, non-refundable upfront payment of $195.0 million. For each R&D Program, we are also eligible to receive approximately $500.0 million in research, development, regulatory, and commercial milestone payments. In addition, we are entitled to escalating, tiered royalties ranging from mid-to-high single-digits based on global product sales on a country-by-country and product-by-product basis with respect to a R&D Program until the later of ten years after the date of first commercial sale of the first product in such R&D Program in such country, expiration of specified patent rights covering such product in such country or the expiration of specified regulatory exclusivity for the first product in such R&D Program in such country. See Note 11 to the condensed financial statements included elsewhere in this Quarterly Report for additional information.

Components of Results of Operations

Revenue

We have not generated any revenue from product sales and do not expect to do so in the foreseeable future. Our ability to generate product revenue, if ever, will depend on the successful development and eventual commercialization of any product candidates that we identify. If we fail to complete the development of any future product candidates in a timely manner or to obtain regulatory approval for such product candidates, our ability to generate future revenue and our results of operations and financial position would be materially adversely affected. Our revenues to date have been exclusively related to research services. We recognize revenue as specified research services are performed and the results of the research and development services are provided to the customer.

Operating Expenses

Our operating expenses consist of (i) research and development expenses and (ii) general and administrative expenses.

Research and Development

Research and development expenses account for the largest component of our total operating expenses. Research and development expenses consist primarily of direct and unallocated costs incurred for the research and development of our product candidates.

Our research and development expenses consist of:

•direct costs, including:

▪preclinical and research program costs, which include external research and development costs related to (i) the production of preclinical materials, including fees and milestones paid to contract manufacturers and (ii) agreements with contract development organizations, consultants and other third-party contract organizations to conduct our preclinical studies and other research and development activities on our behalf, costs incurred in connection with laboratory operations, materials and supplies, and other preclinical studies;

▪clinical program costs, which include external costs to conduct clinical trials, including costs paid to contract research organizations (“CROs”), the production of clinical materials and fees paid to contract manufacturers, costs incurred in connection with clinical laboratory operations, materials and supplies; and

•unallocated costs, including:

▪payroll-related costs, including salaries, benefits and stock-based compensation for employees engaged in research and development activities;

▪external research and development costs, including contract research and development and professional service fees for consulting and related services;

▪facility-related and office costs, including lease/rent, building-related expenses, facility-related overhead, and depreciation expense; and

▪other costs, including expenses related to our funded, sponsored research activities and technology licenses, laboratory operations, information technology (“IT”)-related expenses.

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We expense all research and development costs in the periods in which they are incurred. Costs for certain development activities are recognized based on an evaluation of the progress to completion of specific tasks using information and data provided to us by our vendors and third-party service providers.

A significant portion of our research and development costs have been external costs, which we track by stage of development. However, we do not track our unallocated costs on a program specific basis because these costs are deployed across multiple projects and, as such, are not separately classified.

At this time, we cannot reasonably estimate or know the nature, timing, and estimated costs of the efforts that will be necessary to complete the development of, and obtain regulatory approval for, any of our product candidates. We expect that our research and development expenses will increase substantially in absolute dollars for the foreseeable future as we continue to invest in research and development activities related to developing our product candidates, as our product candidates advance into later stages of development, as we begin to conduct clinical trials, as we seek regulatory approvals for any product candidates that successfully complete clinical trials, and as we incur expenses associated with hiring additional personnel to support our research and development efforts. The process of conducting the necessary clinical research to obtain regulatory approval is costly and time-consuming, and the successful development of our product candidates is highly uncertain. This is due to the numerous risks and uncertainties associated with developing product candidates, many of which are outside of our control, including the uncertainty of:

•the timing and progress of preclinical and clinical development activities;

•the number and scope of preclinical and clinical programs we decide to pursue;

•our ability to maintain our current research and development programs and to establish new ones;

•establishing an appropriate safety profile with IND-enabling studies;

•the number of sites and patients included in the clinical trials;

•the countries in which the clinical trials are conducted;

•per patient trial costs;

•successful patient enrollment in, and the initiation of, clinical trials, as well as drop out or discontinuation rates;

•the successful completion of clinical trials with safety, tolerability and efficacy profiles that are satisfactory to the U.S. Food and Drug Administration (the "FDA"), European Medicines Agency (“EMA”), or any other comparable foreign regulatory authorities;

•the number of trials required for regulatory approval;

•the timing, receipt and terms of any regulatory approvals from applicable regulatory authorities;

•our ability to maintain and establish collaboration arrangements;

•the performance of any current or future collaborators;

•establishing commercial manufacturing capabilities or making arrangements with third-party manufacturers;

•significant and changing government regulation and regulatory guidance;

•the impact of any business interruptions to our operations or to those of the third parties with whom we work;

•obtaining, maintaining, defending and enforcing patent claims and other intellectual property rights;

•launching commercial sales of our product candidates, if approved, whether alone or in collaboration with others; and

•maintaining a continued acceptable safety profile of the product candidates following approval.

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Any changes in the outcome of any of these variables could mean a significant change in the costs and timing associated with the development of our product candidates. For example, if the FDA, EMA or any other comparable foreign regulatory authority were to require us to conduct clinical trials beyond those that we anticipate will be required for the completion of clinical development of a product candidate, or if we experience significant delays in our clinical trials due to patient enrollment or other reasons, we would be required to expend significant additional financial resources and time on the completion of clinical development. We may never obtain regulatory approval for any of our product candidates.

General and Administrative

General and administrative expenses consist primarily of personnel-related costs, costs related to maintenance and filing of intellectual property, legal fees related to corporate matters, professional fees paid for accounting, auditing, consulting, tax and investor relations services, insurance costs, general corporate expenses, and IT-related and facility-related costs not otherwise included in research and development expenses. Personnel-related costs include salaries, benefits, and stock-based compensation for our personnel in executive, legal, finance and accounting, human resources, and other administrative functions.

We expect that our general and administrative expenses will increase substantially in absolute dollars for the foreseeable future as we continue to increase our headcount to support our business growth and to advance our research and development programs.

Other Income, Net

Interest Income

Interest income consists of interest earned on our cash, cash equivalents and marketable securities during the period.

Other Expense, Net

Other expense, net consists primarily of changes in the fair value of our cash equivalents held in money market funds, loss on disposal of our fixed assets and foreign currency transaction gain or loss.

Benefit for Income Taxes

We are subject to corporate United States federal and state income taxation. Our benefit for income taxes is recorded in accordance with Accounting Standard Codification 740, Accounting for Income Taxes, which provides for deferred taxes using an asset and liability approach. We establish a valuation allowance against all of our net deferred tax assets. We consider all available evidence, both positive and negative, including but not limited to our historical operating results, income or loss in recent periods, cumulative losses in recent years, forecasted earnings (losses), future taxable income (loss), and significant risk and uncertainty related to forecasts, and concluded the deferred tax assets are not more likely than not to be realized.

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Results of Operations

Comparison of the Three Months Ended March 31, 2025 and 2024

Our results of operations for each of the periods indicated are summarized in the table below (in thousands):

	Three Months Ended March 31,
	2025			2024			Change
Revenue	$	219		$	317		$	(98	)
Operating expenses:
Research and development		19,271			13,153			6,118
General and administrative		6,858			2,654			4,204
Total operating expenses		26,129			15,807			10,322
Loss from operations		(25,910	)		(15,490	)		(10,420	)
Other income, net:
Interest income		4,462			1,279			3,183
Other expense, net		(28	)		(48	)		20
Total other income, net		4,434			1,231			3,203
Loss before benefit for income taxes		(21,476	)		(14,259	)		(7,217	)
Benefit for income taxes		—			93			(93	)
Net loss	$	(21,476	)	$	(14,166	)	$	(7,310	)

Revenue

Our service revenue of $0.2 million and $0.3 million for the three months ended March 31, 2025 and 2024, respectively, was generated from research activities performed for Vertex in connection with the Vertex service agreement.

Operating Expenses

Research and Development

The following table summarizes our research and development expenses for the periods indicated by direct and unallocated costs (in thousands):

	Three Months Ended March 31,
	2025		2024		Change
Direct costs:
PTH1R	$	4,209	$	2,015	$	2,194
SEP-631 (MRGPRX2)		1,022		440		582
Other programs		4,200		1,127		3,073
Unallocated costs:
Payroll-related costs		5,413		3,681		1,732
External research and development costs		1,246		3,054		(1,808	)
Facility-related and office costs		1,926		1,173		753
Other costs		1,255		1,663		(408	)
Total research and development expense	$	19,271	$	13,153	$	6,118

Research and development expenses were $19.3 million and $13.2 million for the three months ended March 31, 2025 and 2024, respectively. The increase was primarily due to (i) $5.8 million of higher direct costs associated with our clinical and preclinical and research programs, including $1.7 million of clinical trial expenses, (ii) $1.7 million of higher employee-related costs as a result of increased headcount as we grow our business, and (iii) $0.8 million of higher facility-related and office costs as we expanded our office space to accommodate higher occupancy and larger operational activities, partially offset by (i) $1.8 million of lower expenses attributable to unallocated external research and development costs and (ii) a decrease of $0.4 million in other research and development expense.

The SEP-786 clinical study was discontinued in February 2025 and we do not anticipate incurring significant additional clinical trial costs associated with that study. We expect to continue to incur increased research and development expenses as we advance

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next-generation oral small molecule PTH1R agonists from our PTH1R program toward clinical development, advance SEP-631 (MRGPRX2) into clinical development, and continue to advance other programs in our pipeline.

General and Administrative

General and administrative expenses were $6.9 million and $2.7 million for the three months ended March 31, 2025 and 2024, respectively. The increase was primarily due to (i) $2.0 million of higher legal and consulting fees, mainly attributable to costs associated with becoming a public company and ongoing operations as a public company following our IPO in October 2024, (ii) $1.5 million of higher employee-related costs as a result of increased headcount to support our growing operations, and (iii) $0.4 million of higher IT operational expenses.

Other Income, Net

Interest Income

Interest income was $4.5 million and $1.3 million for the three months ended March 31, 2025 and 2024, respectively. The increase was due to higher interest rates and higher balances of invested cash in cash equivalents and marketable securities.

Benefit for Income Taxes

We recognized $0.1 million of benefit for income taxes for the three months ended March 31, 2024. We did not record any benefit or provision for income taxes for the three months ended March 31, 2025.

Liquidity and Capital Resources

Sources of Liquidity

Our net losses were $21.5 million and $14.2 million for the three months ended March 31, 2025 and 2024, respectively. As of March 31, 2025, we had an accumulated deficit of $139.9 million. We expect to continue to incur net losses for the foreseeable future. Our net losses may fluctuate significantly from period to period, depending on the timing and expenditures of our operational activities.

We historically financed our operations primarily through the issuances of convertible promissory notes and convertible preferred stock, and most recently, through an IPO. In October 2024, we completed our IPO, pursuant to which we issued and sold an aggregate of 18.4 million shares of common stock (inclusive of 2.4 million shares of common stock sold pursuant to the underwriters' exercise of their option to purchase additional shares in full). The aggregate net proceeds received by us from the IPO was $302.8 million, net of total offering costs of $28.4 million. As of March 31, 2025, we had $398.2 million in cash, cash equivalents, and marketable securities.

In May 2025, we entered into the Collaboration Agreement with Novo, pursuant to which we and Novo will exclusively collaborate to leverage our proprietary Native Complex Platform™ to discover, develop and commercialize multiple potential oral small molecule therapies for metabolic-related diseases based on certain specified molecular targets. Under the terms of the Collaboration Agreement, we are eligible to receive potential payments exceeding $2.2 billion, including more than $200.0 million in upfront and near-term milestone payments, along with tiered royalties on global net sales of marketed products. The anticipated upfront payment from the Collaboration Agreement is expected to significantly extend our prior cash runway guidance of early 2028, and updated guidance will be provided following the closing of the Collaboration Agreement. See Note 11 to the condensed financial statements included elsewhere in this Quarterly Report for additional information.

Cash Flows

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

	Three Months Ended March 31,
	2025			2024
Net cash used in operating activities	$	(23,343	)	$	(16,711	)
Net cash (used in) provided by investing activities		(4,874	)		9,568
Net cash provided by financing activities		66			—
Net increase in cash, cash equivalents and restricted cash	$	(28,151	)	$	(7,143	)

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Net Cash Used in Operating Activities

Net cash used in operating activities was $23.3 million and $16.7 million for the three months ended March 31, 2025 and 2024, respectively. The net cash used in operating activities for the three months ended March 31, 2025 was due to our net loss of $21.5 million and a $3.3 million of net change in operating assets and liabilities, partially offset by $1.4 million of non-cash charges for depreciation and amortization, stock-based compensation, non-cash operating lease expense, deferred income tax and accretion of discounts, net, on marketable securities.

The net cash used in operating activities for the three months ended March 31, 2024 was due to our net loss of $14.2 million and $3.5 million of net change in operating assets and liabilities, partially offset by $1.0 million of non-cash charges for depreciation and amortization, stock-based compensation and non-cash operating lease expense.

Net Cash (Used in) Provided by Investing Activities

Net cash used in investing activities of $4.9 million for the three months ended March 31, 2025 was due to $49.7 million of purchases of marketable securities and $0.4 million of purchases of property and equipment, partially offset by the maturity of $45.2 million of marketable securities.

Net cash provided by investing activities of $9.6 million for the three months ended March 31, 2024 was due to $22.6 million proceeds from the sale of non-financial asset, partially offset by the purchase of $12.3 million of marketable securities and $0.7 million of purchases of property and equipment.

Net Cash Provided by Financing Activities

Net cash provided by financing activities was $0.1 million for the three months ended March 31, 2025. Net cash provided by financing activities for the three months ended March 31, 2025 was due to proceeds from the exercise of stock options. Cash provided by financing activities during the three months ended March 31, 2024 was not material.

Future Funding Requirements

Our primary use of cash is to fund our operations, primarily research and development expenditures. Cash used for operating expenses is impacted by the timing of when we pay these expenses, as reflected in the change in our outstanding accounts payable, accrued expenses and prepaid expenses.

Because of the numerous risks and uncertainties associated with research, development and commercialization of pharmaceutical products, we are unable to estimate the exact amount of our operating capital requirements. Our future funding requirements will depend on many factors, including, but not limited to:

•the scope, timing, progress and results of discovery, preclinical development, laboratory testing and clinical trials for our product candidates;

•the expenses of manufacturing our product candidates for clinical trials and in preparation for marketing approval and commercialization;

•our ability to maintain collaborations or strategic relationships and the extent to which we identify and enter into future collaborations or other arrangements with additional third parties in order to further develop our product candidates;

•the expenses of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims;

•the expenses and fees associated with the discovery, acquisition or in-license of additional product candidates or technologies;

•our ability to establish additional collaborations on favorable terms, if at all;

•the expenses required to scale up our clinical, regulatory and manufacturing capabilities;

•the expenses of future commercialization activities, if any, including establishing sales, marketing, manufacturing and distribution capabilities, for any of our product candidates for which we receive marketing approval; and

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•revenue, if any, received from commercial sales of our product candidates, should any of our product candidates receive marketing approval.

We will need additional funds to meet operational needs and capital requirements for clinical trials, other research and development expenditures, and business development activities. Because of the numerous risks and uncertainties associated with the development and commercialization of our product candidates, we are unable to estimate the amounts of increased capital outlays and operating expenditures associated with our current and anticipated clinical studies.

Until such time, if ever, as we can generate substantial product revenue, we expect to finance our operations through a combination of equity offerings, debt financings, collaborations, strategic alliances and marketing, distribution or licensing arrangements. To the extent that we raise additional capital through the sale of equity or convertible debt securities, existing stockholders’ ownership interests will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect existing stockholders’ rights as common stockholders. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making acquisitions or capital expenditures or declaring dividends. If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates, or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings or other arrangements when needed, we may be required to delay, limit, reduce or terminate our research, product development or future commercialization efforts, or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

We historically financed our operations primarily through the issuances of convertible promissory notes and convertible preferred stock, and most recently, through an IPO. In October 2024, we completed our IPO which resulted in net proceeds of $302.8 million, net of total offering costs of $28.4 million. Since our inception, we have devoted substantially all of our resources to raising capital, organizing and staffing our company, business and scientific planning, conducting discovery and research and development activities, establishing, maintaining, and protecting our intellectual property portfolio, developing and progressing our product candidates and preparing for clinical trials, establishing arrangements with third parties for the manufacture of our product candidates and component materials, engaging in collaboration activities, and providing general and administrative support for these operations.

Critical Accounting Policies and Use of Estimates

Management’s discussion and analysis of our financial condition and results of operations is based on our condensed financial statements, which have been prepared in accordance with generally accepted accounting principles in the United States (“U.S. GAAP”). The preparation of these condensed 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 condensed financial statements, as well as the reported revenue generated and 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 and any such differences may be material. We believe that the accounting policies discussed below are critical to understanding our historical and future performance, as these policies relate to the more significant areas involving management’s judgments and estimates.

During the three months ended March 31, 2025, there have been no material changes to our critical accounting policies and estimates as described in our Annual Report.

Recent Accounting Pronouncements

A description of recently issued accounting pronouncements that may potentially impact our financial position and results of operations is disclosed in Note 1 to our condensed financial statements included elsewhere in this Quarterly Report.

Emerging Growth Company and Smaller Reporting Company Status

We qualify as “emerging growth company” under the JOBS Act, which permits us to take advantage of an extended transition period to comply with new or revised accounting standards. This provision allows an emerging growth company to delay the adoption of accounting standards that have different effective dates for public and private companies until those standards would otherwise apply to private companies. We have elected to use this extended transition period under the JOBS Act until the earlier of the date we (i) are no longer an emerging growth company or (ii) affirmatively and irrevocably opt out of the extended transition period provided in the JOBS Act. As a result, our financial statements may not be comparable to companies that comply with new or revised accounting pronouncements as of public company effective dates. We could be an emerging growth company until the earliest to occur: (i) the last day of the fiscal year in which we have more than $1.235 billion in annual gross revenue; (ii) the date we qualify as a “large accelerated

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filers” as defined in Rule 12b-2 under the Exchange Act, with at least $700.0 million of equity securities held by non-affiliates; (iii) the issuance, in any three-year period, by us of more than $1.0 billion in non-convertible debt securities; or (iv) the last day of the fiscal year ending after the fifth anniversary of our IPO. Even after we no longer qualify as an emerging growth company, we may continue to qualify as a “smaller reporting company,” which would allow us to take advantage of many of the same exemptions from disclosure requirements including reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements, if either (i) the market value of our stock held by non-affiliates is less than $250.0 million or (ii) our annual revenue is less than $100.0 million during the most recently completed fiscal year and the market value of our stock held by non-affiliates is less than $700.0 million.

Item 3. Quantitative and Qualitative Disclosures About Market Risk.

We are a smaller reporting company as defined by Rule 12b-2 of the Exchange Act and are not required to provide the information required under this item.

Item 4. Controls and Procedures.

Evaluation of Disclosure Controls and Procedures

Our management, with the participation of our Principal Executive Officer and Principal Financial Officer, has evaluated the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act), as of the end of the period covered by this Quarterly Report.

Based on such evaluation, our Principal Executive Officer and Principal Financial Officer have concluded that these disclosures controls were effective at a reasonable assurance level as of March 31, 2025.

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 the fiscal quarter ended March 31, 2025 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

Limitations on Effectiveness of Controls and Procedures

Our management, including our Principal Executive Officer and Principal Financial Officer, believes that our disclosure controls and procedures and internal control over financial reporting are designed to provide reasonable assurance of achieving their objectives and are effective at the reasonable assurance level. However, the effectiveness of any internal control over financial reporting is subject to inherent limitations, including the exercise of judgment in designing, implementing, operating, and evaluating the controls and procedures, and the inability to eliminate misconduct completely. Because of the inherent limitations in all control systems, no evaluation of controls can provide absolute assurance that all control issues and instances of fraud, if any, have been detected. The design of any system of controls is based in part on certain assumptions about the likelihood of future events, and there can be no assurance that any design will succeed in achieving its stated goals under all potential future conditions. Over time, controls may become inadequate because of changes in conditions or deterioration in the degree of compliance with policies or procedures. Because of the inherent limitations in a cost-effective control system, misstatements due to error or fraud may occur and not be detected.

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PART II—OTHER INFORMATION

Item 1. Legal Proceedings.

The information required with respect to this item can be found under “Legal Proceedings” in Note 5 to our condensed financial statements included elsewhere in this Quarterly Report on Form 10-Q (this “Quarterly Report”) and is incorporated by reference into this Item 1. From time to time, we may become involved in litigation or other legal proceedings. We are not currently a party to any litigation or legal proceedings that, in the opinion of our management, are probable to have a material adverse effect on our business. Regardless of outcome, litigation can have an adverse impact on our business, financial condition, results of operations and prospects because of defense and settlement costs, diversion of management resources and other factors.

Item 1A. Risk Factors.

Investing in our common stock involves a high degree of risk. For a detailed discussion of the risks and uncertainties related to our business, please refer to the section titled “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2024. There have been no material changes from the risk factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2024, except as set forth below. You should carefully consider the risks and uncertainties described below and in our Annual Report on Form 10-K for the year ended December 31, 2024, together with all of the other information contained in or incorporated by reference into this Quarterly Report, including our condensed financial statements and the related notes appearing at the end of this Quarterly Report and the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” before deciding to invest in our common stock. If any of the events or developments described below were to occur, our business, prospects, operating results and financial condition could suffer materially, the trading price of our common stock could decline and you could lose all or part of your investment. The risks and uncertainties described below are not the only ones we face. Additional risks and uncertainties not presently known to us or that we currently believe to be immaterial may also adversely affect our business. This Quarterly Report also contains forward-looking statements that involve risks and uncertainties. Our actual results could differ materially from those anticipated in the forward-looking statements as a result of a number of factors, including the risks described below. See the section titled “Special Note Regarding Forward-Looking Statements.”

Disruptions at the FDA and other government agencies caused by reduction in staffing, funding shortages or global health concerns could hinder their ability to hire, retain or deploy key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved or commercialized in a timely manner or at all, which could negatively impact our business.

Currently, federal agencies in the U.S. are operating under a continuing resolution that is set to expire on September 30, 2025 and the current U.S. administration is focused on reducing costs of the federal government generally, including significantly reducing the number of government employees. Without appropriation of additional funding to federal agencies, our business operations related to our product development activities for the U.S. market could be impacted. The ability of the FDA, EMA, and other comparable foreign regulatory authorities to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory, and policy changes. Average review times at the FDA have fluctuated in recent years as a result. In addition, government funding of other government agencies that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable. The Trump Administration has issued executive orders seeking to greatly reduce the size of the federal workforce, including through layoffs and severance packages offered to employees of federal agencies within the executive branch and independent agencies, including the FDA. Any such reduction in personnel may result in longer review times by the FDA and other agencies.

Disruptions and personnel turnover, as a result of leadership changes, staff reductions or otherwise, at the FDA and other agencies may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. Changes and cuts in FDA staffing also could result in delays in the FDA’s responsiveness or in its ability to review IND submissions or applications, issue regulations or guidance, or implement or enforce regulatory requirements in a timely fashion or at all. There is also substantial uncertainty as to how regulatory reform measures being implemented by the current U.S. administration, and other political developments, such as government shutdowns or work stoppages, would impact other U.S. regulatory agencies, such as the FDA, SEC and U.S. Patent and Trademark Office (“USPTO”), on which our operations rely. For example, in March 2025, the Department of Health and Human Services announced a broad-scale restructuring effort designed to significantly reduce FDA headcount. In April 2025, FDA employees began to receive reduction in force notices. In addition, over the last several years, the U.S. government shut down several times and certain regulatory agencies, such as the FDA and the SEC, furloughed critical employees and ceased critical activities. If a prolonged government shutdown occurs, or if staffing changes prevent the FDA, USPTO or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, including formal and informal interactions with product developers, it could significantly impact the ability of such regulatory agencies to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

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Unfavorable global economic conditions, political instability and geopolitical events could adversely affect our business, financial condition, stock price, and results of operations.

Our business could be adversely affected by unstable economic and political conditions within the United States and foreign jurisdictions, including as a result of an economic downturn and geopolitical events, such as changes in the U.S. federal policy that affect the geopolitical landscape. The global credit and financial markets have also generally experienced extreme volatility and disruptions (including as a result of actual or perceived changes in interest rates, inflation and macroeconomic uncertainties), which has included severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, high inflation, uncertainty about economic stability, global supply chain disruptions, and increases in unemployment rates. There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur. A severe or prolonged economic downturn could result in a variety of risks to our business, including a decrease in the demand for our product candidates and in our ability to raise additional capital when needed on acceptable terms, if at all.

The financial markets and the global economy may also be adversely affected by the current or anticipated impact of military conflicts, such as the ongoing conflicts between Russia and Ukraine, and Israel and Hamas, terrorism, or other geopolitical events. Sanctions imposed by the United States and other countries in response to such conflicts, including the one in Ukraine, may also continue to adversely impact the financial markets and the global economy, and any economic countermeasures by the affected countries or others could exacerbate market and economic instability. Additionally, changes to policy implemented by the U.S. Congress, the Trump administration or any new administration have impacted and may in the future impact, among other things, the U.S. and global economy, international trade relations, unemployment, immigration, healthcare, taxation, the U.S. regulatory environment, inflation and other areas. For example, during the prior Trump administration, increased tariffs were implemented on goods imported into the U.S., particularly from China, Canada, and Mexico. Additionally, in 2025, the United States imposed significant tariffs on imports from other countries, including a baseline tariff of 10% on imports into the United States and higher tariffs on multiple designated countries (including the EU Member States, China, Canada, and Mexico), such as "reciprocal" tariffs at varying rates. Such tariffs have prompted retaliatory measures from several countries, which may further escalate. On April 9, 2025, the United States announced that the imposition of most "reciprocal" tariffs would be paused for 90 days pending negotiations with the relevant countries. While pharmaceutical products are currently excluded from the baseline and "reciprocal" tariffs imposed by the United States, such tariffs still apply to the raw materials and other products necessary for the manufacture and formulation of our product candidates. In addition, the current U.S. administration has expressed an intent to impose tariffs on pharmaceutical imports, with the stated policy objective of reshoring pharmaceutical manufacturing to the United States. Among other means, such tariffs may be imposed by the United States under Section 232 of the Trade Expansion Act of 1962, as amended, pursuant to which the U.S. Department of Commerce recently initiated an investigation to determine the effects of importing pharmaceuticals and pharmaceutical ingredients on national security. In response to tariffs, other countries have implemented retaliatory tariffs on U.S. goods. Political tensions as a result of trade policies could reduce trade volume, investment, technological exchange and other economic activities between major international economies, resulting in a material adverse effect on global economic conditions and the stability of global financial markets. There has also been proposed United States legislation, such as the bill titled the BIOSECURE Act, that may restrict the ability of United States pharmaceutical companies to purchase services or products from, or otherwise collaborate with, certain Chinese biotechnology companies of concern without losing the ability to contract with, or otherwise receive funding from, the United States government. We continue to assess the legislation as it develops to determine whether it could have an effect on our contractual relationships. Any changes in political, trade, regulatory, and economic conditions, including U.S. trade policies, could have a material adverse effect on our financial condition or results of operations. Until we know what policy changes are made, whether those policy changes are challenged and subsequently upheld by the court system and how those changes impact our business and the business of our competitors over the long term, we will not know if, overall, we will benefit from them or be negatively affected by them.

Furthermore, any disruptions to our supply chain as a result of unfavorable global economic conditions, including due to geopolitical conflicts, could negatively impact the timely execution of our ongoing and future clinical trials. In addition, current inflationary trends in the global economy may impact salaries and wages, costs of goods and transportation expenses, among other things, and recent and potential future disruptions in access to bank deposits or lending commitments due to bank failures may create market and economic instability. We cannot anticipate all of the ways in which the foregoing, and the current economic climate and financial market conditions generally, could adversely impact our business.

Item 2. Unregistered Sales of Equity Securities and Use of Proceeds

Set forth below is information regarding shares of equity securities sold, and options granted, by us during the three months ended March 31, 2025 that were not registered under the Securities Act.

(a) Unregistered Sales of Equity Securities

None.

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(b) Use of Proceeds from our IPO

On October 24, 2024, our Registration Statement on Form S-1 (File No. 333-282469), as amended, relating to our IPO was declared effective by the Securities and Exchange Commission (the “SEC”) (the “Registration Statement”). Pursuant to the Registration Statement, we registered the offer and sale of 18,400,000 shares of our common stock. On October 28, 2024, we closed our IPO, pursuant to which we issued and sold 18.4 million shares of common stock at the public offering price of $18.00 per share, which included 2.4 million shares of our common stock issued and sold on October 30, 2024 to the underwriters pursuant to the full exercise of their option to purchase additional shares of our common stock, at the public offering price of $18.00 per share. Pursuant to the IPO, we received gross proceeds of $331.2 million, which resulted in net proceeds to us of $302.8 million, after deducting underwriting discounts and commissions and other offering costs payable by us of $28.4 million. J.P. Morgan Securities LLC, TD Securities (USA) LLC, Cantor Fitzgerald & Co. and Wells Fargo Securities, LLC acted as joint book-running managers for the IPO.

The net proceeds from our IPO have been invested according to our approved investment policy in a mix of money market funds and high-quality, fixed income securities. Our planned use of the net proceeds from the IPO as described in our final prospectus filed with the SEC pursuant to Rule 424(b)(4) under the Securities Act of 1933, as amended (the “Securities Act”) on October 25, 2024 has changed due to the discontinuation of the development of our prior lead product candidate, SEP-786. As a result, we currently expect to use our cash, cash equivalents and marketable securities, which include the net proceeds from the IPO, to advance a next-generation oral small molecule PTH1R agonist from our PTH1R program into clinical development, advance SEP-631 into clinical development, continue to advance the other programs in our pipeline, and the remainder to fund working capital and other general corporate purposes. Except for the reallocation of SEP-786 funds discussed above, there has been no material changes in the planned use of proceeds from our IPO as described in our final prospectus filed with the SEC pursuant to Rule 424(b)(4) under the Securities Act on October 25, 2024.

Issuer Repurchases of Equity Securities

None.

Item 3. Defaults Upon Senior Securities.

Not applicable.

Item 4. Mine Safety Disclosures.

Not applicable.

Item 5. Other Information.

(c) Rule 10b5-1 Trading Plans

None of our directors or officers (as defined in Rule 16a-1(f) of the Exchange Act) adopted or terminated a Rule 10b5-1 trading plan or arrangement or a non-Rule 10b5-1 trading plan or arrangement, as defined in Item 408(c) of Regulation S-K, during the fiscal quarter ended March 31, 2025 covered by this Quarterly Report.

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Item 6. Exhibits.

(a) Exhibits.

		Incorporated by Reference
Exhibit Number	Description	Form	File No.	Exhibit	Filing Date
3.1	Amended and Restated Certificate of Incorporation of the Registrant.	8-K	001-42382	3.1	October 28, 2024
3.2	Amended and Restated Bylaws of the Registrant.	8-K	001-42382	3.2	October 28, 2024
4.1†	Amended and Restated Investors’ Rights Agreement, by and among the Registrant and certain of its stockholders, dated as of June 28, 2023.	S-1	333-282469	4.1	October 24, 2024
4.2	Specimen Common Stock Certificate.	S-1	333-282469	4.2	October 24, 2024
31.1*	Certification of Principal Executive Officer Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.
31.2*	Certification of Principal Financial Officer Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.
32.1*+	Certifications of Principal Executive Officer and Principal Financial Officer Pursuant to 18 U.S.C. Section 1350, as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.
101.INS*	Inline XBRL Instance Document – the instance document does not appear in the Interactive Data File because XBRL tags are embedded within the Inline XBRL document.
101.SCH*	Inline XBRL Taxonomy Extension Schema With Embedded Linkbase Documents
104*	Cover Page formatted as Inline XBRL and contained in Exhibit 101

* Filed herewith.

+ The certifications furnished in Exhibit 32.1 hereto are deemed to be furnished with this Quarterly Report and will not be deemed to be “filed” for purposes of Section 18 of the Exchange Act, except to the extent that the Registrant specifically incorporates it by reference.

† Annexes, schedules and/or exhibits have been omitted pursuant to Item 601(a)(5) of Regulation S-K. The Registrant agrees to furnish supplementally a copy of any omitted attachment to the SEC on a confidential basis upon request.

(b) Financial Statement Schedules.

None.

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SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this Quarterly Report to be signed on its behalf by the undersigned, thereunto duly authorized.

	Septerna, Inc.
Date: May 15, 2025	By:	/s/ Jeffrey Finer, M.D., Ph.D.
		Jeffrey Finer, M.D., Ph.D.
		President and Chief Executive Officer
		(Principal Executive Officer)
Date: May 15, 2025	By:	/s/ Gil M. Labrucherie, CFA, J.D.
		Gil M. Labrucherie, CFA, J.D.
		Chief Financial Officer
		(Principal Financial Officer and Principal Accounting Officer)

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