EX-99.1 2 d94932dex991.htm EX-99.1 EX-99.1

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 Ascendis Pharma A/S 39th Annual J.P. Morgan Healthcare Conference January 11, 2021 All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation. Exhibit 99.1


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Cautionary Note On Forward-Looking Statements This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, such as statements regarding our future results of operations and financial position, including our business strategy, prospective products, availability of funding, clinical trial results, product approvals and regulatory pathways, collaborations, licensing or other arrangements, the scope, progress, results and costs of developing our product candidates or any other future product candidates, the potential market size and size of the potential patient populations for our product candidates, timing and likelihood of success, plans and objectives of management for future operations, the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates, future results of current and anticipated products, and the future operations of VISEN Pharmaceuticals are forward-looking statements. These forward-looking statements are based on our current expectations and beliefs, as well as assumptions concerning future events. These statements involve known and unknown risks, uncertainties and other factors that could cause our actual results to differ materially from the results discussed in the forward-looking statements. These risks, uncertainties and other factors are more fully described in our reports filed with or submitted to the Securities and Exchange Commission, including, without limitation, our most recent Annual Report on Form 20-F filed with the SEC on April 3, 2020 particularly in the sections titled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations”. In light of the significant uncertainties in our forward-looking statements, you should not place undue reliance on these statements or regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified timeframe, or at all. Any forward-looking statement made by us in this presentation speaks only as of the date of this presentation and represents our estimates and assumptions only as of the date of this presentation. Except as required by law, we assume no obligation to update these statements publicly, whether as a result of new information, future events, changed circumstances or otherwise after the date of this presentation. This presentation concerns product candidates that are or have been under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration, European Medicines Agency or other foreign regulatory authorities. These product candidates are currently limited by U.S. Federal law to investigational use, and no representations are made as to their safety or effectiveness for the purposes for which they are being investigated. Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo and TransCon are trademarks owned by the Ascendis Pharma Group. © January 2021 Ascendis Pharma A/S.


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Company Overview Create best-in-class products addressing unmet medical needs by applying TransCon™ technologies to parent drugs with clinical proof-of-concept or clinically validated pathways Endocrinology rare disease TransCon hGH: Pediatric growth hormone deficiency (GHD): BLA and MAA submitted, phase 3 trials in China1 ongoing and Japan initiated Adult GHD: Global phase 3 foresiGHt Trial ongoing TransCon PTH: Adult hypoparathyroidism (HP) phase 3 PaTHway Trial in North America and Europe ongoing TransCon CNP: Achondroplasia phase 2 trials: ACcomplisH Trial ongoing and ACcomplisH China Trial1 initiated Oncology TransCon TLR7/8 Agonist: IND filed TransCon IL-2 b/g: IND filing or similar expected in Q3 2021 As of September 30, 2020, cash, cash equivalents and marketable securities of €957.5 million 1 Conducted by VISEN Pharmaceuticals. BLA = Biologics License Application. MAA = Marketing Authorisation Application.


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Vision 3x3: Building a Leading BioPharma Company Our Goal is to Achieve Sustainable Growth through Multiple Approaches Obtain regulatory approval for three independent Endocrinology Rare Disease products TransCon hGH for pediatric growth hormone deficiency TransCon PTH for adult hypoparathyroidism TransCon CNP for achondroplasia Grow Endocrinology Rare Disease pipeline through Global clinical reach Pursuing 9 total indications, label optimization, and life cycle management New endocrinology products Establish global commercial presence for our Endocrinology Rare Disease area Build integrated commercial organization in North America and select European countries Establish global commercial presence through partners with local expertise and infrastructure Advance a high value oncology pipeline with one IND or similar filing each year Create a third independent therapeutic area with a diversified pipeline


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Diverse Pipeline of Independent Product Candidates 1Excludes rights granted to VISEN Pharmaceuticals in Greater China. 2In phase 3 development for pediatric growth hormone deficiency in Greater China through strategic investment in VISEN Pharmaceuticals. 3US PDUFA June 25, 2021.


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Endocrinology Rare Disease All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.


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TransCon hGH: Once-Weekly Replacement Therapy All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.


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Growth Hormone Supports Overall Endocrine Health 1de Boer, H. et al. J. Clin. Endocrinol. Metab. 1997; 82(7): 2032-2036. 2Rutherford, O. M. et al. Clin. Endocrinol 1991; 34(6): 469-475. 3Colle, M., J. Auzerie. Horm. Res. 1993; 39(5-6): 192-196. 4Johannsson, G., et al. J. Clin. Endocrinol. Metab. 1999; 84(12): 4516-4524. 5Stabler, B. et al. Horm. Res. 1996; 45(1-2) 30-33 6Leonga, G., Johannsson, G. Horm. Res. 2003; 60(suppl1): 78-85 7Colao, A. et al. J. Clin. Endocrinol. Metab. 2002; 87(8): 3650-3655. 8Bex, M., Bouillon, R. Horm. Res. 2003; 60(suppl3): 80-86. Fractures8 Ultimate Height Achievement1 Cardiovascular Disease6,7 Mental Health5 Body Composition2,3,4 Daily hGH addresses all the symptoms of the disease; long-acting growth hormone products must retain the properties of hGH to adequately address the totality of the disease


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Pediatric GHD Patients Continue Approaching Normal Height Children initially treated with TransCon hGH maintained an advantage in height SDS improvement Height SDS Change from Baseline (LS Mean + SE) TransCon hGH Genotropin Genotropin switch to TransCon hGH heiGHt Trial subjects rolled over into enliGHten Trial (long-term extension) *Denotes treatment difference resulted in a nominal P value < 0.05. Maniatis A et al. Oral presentation at ENDO 2020 and Data on file.


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Key Learnings from TransCon hGH Pediatric Clinical Trials TransCon hGH demonstrated a safety profile comparable to that of a daily hGH1  TransCon hGH demonstrated superior AHV2 compared to a daily hGH with a PK profile2 of released hGH that may lead to more efficient utilization by target tissues Data suggest hGH released from TransCon hGH maintains the same mode of action as daily hGH and preserves the biological balance between hGH and IGF-1 effects1,2,3,4  TransCon hGH and a daily hGH demonstrated similar relationship between change in height SDS and change in average IGF-1 SDS3,4,5 TransCon hGH showed predictable linear IGF-1 response to dose titrations5 TransCon hGH demonstrated consistent safety and efficacy profile following switch from daily hGH in both fliGHt and enliGHten trials1 1Maniatis A et al. Oral presentation at ENDO 2020. 2Thornton P, et al. Oral presentation at ENDO 2019. 3Chatelain P, et.al. J Clin Endocrinol Metab 2017, 102(5): 1673 – 1682. 4Vlachopapadopoulou et al. Oral presentation at ESPE 2019. 5Data on file.


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Impact of Growth Hormone Distribution ADIPOSE TISSUE hGH directly stimulates the breakdown of fat1 BONE Optimal growth achieved via direct stimulation of GH receptors in bone and through IGF-11 TransCon hGH is designed to release hGH to achieve the same tissue distribution and receptor activation in the body as daily hGH, with once-weekly administration 1Kaplan SA, Cohen P. J Clin Endocrinol Metab. 2007;92(12):4529-4535. 


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Adult GHD Global Phase 3 ForesiGHt Trial Design Primary Objective: Demonstrate efficacy compared to placebo Endpoints Primary: Change from baseline in trunk % fat at 38 weeks Secondary: Change from baseline in trunk fat mass (kg) and total body lean mass (kg) at 38 weeks Exploratory: Total body fat mass, trunk lean mass, visceral adipose tissue, total body bone mineral content and density, TRIM-AGHD, PGIS, and EQ-5D-5L scores Safety: AEs, labs, vital signs, anti-drug antibodies, ECGs, fundoscopy PK/PD: hGH, lonapegsomatropin, mPEG, IGF-1, IGFBP-3 Key Eligibility Criteria for Main Period Enrollment (All Regions) Adults and older adults with AGHD Ages 23 – 75 years GH treatment-naïve or no GH therapy in past 12 months IGF-1 SDS ≤ -1.0 at screening Global: Europe, North America, Asia (including Japan and China*) ~ 80 Once-weekly TransCon hGH Once-weekly TransCon hGH ~ 80 Once-weekly Placebo Once-weekly Placebo ~ 80 Daily hGH Daily hGH Dose titration (12 weeks) Target maintenance dose (26 weeks) Once-weekly TransCon hGH Once-weekly TransCon hGH Once-weekly TransCon hGH Open-Label Extension period (52 weeks) Primary comparison for main period (double-blind for main period) Open label Main period (38 weeks): 1:1:1 randomization Once-weekly TransCon hGH Japan only: Patients previously treated with commercially available daily hGH All regions *Conducted by VISEN Pharmaceuticals.


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TransCon hGH: New Paradigm for Growth Hormone Treatment *Conducted by VISEN Pharmaceuticals. In the phase 3 heiGHt Trial, TransCon hGH demonstrated superior AHV (P = 0.009) with a comparable safety and tolerability profile compared to a daily hGH1 In pediatric GHD, submitted BLA June 2020 and MAA September 2020 (including Auto-Injector): FDA mid-cycle call held in December 2020, no advisory committee expected, PDUFA June 25, 2021 EMA MAA process and review underway, day 120 questions expected end of January Received orphan designation in United States and Europe for GHD  PIP approved for children from 6 months to less than 18 years Global reach and label expansion: China: Pediatric GHD phase 3 ongoing*  Japan: Pediatric GHD phase 3 riGHt Trial, Clinical Trial Notification (CTN) filed Q3 2020 Adult GHD: Ongoing global phase 3 foresiGHt Trial, complete enrollment expected by late 2021 or early 2022 Commercial manufacturing ongoing Multiple independent patent filings to provide potential IP protection into 2039 1Thornton P, et al. Oral presentation at ENDO 2019.


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TransCon PTH: PTH Replacement Therapy for Hypoparathyroidism All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.


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Hypoparathyroidism 1 Nat Rev Dis Primers 2017 Aug 31;3:17055 2Ascendis Pharma HP Patient Experience Research. 3Endo Pract. 2014, 20(7);671-679. 4 J Bone Miner Res 2013, 28: 2570-2576; 5J Clin Endocrinol Metab 2012, 97(12): 4507-4514.  6J Bone Miner Res 2013, 28: 2277-2285. Hypocalcemia Paresthesias, muscle cramps, tetany, laryngospasm, seizures, coma 85%  Report inability to perform household activities Brain fog 76%  Either unable to work or report significant interference with work due to HP symptoms Anxiety due to “fear of crash” Hypercalcemia Nocturia, polyuria, constipation, muscle weakness, coma Short-term Symptoms1 Long-term Complications4-6 4-fold       Increased risk of renal disease (nephrocalcinosis, nephrosclerosis, kidney stones & renal insufficiency) 2-fold   Increased risk of depression or bipolar  disorder 4-fold  Increased risk of seizures 79%  Require hospitalizations or emergency department visits Patient Burden2,3


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~86k – 223k 2013, Underbjerg et. al., Cardiovascular and Renal Complications to Postsurgical Hypoparathyroidism: A Danish Nationwide Controlled Historic Follow-up Study 2015, The Epidemiology of Nonsurgical Hypoparathyroidism in Denmark: A Nationwide Case Finding Study 2016, Astor et. al., Epidemiology and Health-Related Quality of Life in Hypoparathyroidism in Norway Europe Chronic Hypoparathyroidism: Significant Patient Population ~70k – 112k 2013, Powers et. al., Prevalence and Incidence of Hypoparathyroidism in the United States Using a Large Claims Database, JBMR 2011, Clarke et. al., Co-morbid Medical Conditions Associated with Prevalent Hypoparathyroidism: A Population-Based Study Estimated Prevalence: ~200k in these 4 regions USA ~12k – 13k S. Korean ICD-10 codes Ascendis market research South Korea ~25k – 32k 2017. Shishiba et. al., Prevalence of postsurgical hypoparathyroidism in Japan: Estimated from the data of multiple institutes 1999. Nakamura et. al., Prevalence of Idiopathic Hypoparathyroidism and Pseudohypoparathyroidism in Japan Ascendis market research Japan


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TransCon PTH Phase 2 Trial Design PRO = Patient-reported Outcome. HPES = Hypoparathyroidism Patient Experience Scale. BMD = Bone Mineral Density. TBS =Trabecular Bone Score. DXA = Dual-Energy X-Ray Absorptiometry. FECa = Fractional Excretion of Calcium. 59 adult subjects with HP currently receiving standard of care (active vitamin D + calcium); 1:1:1:1 randomization Primary Composite Endpoint (4 weeks) Proportion of subjects with: Normal serum calcium; and Normal FECa (or at least 50% decrease from baseline); and Off active vitamin D; and Taking ≤ 1,000 mg/day calcium Double-Blinded Treatment (4 weeks) RANDOMIZATION Screening ≤ 4 weeks Open-Label Extension (OLE) TransCon PTH Individual Dosing (6 – 30 µg/day) TransCon PTH Titration & SoC Optimization Individualized Dosing TransCon PTH 15 µg/day TransCon PTH 18 µg/day TransCon PTH 21 µg/day Placebo Key Secondary Endpoints (4 weeks) Primary composite and taking ≤ 500 mg/day calcium Additional Endpoints ≥ 4 weeks PRO measures (including HPES and SF-36) Nephrolithiasis, nephrocalcinosis, vascular calcification, ER/urgent care visits and hospitalizations BMD and TBS by DXA, bone turnover markers, 24-hour urine calcium excretion (in extension only) ALL SUBJECTS


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Preliminary PaTH Forward OLE Safety Summary TransCon PTH was generally well-tolerated 58 out of 59 randomized subjects currently receiving TransCon PTH in OLE* No drug-related serious TEAEs were reported No TEAEs leading to discontinuation of study drug TEAEs with TransCon PTH reflect known PTH pharmacology Injections were well-tolerated using pen injector planned for commercial presentation No new safety signals identified in the OLE portion of the study *As of January 5, 2021. Preliminary PaTH Forward OLE 6-month data. TEAE = Treatment emergent adverse event No subjects had PTH TEAEs related to hyper- or hypocalcemia leading to ER/urgent care visit and/or hospitalization


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OLE starts PaTH Forward OLE Mean Active Vitamin D Dose TransCon PTH enabled discontinuation of active vitamin D within two weeks of treatment initiation Preliminary PaTH Forward OLE 6-month data. Data on file. Mean Active Vitamin D Dose µg/day (± SE) Weeks


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OLE starts PaTH Forward OLE Mean Calcium Supplement Dose TransCon PTH enabled rapid and continuous calcium supplement reduction over 6-month study period Preliminary PaTH Forward OLE 6-month data. Data on file. Mean Calcium Dose mg/day (± SE) Weeks


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Mean Calcium Corrected for Albumin mg/dL (± SE) PaTH Forward OLE Mean Serum Calcium and Mean 24-Hour Urine Calcium Preliminary PaTH Forward OLE 6-month data. Data on file. ULN = Upper limit of normal. Mean 24-hour Urine Calcium mg/24hr ULN (men) ULN (women) Mean 24-hour urine calcium normalized while maintaining normal mean serum calcium Mean Serum Calcium Mean 24-hour Urine Calcium Normal range Weeks (N = 36) (N = 8) (N = 44)


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PaTH Forward OLE Change in SF-36® Health Survey Domain Mean Scores (SD) Preliminary PaTH Forward OLE 6-month data. Data on file. Green: Means above lower limit of population norm (47). (SD). *PF (physical functioning), RP (role physical), BP (bodily pain), GH (general health), VT (vitality), SF (social functioning), RE (role emotional), MH (mental health), PCS (physical component summary), MCS (mental component summary).    Placebo (N = 15) Placebo Switch to TransCon PTH (N = 15)  TransCon PTH (N = 44)  All TransCon PTH (N = 59) SF-36 Domain* Baseline Week 4 6 Months Baseline Week 4 6 Months Baseline 6 Months PF 45 (11) 46 (14) 51 (7) 46 (9) 51 (6) 52 (5) 46 (10) 51 (6) RP 42 (10) 42 (14) 49 (11) 42 (10) 49 (8) 51 (6) 42 (10) 50 (7) BP 43 (11) 40 (16) 46 (10) 46 (10) 49 (8) 51 (9) 45 (10) 50 (9) GH 44 (10) 47 (11) 50 (7) 43 (10) 47 (8) 51 (9) 43 (10) 51 (8) VT 44 (12) 43 (12) 52 (10) 42 (11) 49 (9) 53 (8) 43 (11) 53 (8) SF 44 (11) 41 (15) 53 (5) 42 (10) 50 (8) 52 (6) 43 (10) 52 (6) RE 45 (12) 39 (16) 51 (7) 42 (13) 49 (10) 50 (8) 43 (13) 50 (7) MH 47 (9) 47 (11) 55 (5) 46 (9) 51 (8) 51 (8) 46 (9) 52 (7) PCS 43 (12) 44 (14) 48 (8) 45 (10) 49 (7) 51 (7) 44 (11) 50 (8) MCS 46 (10) 43 (12) 54 (6) 43 (11) 50 (9) 51 (8) 44 (11) 52 (8)


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OLE starts OLE starts PaTH Forward OLE % Change in Mean P1NP and CTx Preliminary PaTH Forward OLE 6-month data. Data on file. At 26-week point, observed lower level of increase for anabolic compared to catabolic bone turnover % Change Procollagen 1N-Terminal Propeptide (± SE) % Change in Mean P1NP % Change in Mean CTx % Change Type I Collagen C-Telopeptide (± SE) Weeks Weeks


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Bone Mineral Density by DXA *A Z-score compares bone density to the average values for a person of the same age and gender.  Preliminary PaTH Forward OLE 6-month data. Data on file. With TransCon PTH treatment, BMD mean Z-score trended toward normalization at week 26 At baseline, mean BMD Z-scores* at lumbar spine, femoral neck and total hip were elevated due to reduced bone turnover  N = 44 Baseline Week 26 Week 26 Change from Baseline Lumbar Spine L1-L4       Mean BMD Z-score 1.6 0.9 -0.7 Femoral Neck        Mean BMD Z-score 1.2 0.7 -0.5 Total Hip        Mean BMD Z-score 1.0 0.6 -0.5 1/3 Radius         Mean BMD Z-score 0.4 0.4 0.0


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PaTHway Phase 3 Trial Design 1 Enrollment increased to 76 subjects to ensure evaluable data for 68. 2 If needed to meet recommended dietary intake of calcium, it is permitted to take calcium supplements ≤ 600 mg/day as a nutritional supplement. Double-blind, placebo-controlled trial with an open-label extension period 761 adults with chronic hypoparathyroidism randomized 3:1 (TransCon PTH:placebo) Primary Objective Confirm treatment effect of TransCon PTH in adults with hypoparathyroidism Key Eligibility Criteria Adults with chronic hypoparathyroidism (i.e., for at least 26 weeks) Age ≥ 18 years Reliant on calcitriol ≥ 0.50 mcg per day or alfacalcidol ≥ 1.0 mcg per day, and therapeutic elemental calcium ≥ 800 mg/day Serum calcium in normal (or just below normal) range: 7.8 – 10.6 mg/dL (1.96 – 2.64 mmol/L) No PTH or PTHrP therapy within 4 weeks prior to Screening Countries Planned Europe (Germany, United Kingdom, Denmark, Norway, France, Italy, Hungary) North America (United States, Canada) Primary Composite Endpoint at Week 26 Proportion of subjects with: Serum calcium in the normal range (8.3 – 10.6 mg/dL) and Independence from active vitamin D and Independence from calcium supplements2 Selected Secondary Endpoints at Week 26 24-hour urine calcium excretion Serum phosphate levels Hypoparathyroidism Patient Experience Scale measures 36-Item Short Form Survey (SF-36) measure ~ 57 TransCon PTH Subjects ~ 19 Placebo Subjects TransCon PTH TransCon PTH Open-Label Extension period (156 weeks) Double-Blind Main period (26 weeks) Week 26


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TransCon PTH: A Potential PTH Replacement Therapy Phase 1 and phase 2* data support profile of TransCon PTH as a potential PTH replacement therapy for HP Preliminary phase 2 PaTH Forward OLE results at month 6*: 86% of subjects had (1) normal serum calcium, (2) off active vitamin D and (3) taking ≤ 600 mg/day of calcium Mean scores for all summary and subdomains of SF-36 were normal for all TransCon PTH subjects at 6 months in PaTH Forward OLE 58 out of 59 randomized subjects currently receiving TransCon PTH in OLE** 12-month OLE update anticipated in Q2 2021 Received orphan designation in US and EU Expect to file CTN for Japanese adult HP phase 3 study in Q2 2021 North American and European phase 3 PaTHway Trial results expected Q4 2021 *Preliminary PaTH Forward OLE 6-month data. Data on file. **As of January 5, 2021.


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TransCon CNP: The New Frontier of Growth Biology All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.


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TransCon CNP - Two Randomized Placebo-Controlled Trials ACcomplisH Trial Sequential rising dose (6, 20, 50, 100 µg/kg) study in cohorts of 12 – 15 subjects, double-blind, randomized 3:1 (TransCon CNP to placebo) Higher dose cohorts initiated following blinded DMC review of prior dose 3-month interim data 12-month blinded follow-up with roll over to long-term extension trial ACcomplisH China Trial* Designed for dose expansion at effective dose determined from ACcomplisH Trial, double-blind, randomized 3:1 (TransCon CNP to placebo) Plan to enroll over 60 subjects After 12-month blinded period, subjects roll over to long-term extension trial TransCon CNP clinical program update expected Q4 2021 *Conducted by VISEN Pharmaceuticals.


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Oncology All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.


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TransCon Positioned to Transform Cancer Therapy TransCon systemic and intratumoral technologies designed to enhance anti-tumor effects by Providing sustained modulation of tumor microenvironments Activating cytotoxic immune cells Tumor cells Immune-suppressing cells Cytotoxic T cells and other cancer fighters Cold Tumor Hot Tumor No Tumor X Applicable for diverse drug classes and mechanisms of action; opportunity for combination approaches


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Parent drug is transiently bound to TransCon linker-hydrogel carrier, which inactivates, shields parent drug and prevents clearance Designed to provide sustained high local drug levels with low systemic exposure; hydrogel degrades into small polymers that are renally cleared Following injection, the linker is designed to autocleave at a specific rate to predictably release unmodified parent drug TransCon Technology: Sustained Localized Release Linker cleavage dependent on pH and temperature Parent drug (inactive) Unmodified parent drug (active) TransCon hydrogel carrier Receptor Renal clearance TransCon linker Prodrug (inactive)


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TransCon IT: Potential Paradigm Shift in Intratumoral Delivery TransCon Intratumoral (IT) addresses the problems of conventional IT administration including rapid clearance from the tumor, high systemic exposure and toxicity Data on file. TransCon IT is designed to stay in the tumor and slowly release the drug ensuring high tumor drug concentration and low systemic exposure Systemic concentration of released drug Tumor concentration of released drug Single TransCon IT Dose in Mice Concentration (ng/mL ± SD)


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Two Near-term Clinical Candidates – Potential to Address All Steps of the Immunity Cycle Combination approaches enable impact on all critical steps of anti-tumor response TransCon TLR7/8 Agonist for IT delivery and enhanced tumor-antigen presentation TransCon TLR7/8 Agonist TransCon IL-2 b/g TransCon IL-2 b/g TransCon TLR7/8 Agonist Designed to enhance antigen presentation and, thereby, promote activation of cytotoxic immune cells (IND filed) TransCon IL-2 b/g for systemic activation of tumor-antigen specific cytotoxic cells Designed to aid T cell and NK cell expansion and infiltration of immune cells into tumors (IND or similar planned for Q3 2021) Additional TransCon Candidates One IND or similar filing each year for new TransCon candidates with the potential to affect all steps in the immunity cycle


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TransCon TLR7/8 Agonist TransCon TLR7/8 Agonist All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.


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Efficacy Each injection designed to provide sustained exposure in the tumor for months to enhance immune activation Reduce risk of reaching super-high “ablative”, non-immunogenic levels Safety Low systemic toxicity expected to reduce dose-limiting adverse events Infrequent dosing designed to improve practicality and reduce injection-related complications Broad application Essentially all solid tumors are accessible for injection Opportunity for TransCon TLR7/8 Agonist in Solid Tumors Designed for IT, sustained release with minimal systemic exposure aiming for superior efficacy TransCon TLR7/8 Agonist


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Phase 1/2 Dose Escalation and Dose Expansion Study of TransCon TLR7/8 Agonist Alone or in Combination with CPI MTD = Maximum Tolerated Dose; ORR = Overall Response Rate using RECIST 1.1. Dose Escalation (“3 + 3” Design) Dose Expansion Part 1: Monotherapy Any solid tumor, any line Part 2: Combination with CPI Indications with known CPI activity Part 3: Combination with CPI Multiple indication-specific cohorts at Recommended Ph2 Dose (RP2D) Objectives: Safety and tolerability; define MTD and RP2D Pharmacokinetics / pharmacodynamics (PK/PD) Preliminary anti-tumor efficacy (ORR, duration of and time to response)


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Initial Indication Selection Based on Strong Scientific Rationale to Focus on HPV-associated Cancers HPV-associated: HNSSC, anal, vulvar, penile, vaginal and cervical cancer Melanoma Merkel cell carcinoma Squamous cell carcinoma Gastric cancer Esophageal cancer Hepatocellular carcinoma Non-small cell lung cancer MSI-H/dMMR solid tumors (CRC, endometrial, etc.) TMB-H solid tumors Triple-negative breast cancer Renal cell carcinoma Urothelial carcinoma


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TransCon TLR7/8 Agonist: Aiming to Transform How Cancer is Treated TransCon technology offers a new treatment paradigm for IT sustained delivery with potential for superior efficacy and safety Single IT dose provides exposure for weeks/months Low systemic exposure, well tolerated in mice and non-human primates (NHP) Complete tumor regressions, including abscopal effects and immunological memory against re-challenge observed in mouse tumor models Sustained IT release expected to enable superior efficacy IND filed December 2020 Focus on HPV-associated tumors as first indications Initiation of CPI combo dose escalation expected Q2 2021 Initial results for monotherapy dose escalation expected Q4 2021


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TransCon IL-2 b/g TransCon IL-2 b/g All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.


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TransCon IL-2 b/g: Optimized b/g Bias, Potency and PK *Data on file. 1Potency determined in HH cell-based assay expressing IL-2R b/g. 2NHP Study Dose: 0.1 mg/kg. T1/2 ~32 h2 Variant b/g Bias Potency Reduction1 IL-2 No n/a IL-2 b/g 5 kDa Yes ~4-fold IL-2 b/g 10 kDa Yes ~6-fold IL-2 b/g 30 kDa Yes ~20-fold Optimizing IL-2 b/g bias and potency through permanent PEGylation TransCon technology provides low Cmax and prolonged exposure Independently optimized receptor bias and potency as well as pharmacokinetics, to create a potentially best-in-class IL-2 product Free IL-2 b/g (ng/mL)


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Robust Increase in Absolute Lymphocyte Count with Minimal Eosinophil Expansion in NHP Q3W = every 3 weeks. 1Data on file. 2Rosen D, et al. AACR annual meeting. 2020; Poster 4507. 3Rand, et al. J Clin Invest. 1991; 88: 825. 4Van Haelst Pisani C, et al. Blood. 1991;78:1538. Single dose supporting Q3W dosing; minimal effect on eosinophils, minimal IL-5 and IL-6 levels suggests low risk of vascular leak syndrome syndrome3,4 Mean ~27-fold increase in Absolute Lymphocyte Count Minimal impact on eosinophils No capillary leak syndrome observed up to 0.9 mg/kg In vivo proliferation responses remain dose dependent up to 0.3 mg/kg TransCon IL-2 b/g1 (Single Dose on Day 1) Absolute Lymphocyte Count/μL Eosinophil Count/μL IL-5 (pg/ml) IL-6 (pg/ml) Doses are indicated as mg/kg; average animal weight 3.13 kg (2.46 – 3.69 kg)


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Potent CD8⁺ T Cell and NK Cell Peripheral Expansion and Activation in NHP *Fold change using cell counts derived from hematology lymphocyte counts and flow cytometry-based frequencies within lymphocytes. Data on file. Expansion and activation of cytotoxic lymphocyte subsets observed following a single dose of TransCon IL-2 b/g CD8⁺ T cells NK cells % Ki67+ Fold Change* Mean ~17-fold expansion of CD8+ T cells Mean ~25-fold expansion of NK cells Almost 100% of cells expressing Ki67 activation marker


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TransCon IL-2 b/g Expands Ratios of CD8+ T Cells and NK Cells Over Treg Cells in NHP Data on file. Fold change of cell ratios A single dose of TransCon IL-2 b/g resulted in durable and robust increases in the ratios of CD8+ T cells and NK cells over Treg cells in NHP Mean ~5-fold increase of CD8+ T cell / Treg ratio Mean ~7-fold expansion of NK cell / Treg ratio


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Syngeneic CT26 tumor model (colon-derived tumor line) Evaluation of Immune Memory and Potential Cross-immunity Following TransCon IL-2 b/g plus TransCon TLR7/8 Agonist Re-challenge of complete responders with CT26 Challenge of complete responders with different tumor type, EMT6 (mammary-derived) Treatment with TransCon IL-2 b/g + TransCon TLR7/8 Agonist 73 days after initial treatment No additional treatment 28 days after CT26 re-challenge No additional treatment


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The immune activating mechanism of action of TransCon IL-2 b/g plus TransCon TLR7/8 Agonist and complete responses suggests potential for anti-tumor immune memory TransCon IL-2 b/g Plus TransCon TLR7/8 Agonist Resulted in Durable Complete Tumor Regressions in the CT26 Tumor Model Data on file. Buffer control TransCon IL-2 b/g (3 doses) + TransCon TLR7/8 Agonist (single dose) 6/8 Complete responses (CR)


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Protection against initial tumor and a new tumor type, suggesting potent anti-tumor memory and cross-reactive anti-tumor immunity Potent Immune Memory and Cross-Reactive Anti-Tumor Response Against a New Tumor Type Data on file. CT26 re-challenge of CRs (colon-derived tumor line) EMT6 challenge of CRs (mammary-derived tumor line) 6/6 CRs 6/6 CRs


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Potential Paradigm Shift in How Cancer is Treated Building a pipeline using TransCon technologies that may enable a new treatment paradigm building upon well-known biology Two product candidates demonstrating potentially best-in-class properties TransCon TLR7/8 Agonist designed for IT, long-term sustained release for superior efficacy with minimal systemic adverse events; IND filed TransCon IL-2 b/g designed for optimized IL-2Rb/g bias and potency, combined with low Cmax and long exposure; IND or similar planned for Q3 2021 Combination resulted in potent anti-tumor responses and immunological memory, including cross-immunity against a new tumor type Building diversified pipeline through one IND or similar filing each year for new TransCon product candidates with the potential to affect all steps in the immunity cycle


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Global Commercial Strategy – Multiple Approaches Establishing global commercial presence to deliver potential best-in-class TransCon product candidates to address patients’ unmet medical needs Laying groundwork for successful future endocrinology rare disease launches US commercial organization in place for potential launch of TransCon hGH in pediatric GHD Preparing for commercialization in Europe Building integrated organization in select countries for potential TransCon hGH MAA approval in Q4 2021 Evaluating established distribution channels in other countries Establishing global commercial presence through partners with local expertise and infrastructure Collaborating with VISEN Pharmaceuticals for Greater China Partner in Japan and South Korea when appropriate Serve patients in ROW through established sales and distribution systems


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VISEN Pharmaceuticals VISEN was formed in 2018 to develop, manufacture, and commercialize TransCon endocrinology rare disease product candidates in Greater China, the second largest pharmaceutical market VISEN responsible for development, manufacturing and commercialization in Greater China Supports integration of Ascendis global clinical development and commercialization strategies In Series A financing, Vivo and Sofinnova invested $40 million, and Ascendis contributed rights to TransCon hGH, TransCon PTH and TransCon CNP for 50% equity ownership VISEN closed Series B equity financing on January 8, 2021 Raised a total of $150 million from new and existing investors; Ascendis participated with a $12.5 million investment Ascendis now owns ~44% of issued and outstanding shares Following closing of the Series B financing, Ascendis has an additional board seat: Michael Wolff Jensen, Chairman, Senior Vice President and Chief Legal Officer of Ascendis, became a member of VISEN’s board and serves as Chairman Jan Mikkelsen, CEO of Ascendis will continue to serve on the VISEN board


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FDA approval of BLA Selected 2021 Expected Key Milestones 50 Q1 2021 Q2 2021 Q3 2021 Q4 2021 Clinical program update Initiate CPI combo dose escalation EC approval of MAA Submit IND or similar Top-line phase 3 results (North America and EU) adult HP File CTN for Japanese adult HP phase 3 Initial results for monotherapy dose escalation Closed investment in VISEN TransCon hGH TransCon PTH TransCon CNP TransCon TLR7/8 Agonist US commercial launch TransCon IL-2 b/g