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6-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 6-K

 

 

REPORT OF FOREIGN PRIVATE ISSUER

PURSUANT TO SECTION 13a-16 OR 15d-16

UNDER THE SECURITIES EXCHANGE ACT OF 1934

For the month of December, 2021

Commission File Number: 001-36815

 

 

Ascendis Pharma A/S

(Exact Name of Registrant as Specified in Its Charter)

 

 

Tuborg Boulevard 12

DK-2900 Hellerup

Denmark

(Address of principal executive offices)

 

 

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.

Form 20-F  ☒                Form 40-F  ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):  ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7):  ☐

 

 

 

The presentation slides attached hereto as Exhibit 99.1 were presented in a webcast on December 14, 2021 at the Company’s virtual R&D Program Update.

The furnishing of the attached presentation is not an admission as to the materiality of any information therein. The information contained in the presentation is summary information that is intended to be considered in the context of more complete information included in the Company’s filings with the Securities and Exchange Commission (the “SEC”) and other public announcements that the Company has made and may make from time to time. The Company undertakes no duty or obligation to update or revise the information contained in this report, although it may do so from time to time as its management believes is appropriate. Any such updating may be made through the filing or furnishing of other reports or documents with the SEC or through other public disclosures.

Exhibits

 

99.1   

Virtual R&D Program Update Presentation.

SIGNATURES

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

 

    Ascendis Pharma A/S
Date: December 15, 2021     By:  

/s/ Michael Wolff Jensen

      Michael Wolff Jensen
      Senior Vice President, Chief Legal Officer
EX-99.1

Exhibit 99.1 ASCENDIS PHARMA A/S Virtual R&D Program Update December 14, 2021

Welcome & Agenda Overview Scott T. Smith Senior Vice President, Chief Financial Officer

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, expectations regarding prospective products, availability of funding, clinical trial results, product approvals and regulatory pathways, collaborations, licensing or other arrangements, the scope, support 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 SKYTROFA and 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 preliminary prospectus supplement related to the proposed public offering and our most recent Annual Report on Form 20-F filed with the SEC on March 10, 2021 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. SKYTROFA has been approved by the U.S. Food and Drug Administration for the treatment of pediatric growth hormone deficiency. SKYTROFA is and has been under clinical investigation and has not yet been approved for marketing by the European Medicines Agency or other foreign regulatory authorities. In addition, this presentation concerns other product candidates that are 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, TransCon, and All product candidates are investigational. SKYTROFA are trademarks owned by the Ascendis Pharma group. © December 2021 For investor communication only. Not for use in product promotion. 3 Ascendis Pharma A/S. Not for further distribution.

Virtual R&D Program Update Agenda 9:00-9:05 a.m. E.T. 9:55–10:35 a.m. E.T. TransCon CNP Welcome & Agenda Overview Kennett Sprogøe, Ph.D. Scott T. Smith SVP, CFO SVP, Head of Innovation and Research 9:05–9:10 a.m. E.T. Marie-Louise C. Hartoft-Nielsen, M.D., Ph.D. Opening Comments Senior Medical Director, Clinical Development Jan Møller Mikkelsen, President & CEO 10:35–11:15 a.m. E.T. 9:10–9:55 a.m. E.T. TransCon TLR7/8 Agonist TM TransCon PTH Kennett Sprogøe, Ph.D. Aimee D. Shu, M.D. SVP, Head of Innovation and Research VP, Clinical Development, Endocrine Medical Sciences Stina Singel, M.D., Ph.D. Guest Speaker Head of Clinical Development, Oncology Aliya Khan, M.D., Clinical Professor of Medicine and Director of the Calcium Disorders Clinic at 11:15–11:30 a.m. E.T. St. Joseph’s Healthcare, McMaster University Questions & Answers All product candidates are investigational. For investor communication only. Not for use in product promotion. 4 Not for further distribution.

Opening Comments Jan Møller Mikkelsen President & Chief Executive Officer

Introduction to Ascendis Pharma An expanding global footprint • Founded in 2007 in Copenhagen, Denmark Global HQ • Publicly listed on NASDAQ since 2015 Ascendis Pharma A/S Hellerup, Denmark (ASND) Research Site • TransCon™: Innovative technology US Commercial Redwood City, CA platform utilized in all product candidates Clinical Site Princeton, NJ Berlin, Germany US Office • Diverse clinical stage Endocrinology Rare Palo Alto, CA Research Site Disease and Oncology pipeline Affiliate Heidelberg, Germany VISEN Pharmaceuticals* • Our mission: Develop best-in-class Shanghai, China therapeutics addressing unmet medical needs • Our values: Patients, Science and Passion Committed to Making a Meaningful Difference in Patients’ Lives *VISEN Pharmaceuticals (known as Visen) was established in 2018 to develop and commercialize endocrinology rare disease therapies in Greater China. All product candidates are investigational. For investor communication only. Not for use in product promotion. 6 Not for further distribution.

Vision 3x3: Building a Leading Global 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. All product candidates are investigational. For investor communication only. Not for use in product promotion. 7 Not for further distribution.

Diverse Pipeline of Independent Product Candidates 7 7 8 1 Received positive CHMP opinion on November 12, 2021. Final EC decision expected within 67 days, or by end of January 2022. 2 In development in Greater China through strategic investment in VISEN Pharmaceuticals. 3 Japanese riGHt Trial. 4 Global foresiGHt Trial. 5 North American and European PaTHway Trial, Japanese PaTHway Japan Trial. 6 All product candidates are investigational. North America, Europe, and Oceania ACcomplisH Trial. 7 For investor communication only. Not for use in product promotion. transcendIT-101 Trial. 8 8 IL-beliege Trial. Not for further distribution.

TransCon PTH Clinical Update Aimee D. Shu, M.D. VP, Clinical Development, Endocrine Medical Sciences

Hypoparathyroidism: Insufficient Parathyroid Hormone • An intact PTH axis maintains normal serum calcium and phosphate – By acting on bone, kidney, and intestine – Promoting normal nerve and muscle function • Hypoparathyroidism is a two-hormone deficiency – Resulting in broad systemic dysfunction Hypoparathyroidism is the last classical hormone deficiency for which complete hormone replacement has been elusive DeLuca HF. N Engl J Med. 1973 Aug 16;289(7):359-365. Haussler MR et. al. N Engl All product candidates are investigational. J Med. 1977 Nov 3;297(18):974-983. Reichel H et. al. N Eng J Med. 1989 Apr 13; For investor communication only. Not for use in product promotion. 10 320(15):980-991. Bilezikian JP, et. al. J Bone Miner Res. 2011 Oct;26(10):2317-37. Not for further distribution.

Hypoparathyroidism: Multiple Complications Brain fog Seizures Laryngospasm & Anxiety & depression bronchospasm Infections Heart failure Renal failure Arrhythmias Abnormal skeletal Numbness & tingling dynamics Abnormal tissue Muscle spasms calcifications Fatigue Pain All product candidates are investigational. For investor communication only. Not for use in product promotion. 11 Shobak DM et. al. J Clin Endocrinol Metab. 2016 June 01;101(6):2300-2312 Not for further distribution.

Hypoparathyroidism: Acquired and Inherited Etiologies Etiologies as reported by 146 respondents to the Voices of Hypoparathyroidism survey Murphy et. al., Voices of Hypopara survey, poster presented at The Endocrine Society All product candidates are investigational. meeting, 2021. For investor communication only. Not for use in product promotion. 12 Clarke et. al. J Clin Endocrinol Metab. 2016;101(6):2284-2299. Not for further distribution.

Chronic Hypoparathyroidism: Significant Patient Population Estimated Prevalence: ~400k in these 5 regions South USA Europe Japan China Korea ~70k–112k ~86k–223k ~25k–32k ~12k–13k ~180k–220k • 2013, Powers et. al., • 2013, Underbjerg et. al., • 2017. Shishiba et. • S. Korean ICD-10 codes • 2020, Sui et. al, Time trend Prevalence and Incidence of Cardiovascular and Renal analysis of thyroid cancer al., Prevalence of postsurgical Hypoparathyroidism in the Complications to Postsurgical hypoparathyroidism in Japan: • Ascendis market research surgery in China: single United States Using a Large Hypoparathyroidism: A Danish institutional database Estimated from the data of Claims Database, JBMR Nationwide Controlled Historic analysis of 15,000 patients multiple institutes Follow-up Study • 2011, Clarke et. al., Co-morbid • 2019, Zhao et. al., Features • 1999. Nakamura et. al., Medical Conditions Associated • 2015, The Epidemiology of Prevalence of Idiopathic and trends of thyroid cancer with Prevalent Nonsurgical Hypoparathyroidism in patients with Hypoparathyroidism and Hypoparathyroidism: A in Denmark: A Nationwide Case thyroidectomies in Beijing, Pseudohypoparathyroidism in Population-Based Study Finding Study Japan China between 1994 and 2015: a retrospective study • 2016, Astor et. al., Epidemiology • Ascendis market research and Health-Related Quality of • World Bank, 2018 Life in Hypoparathyroidism in Norway • Ascendis market research All product candidates are investigational. For investor communication only. Not for use in product promotion. 13 Not for further distribution.

Conventional Therapy Targets Symptoms, Not Underlying Disease Calcitriol (active vitamin D) Calcium or its analogue alfacalcidol Endogenous production diminished Often requires high pill burden due to insufficient PTH Fails to restore normal PTH physiology and introduces secondary complications • Attempts to increase serum calcium to prevent symptoms • Fails to normalize skeletal dynamics • Fails to improve diminished quality of life • Increases filtered load of calcium—increasing the risk for developing kidney stones, nephrocalcinosis, and chronic kidney disease All product candidates are investigational. For investor communication only. Not for use in product promotion. 14 Bilezikian JP et. al. J Clin Endocrinol Metab. 2016;101(6):2313-2324 Not for further distribution.

Hypoparathyroidism: Goals of an Ideal Therapy Untreated Ideal therapy hypoparathyroidism Serum calcium ↓ normalize Serum phosphate ↑ normalize Urine calcium ↑ normalize Independence from n/a yes conventional therapy Skeletal health ↓ normalize Quality of life ↓ normalize All product candidates are investigational. For investor communication only. Not for use in product promotion. 15 Not for further distribution.

TransCon PTH Designed to Be a Hormone Replacement Therapy TransCon carrier TransCon linker Active PTH Receptor Renal clearance PTH Linker cleavage dependent (inactive) upon pH and temperature • TransCon PTH is a sustained-release prodrug designed to provide stable PTH levels in the physiological range for 24 hours/day All product candidates are investigational. Holten-Andersen L, et. al. J Bone Miner Res. 2019 Nov;34(11):2075-2086. For investor communication only. Not for use in product promotion. 16 Karpf DB, et. al. J Bone Miner Res. 2020 Aug;35(8):1430-1440 Not for further distribution.

TransCon PTH PaTH Forward (Phase 2) Trial Design Adults with hypoparathyroidism who required conventional therapy (active vitamin D + calcium) at baseline Blinded Treatment (4 weeks) TransCon PTH 15 µg/day Screening Titration of TransCon PTH and conventional therapy with the TransCon PTH 18 µg/day ≤ 4 weeks goal to maintain normocalcemia TransCon PTH 21 µg/day TransCon PTH 6–60 µg/day Placebo Week 4 Week 214 Week 58 Week 84 Primary Composite Endpoint (4 weeks) Week 58 and 84 Endpoints • Intake of active vitamin D and calcium supplements Proportion of subjects with: • Serum calcium and phosphate • Normal serum calcium; and • 24-hour urine calcium • Independence from active vitamin D; and • Adverse events • Requiring ≤ 1,000 mg/day calcium supplements; and • Bone mineral density (Week 58 only) • Patient-reported outcomes (Week 58 only) • Normal FECa (or at least 50% decrease from baseline) All product candidates are investigational. FECa, fractional excretion of calcium For investor communication only. Not for use in product promotion. 17 Khan AA, et al. J Clin Endocrinol Metab. 2021 Aug 4. Epub ahead of print Not for further distribution. RANDOMIZATION ALL SUBJECTS

PaTH Forward: Mean Serum Calcium and 24-Hour Urine Calcium Through Week 84 Mean Serum Calcium Mean 24-hour Urine Calcium 500 11 All TransCon PTH All TransCon PTH 400 Normal range Mean Mean 10 Calcium 24-hour 300 ULN (men) Corrected Urine for Albumin ULN (women) Calcium mg/dL mg/24hr (± SE) 200 (± SE) 9 100 8 0 0 8 16 24 32 40 48 56 64 72 80 88 Baseline Week 26 Week 58 Week 84 Weeks Mean 24-hour urine calcium normalized while maintaining normal mean serum calcium All product candidates are investigational. Data on file, Ascendis Pharma 2021. For investor communication only. Not for use in product promotion. 18 Not for further distribution. ULN = Upper Limit of Normal

PaTH Forward: Mean Active Vitamin D Dose Through Week 84 OLE starts 1.8 TransCon PTH 1.6 Placebo 1.4 All TransCon PTH Mean 1.2 Active 1.0 Vitamin D Dose 0.8 µg/day 0.6 (± SE) 0.4 0.2 0.0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 Weeks TransCon PTH enabled discontinuation of active vitamin D within two weeks of treatment initiation All product candidates are investigational. For investor communication only. Not for use in product promotion. 19 Data on file, Ascendis Pharma 2021. Not for further distribution.

PaTH Forward: Mean Calcium Supplement Dose Through Week 84 3,000 OLE starts TransCon PTH Placebo 2,500 All TransCon PTH 2,000 Mean Calcium 1,500 Dose mg/day 1,000 (± SE) 500 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 Weeks TransCon PTH enabled rapid and continuous calcium supplement reduction; 43 of 58 subjects were taking 0 mg, and 54 of 58 subjects were taking 0 to 600 mg at week 84 All product candidates are investigational. For investor communication only. Not for use in product promotion. 20 Data on file, Ascendis Pharma 2021. Not for further distribution.

Abnormal Skeletal Dynamics in Hypoparathyroidism Hypoparathyroid Normal 1 Representative images above show bone biopsies of the iliac crest as scanned by microcomputed tomography (microCT) Lack of PTH-driven skeletal remodeling results in abnormal bone structure 2 and may be associated with poor bone quality and increased risk of fractures All product candidates are investigational. 1. Rubin MR, et. al., Bone 2010 Jan;46(1):190-195 For investor communication only. Not for use in product promotion. 21 2. FDA presentation: Natpara Advisory Committee, September 12, 2014; Not for further distribution.

PaTH Forward: Serum Markers of Skeletal Dynamics Mean P1NP Mean CTx TransCon PTH TransCon PTH Placebo Placebo 110 1,000 All TransCon PTH OLE All TransCon PTH OLE starts starts 90 800 Procollagen Type I 70 600 1N-Terminal Collagen C- Propeptide Telopeptides ng/mL ng/L 50 400 (± SE) (± SE) 30 200 10 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 Weeks Weeks With TransCon PTH treatment, markers of anabolic and catabolic bone turnover increased above baseline, peaking in the initial weeks and trending to the mid-normal range by Week 58 All product candidates are investigational. For investor communication only. Not for use in product promotion. 22 Data on file, Ascendis Pharma 2021. Not for further distribution.

PaTH Forward: Bone Mineral Density by DXA 1 Mean Z-scores (n = 43 ) Week 58 change Region Baseline Week 26 Week 58 from baseline Lumbar spine L1-L4 1.6 1.0 0.9 ‒0.7 Femoral neck 1.0 0.5 0.4 ‒0.6 Total hip 1.0 0.6 0.5 ‒0.5 1/3 radius 0.4 0.3 0.3 ‒0.1 With TransCon PTH treatment, Week 58 mean Z-scores trended toward normalization and stabilization DXA, dual energy x-ray absorptiometry 1 includes subjects with DXA scans at both baseline and post-baseline. Two subjects missed their Week 26 scan; 2 different subjects missed their Week 58 scan. One subject had evaluable DXA scans at baseline, Week 26, and Week 58 at the hip All product candidates are investigational. region only. For investor communication only. Not for use in product promotion. 23 Data on file, Ascendis Pharma 2021. Not for further distribution.

PTH Requirements Change as Skeletal Dynamics Normalize 2.0 1.6 40 1.5 (Z-score) (mcg/day) 1.0 0.9 30 1.0 0.5 20 0.0 10 -0.5 -1.0 0 0 8 26 58 84 Study Week Mean BMD Z-score (lumbar spine) Mean TransCon PTH Dose • Over time, rates of bone • In hypoparathyroidism, • With physiologic PTH exposure, the turnover normalize skeleton mobilizes excess calcium as rates of bone turnover bone turnover increases are lower than normal, • Higher PTH exposure may resulting in above- now be required to enhance average BMD calcium-promoting activities from intestine, kidney, and bone All product candidates are investigational. For investor communication only. Not for use in product promotion. 24 BMD, bone mineral density Not for further distribution.

PaTH Forward: Treatment-Emergent Adverse Events Through Week 84 Week 84 All TransCon PTH (N =59) Subjects With – n (%) Treatment-Emergent Adverse Events (TEAE) 51 (86) Serious TEAE 5 (8) Severity Severe TEAE 3 (5) Moderate TEAE 17 (29) Mild TEAE 31 (53) Related TEAE* 22 (37) Related Serious TEAE 0 TEAE Related to Hyper- or Hypocalcemia Leading to ER/Urgent Care Visit and/or 0 Hospitalization TEAE Leading to Discontinuation of Study Drug 0 TEAE Leading to Discontinuation of Trial 0 TEAE Leading to Death 0 PaTH Forward week 84 top-line data. Percentages are calculated based on the number of subjects in the Safety Population. In the severity categories, subjects are displayed for the highest severity only. An AE is considered a TEAE if it occurred after the first dose of TransCon PTH. *Headache, hypocalcemia, nausea, dizziness, All product candidates are investigational. paresthesia, hypercalcemia and asthenia occurred in two or more subjects. For investor communication only. Not for use in product promotion. 25 Data on file, Ascendis Pharma 2021. Not for further distribution.

Summary: PaTH Forward Trial Results Through Week 84 1 • 58/59 subjects remain in the trial beyond Week 84 • At Week 84, 93% of subjects were independent from active vitamin D and therapeutic doses of calcium • Mean serum and urine biochemistries continued to be in the normal range • Through Week 58, markers of skeletal health (bone density and markers of bone turnover) continued to trend toward normalization • Symptoms, impact, and health-related quality of life continued to be improved from baseline • The majority of adverse events have been mild and unrelated • No urgent/emergent visits or hospitalizations related to hypo- or hypercalcemia All product candidates are investigational. For investor communication only. Not for use in product promotion. 26 1. And as of December 13, 2021. Not for further distribution.

TransCon PTH PaTHway (Phase 3) Trial Design Double-blind, placebo-controlled trial with an open-label extension period 1 82 adults with chronic hypoparathyroidism randomized 3:1 (TransCon PTH:placebo) Double-Blind Main period (26 weeks) Open-Label Extension period (156 weeks) Week 26 ¾ TransCon PTH 18 mcg/day TransCon PTH (titrated according to algorithm) TransCon PTH ¼ Placebo Placebo TransCon PTH Primary Composite Endpoint at Week 26 Primary Objective Confirm treatment effect of TransCon PTH in adults with hypoparathyroidism Proportion of subjects with: Key Eligibility Criteria • Serum calcium in the normal range (8.3 – 10.6 mg/dL) and • Adults with chronic hypoparathyroidism (i.e. for at least 26 weeks) • Independence from active vitamin D and • Age ≥18 years 2 • Independence from calcium supplements • Reliant on calcitriol ≥0.50 mcg per day or alfacalcidol ≥1.0 mcg per day, and Selected Other Endpoints at Week 26 therapeutic elemental calcium ≥800 mg/day • 24-hour urine calcium • Serum calcium in normal (or just below normal) range: 7.8 – 10.6 mg/dL (1.96 – 2.64 mmol/L) • Serum phosphate levels • No PTH or PTHrP therapy within 4 weeks prior to Screening • Domains from Hypoparathyroidism Patient Experience Scale measures Countries • Domains from 36-Item Short Form Survey (SF-36) measure • Europe (Germany, Denmark, Norway, Italy, Hungary) • North America (United States, Canada) 1 Sample size selected to ensure evaluable data for 68. All product candidates are investigational. 2 If needed to meet recommended dietary intake of calcium, it is permitted to take For investor communication only. Not for use in product promotion. 27 calcium supplements ≤600 mg/day as a nutritional supplement. Not for further distribution.

PaTHway Phase 3 Trial: Baseline Characteristics Characteristics Total Randomized (N=82) Age, mean years 49 years Female sex, % 78% Geographic region, % North America 62% Europe 38% Postmenopausal, % 28% Duration of hypoparathyroidism, mean years 12 years Post-surgical etiology of hypoparathyroidism, % 85% Baseline characteristics of phase 3 trial are similarto those of the phase 2 trial All product candidates are investigational. For investor communication only. Not for use in product promotion. 28 Preliminary data from an ongoing trial; data snapshot 10 AUG 2021. Subject to revisions Not for further distribution.

PaTHway Trial Includes Diverse Etiologies Idiopathic Autoimmune polyglandular syndrome 1 (APS-1) Autosomal dominant hypocalcemia (ADH1) DiGeorge syndrome HDR syndrome (hypoparathyroidism, deafness, renal disease) Acquired from Neck Surgery All product candidates are investigational. For investor communication only. Not for use in product promotion. 29 Preliminary data from an ongoing trial; subject to revisions Not for further distribution.

Potential New Treatment Paradigm for Hypoparathyroidism TransCon PTH has the potential to be the first hormone replacement therapy for hypoparathyroidism addressing major unmet medical need for a large rare disease patient population Anticipated near-term milestones for global reach and indication expansion • Phase 3 PaTHway Trial (North America + EU) top-line results expected Q1 2022 • Planned NDA submission Q3 2022 • PaTHway Japan Trial top-line results expected Q3 2022 • Planned MAA submission Q4 2022 • Initiation of pediatric hypoparathyroidism program planned Q4 2022 All product candidates are investigational. For investor communication only. Not for use in product promotion. 30 Not for further distribution.

Three Patient Journeys from the PaTH Forward Trial Aliya Khan MD, FRCPC, FACP, FACE, FASBMR Clinical Professor of Medicine Director, Calcium Disorders Clinic Director, Fellowship in Metabolic Bone Disease McMaster University 31

Aliya Khan MD, FRCPC, FACP, FACE, FASBMR • Professor of Clinical Medicine at McMaster University • Director of the Calcium Disorders Clinic • Director of Fellowship in Metabolic Bone Disease at McMaster University • Graduated from the University of Ottawa Medical School with honors • Completed postgraduate training at the University of Toronto • Published over 200 scientific papers and numerous chapters and books on osteoporosis and parathyroid disease • Received numerous national and international awards • Including Queen’s Diamond Jubilee Medal for excellence • International Hypoparathyroidism Award • International Osteoporosis Foundation award for publishing excellence • Recognized by Osteoporosis Canada for outstanding contributions to research and education • Recognized as being in the top 0.1% of the world experts in hyperparathyroidism by Expertscape. 32

Disclosure •For profit • Research grants from Amgen, Ascendis, Alexion, Radius, Takeda, Ultragenyx •Not for profit • Chair, Rapid Response Committee, Osteoporosis Canada • Co-Chair, Knowledge Translation Committee, Osteoporosis Canada • Chair, International Osteonecrosis of the Jaw (ONJ) Taskforce • Scientific Advisor to International Osteoporosis Foundation • Canadian Ambassador for American Society of Bone and Mineral Research 33

Calcium Disorders Clinic at McMaster University Medical Centre • Specialized Calcium Disorders Clinic (CDC) was established at St Joseph's Healthcare in Hamilton in 2005. • CDC has serves as a Center of Excellence for the diagnosis and management of complex calcium disorders. • Tertiary referral center for patients with complex calcium disorders from across Canada • Serves as a focal point for clinical research in parathyroid disease • AK is the principal investigator for the Canadian National Hypoparathyroidism Registry – evaluating presentation, complications, and treatment approaches • AK led the development of Canadian and International Guidelines for primary hyperparathyroidism as well as hypoparathyroidism • Leader in clinical research and medical management trials of primary hyperparathyroidism (alendronate and cinacalcet) • Leader for parathyroid replacement in hypoparathyroidism (PTH(1-84), oral PTH, TransCon PTH, and calcilytics) • Medical education for medical students, residents and fellows. • AK is Director of Fellowship in Metabolic Bone Disease – the only program in Canada providing both 1-year and 2-year Fellowship programs in Metabolic Bone Disease • Previous fellows have been recipients of international awards most recently ASBMR Young Investigator Award 2021 by the ASBMR for case series on Barakat Syndrome - rare genetic disorder associated with hypoPT 34

Patient 1: History • 57-year-old male • Employment history • Automobile painter, but • Past medical history of: took early retirement • Hypertension due to complications of • Parathyroid adenoma with hypoparathyroidism subsequent total parathyroidectomy • Contractor: was able to • Thyroid nodule and return to the work force thyroidectomy—April 17,2015 after starting TransCon PTH • Hypoparathyroidism Etiology: postsurgical • Complicated by recurrent hospital admissions for hypocalcemia and hypercalcemia 35

Hypoparathyroidism Patient Experience Scale (HPES) Patient 1: Clinical Course 80 60 40 20 0 Baseline Week 58 Baseline Week 58 • Prior to trial HPES-Impact Score HPES-Symptom • Very symptomatic with significant muscle cramps and Score paresthesias daily as well as tetany Note: lower is better • Laryngospasm in June 2017 requiring hospitalization • Several admissions hypocalcemia and hypercalcemia Short Form 36, Health Questionnaire (SF-36) • Post TransCon PTH 60 40 • Symptoms have all resolved 20 0 • Returned to work – able to complete 10-12 hours Baseline Week 58 Baseline Week 58 physically demanding construction projects Mental Component Physical Summary Component • Able to participate in sports again – recently qualified for Summary golf tournament finals Note: higher is better 36

Patient 1: Laboratory Data Albumin-Adjusted Serum Calcium (mg/dL) 24-Hour Urine Calcium (mg/day) 13 3.25 1000 25 800 20 11 2.75 600 15 9 2.25 400 10 7 1.75 200 5 5 1.25 0 0 0 2 4 26 58 84 0 26 58 84 Study Duration (Weeks) Study Duration (Weeks) Serum Phosphate (mg/dL) Active Vitamin D and Calcium Supplement Intake 6 2.0 3 1500 Active Vitamin D 1.5 4 2 1000 1.0 2 1 500 0.5 0 0.0 0 0 0 2 4 26 58 84 -26 -12 0 2 4 12 26 58 84 Study Duration (Weeks) Study Duration (Weeks) 37 Study Start Phosphate sCa (mg/dL) (mg/dL) Phosphate sCa (mmol/L) (mmol/L) Active Vitamin uCa (mg/day) D (mcg/day) Calcium uCa (mmol/day) (mg/day)

Patient 2: History • 62-year-old female • Church organist and pianist • Past medical history of: • Hypertension • Goiter, total thyroidectomy- Nov 2012 • Asthma • Hypoparathyroidism Etiology: postsurgical 38

Patient 2: Clinical Course • Prior to trial • Daily feet cramps and peri-oral numbness and tingling 3-4x/week • Afraid to hold her grandchild due to muscle cramping • Post TransCon PTH • Improved energy and sleep • Able to play the organ again as the finger cramping resolved • Able to enjoy her time with her grandchildren 39

Patient 2: Laboratory Data Albumin-Adjusted Serum Calcium (mg/dL) 24-Hour Urine Calcium (mg/day) 13 3.25 1000 25 800 20 11 2.75 600 15 9 2.25 400 10 7 1.75 200 5 5 1.25 0 0 0 2 4 26 58 84 0 26 58 Study Duration (Weeks) Study Duration (Weeks) Serum Phosphate (mg/dL) Active Vitamin D and Calcium Supplement Intake 6 2.0 3 1500 Active Vitamin D 1.5 4 2 1000 1.0 2 1 500 0.5 0 0.0 0 0 0 2 4 26 58 84 -26 -12 0 2 4 12 26 58 84 Study Duration (Weeks) Study Duration (Weeks) 40 Study Start Phosphate sCa (mg/dL) (mg/dL) Phosphate sCa (mmol/L) (mmol/L) Active Vitamin uCa (mg/day) D (mcg/day) Calcium uCa (mmol/day) (mg/day)

Patient 3: History •44-year-old female •Occupation: Operating Room Nurse •Past medical history of: • Colorectal cancer • Goiter • Papillary thyroid cancer • Thyroidectomy- Jan 2016 • Myalgia •Hypoparathyroidism Etiology: postsurgical 41

Hypoparathyroidism Patient Experience Scale (HPES) Patient 3: Clinical Course 80 60 40 20 0 Baseline Week 58 Baseline Week 58 • Prior to trial HPES-Impact Score HPES-Symptom Score • Very symptomatic with overwhelming fatigue and headaches , brain fog , irritability and depression Note: lower is better • Had to resign from position as OR nurse Short Form 36, Health Questionnaire (SF-36) • Post TransCon PTH 60 • Clarity of thought , energy and sleep all dramatically 40 20 improved and feeling “fantastic” and experiencing 0 Baseline Week 58 Baseline Week 58 major increase in energy Mental Component Physical Summary Component • States the medication has given her “new life” Summary • Was able to return to her position as an OR nurse Note: higher is better 42

Discussion: Impacts on Overall Health • Through my lenses • Psychosocial aspects • Impacts on family • Pill burden and adherence to conventional therapy 43

Science and Biology of C-type Natriuretic Peptide (CNP) as a Treatment for Achondroplasia Kennett Sprogøe, Ph.D. SVP, Head of Innovation and Research

Growth Hormone Deficiency and Achondroplasia Differ at the Level of the Growth Plate Growth Hormone Deficiency Achondroplasia (ACH) Pituitary gland malfunction Constitutive hyperactive FGFR3 Cause Insufficient endogenous GH signaling caused by receptor mutation Untreated growth plate Normal organization Dysfunctional growth plate condition Inhibit hyperactive FGFR3 signaling with Treatment approach Replacement of insufficient GH continuous CNP exposure Reorganization of growth plate Initial Treatment effect Catch-up growth response leading to promoted growth Conditions heterogeneous in phenotypic manifestations All product candidates are investigational. Grimberg A, et al. Horm Res Paediatr. 2016;86(6):361-397. For investor communication only. Not for use in product promotion. 45 Laederich MB, et al. Curr Opin Pediatr. 2010;22(4):516-523 Not for further distribution.

Target Cells (Chondrocytes) Are in The Growth Plate Achondroplasia caused by heterozygous mutation Different conformations of the FGFR3 G380R mutated dimer Constitutive hyperactive FGFR3 signaling in the growth plate blocks growth Constitutive hyperactive FGFR3 signaling occurs in the presence and absence of ligand He et al. J Biological Chemistry, 2010 Sep 24;285(39):30103-14. He et al. (2011) J Biol All product candidates are investigational. Chem 286:13272-13281. Zhou et al. Hum Mol Genet 24:1764-1773. For investor communication only. Not for use in product promotion. 46 Figure with permission, http://cnx.org/content/col11496/1.6/ Not for further distribution.

Hyperactive FGFR3 Signaling and the Effect of CNP on Achondroplasia Are Well-Described CNP inhibits hyperactive FGFR3 signaling to counteract the block of growth plate function Copyrighted Image Wild-type ACH ACH (Normal) +CNP Adapted from Laederich MB, et al. Curr Opin Pediatr. 2010;22(4):516-523. Yasoda et All product candidates are investigational. al. (2009) Endocrinology 150:3138-3144. http://cnx.org/content/col11496/1.6/ Figures For investor communication only. Not for use in product promotion. 47 with permission Not for further distribution.

TransCon CNP Design CNP TransCon linker (active) TransCon carrier Receptor Renal clearance CNP Linker cleavage (inactive) dependent upon pH and temperature • TransCon technology is designed to provide effective shielding of CNP: – From neutral endopeptidase degradation in subcutaneous tissue and blood compartment – Minimize binding of TransCon CNP to the NPR-B and NPR-C receptors to avoid hypotension and minimize clearance • TransCon CNP is designed to provide continuous exposure of free CNP enabling exposure to the growth plate All product candidates are investigational. For investor communication only. Not for use in product promotion. 48 Breinholt VM et al. J Pharmacol Exp Ther. 2019;370(3):459-471. Not for further distribution.

Stages for TransCon CNP to Promote Growth in Achondroplasia TransCon CNP designed to promote growth in three sequential stages Copyrighted Image TransCon CNP provides Continuous free CNP Continuous CNP continuous plasma plasma exposure enables exposure in growth plate exposure of free CNP CNP exposure to the inhibits hyperactive growth plate FGFR3 signaling All product candidates are investigational. Yasoda et al. (2009) Endocrinology 150:3138-3144. For investor communication only. Not for use in product promotion. 49 http://cnx.org/content/col11496/1.6/ Figures with permission Not for further distribution.

TransCon CNP Designed to Provide Continuous Free CNP Exposure • Continuous exposure – Steady-state exposure is achieved within weeks • Dose-proportionality – Predictable continuous plasma exposure of free CNP • Low C max 1,2 – C targeted well below levels reported to induce hypotension in humans max • Once-weekly dosing All product candidates are investigational. 1. Igaki et al. (1998) Hypertension Research 21:7-13. For investor communication only. Not for use in product promotion. 50 2. Hunt et al. (1994) J Clin Endocrinol Metab 78:1428-1435. Not for further distribution.

Continuous Free CNP Plasma Exposure Enables CNP Exposure to the Growth Plate • Growth Plate Characteristics – Avascular – Hydrophilic and negatively charged matrix CNP penetration • Molecular penetration to target area to target area 1 restricted by size and charge • CNP-38 properties facilitate growth plate penetration – Small size < 4 kDa – Hydrophilic – Positively charged All product candidates are investigational. 1.Farnum et al. (2006) Anat Rec A Discov Mol Cell Evol Biol 288:91-103. For investor communication only. Not for use in product promotion. 51 http://cnx.org/content/col11496/1.6/ Figure with permission Not for further distribution.

Continuous Free CNP Exposure Inhibits Constitutive Hyperactive FGFR3 Signaling • FGFR3 hyperactive signaling in ACH is constitutive • CNP mode-of-action in ACH was revealed with sustained CNP 1-2 exposure Copyrighted Image • CNP over-expression in humans results 3-4 in increased linear growth Wild-type ACH ACH (Normal) + continuous CNP exposure 1. Yasoda et al. (2004) Nat Med 10:80-86. 2. Yasoda et al. (2009) Endocrinology All product candidates are investigational. 150:3138-3144. 3. Bocciardi et al.(2007) Hum Mutat 28:724-731. 4. Ko et al. (2015) For investor communication only. Not for use in product promotion. 52 Am J Med Genet A 167A:1033-1038. Figure used with permission Not for further distribution.

TransCon CNP Designed to Address Key Manifestations of Achondroplasia Continuous Exposure Growth Promotion Growth Plate Penetration Copyrighted Image TransCon CNP CNP properties and exposure CNP effect • Dose-Proportionality • Continuous exposure • Inhibits constitutive hyperactive FGFR3 • C targeted well below • Molecular properties facilitate max signaling levels reported to induce growth plate penetration hypotension • Promotes growth • Once-weekly dosing All product candidates are investigational. Yasoda et al. (2009) Endocrinology 150:3138-3144. For investor communication only. Not for use in product promotion. 53 http://cnx.org/content/col11496/1.6/ Figures with permission Not for further distribution.

TransCon CNP for Achondroplasia Marie-Louise C. Hartoft-Nielsen, M.D., Ph.D. Senior Medical Director, Clinical Development​

Achondroplasia – Most Frequent Skeletal Dysplasia • Achondroplasia is the most common cause of short- 1 limbed short stature • Autosomal dominant gain-of-function mutation of the 2,3,4 FGFR3 gene​ 5,6 • Estimated prevalence of ~ 4 per 100,000 births • 80% spontaneous mutations, 20% inherited ​ 1 • Approximately 250,000 people living with ACH worldwide 7 • Usually diagnosed at birth or within the first year 1. Horton WA, et al. Lancet 2007, 370(9582): 162-172, 2. Rousseau F et al. Nature 1994;371(6494):252-4 3 Shiang R et al. Cell. 1994 ;78(2):335-42, 4 Webster MK, Donoghue DJ. EMBO All product candidates are investigational. J. 1996 Feb 1;15(3):520-7 5. Coi A, AM J Med Genet Part A, 2019, 1:179: 1-8 6. Foreman PK, Am J Med For investor communication only. Not for use in product promotion. 55 Genet. 2020: 182A, 2297-2316. 7. Horton WA et al. Lancet 2007; 370: 162–72 2007 Not for further distribution.

Primary Skeletal Manifestations and Key Related Complications 1-10 Lifelong Disease Burden Manifestations Complications Interventions • Short stature • Foramen magnum • Cervicomedullary • Short limbs & rhizomelia stenosis decompression • Narrowing of foramen • Spine deformities • Grommets magnum • Spinal stenosis • Tonsillectomy/ • Midfacial hypoplasia • Sleep apnea Adenoidectomy • Frontal bossing • Recurrent otitis media • Continuous positive airway • Trident hand • Pain pressure • Obesity • Bone lengthening surgery Life expectancy impacted by risk of infant death and increased mortality in adults​ 1. Pauli, R.M. Orphanet J Rare Dis 14. 2019; 14(1):1-49 2 Langer Lo et al. Am J Roentgenol 1967 100: 12- 26, 3. Hunter AG et al. J Med Genetic. 1998; 35(9):705-12 4. Afsharpaiman S, et al., Paediatr Respir Rev. 2013;14(4):250-255. 5. Reid CS, et al. J Pediatr. 1987;110(4):522-530. 6. Schkrohowsky JG, et al. J Pediatr Orthop. 2007;27(2):119-122. 7. Saleh M et al. Orthop Clin North Am . 1991; 22:589-99 8. Hecht All product candidates are investigational. JT et al. Am J Hum Genet. 1987; 41(3): 454–464. 9. Wynn et al J, Am J Med Genet. 2007; 143A:2502-11, For investor communication only. Not for use in product promotion. 56 10. Hecht JT et al. Am J Med Genet 1988; 31:597-602 Not for further distribution.

TransCon CNP Investigational Drug Characteristics • Dose proportionality with continuous exposure over one week and low C max • Utilizes wild-type CNP peptide sequence • Designed to provide meaningful impact on clinical manifestations and burden of achondroplasia Designed to continuously inhibit hyperactive signaling of FGFR3 with low risk of cardiovascular side effects and low immunogenicity All product candidates are investigational. For investor communication only. Not for use in product promotion. 57 Data on file, Ascendis Pharma; 2019. Not for further distribution.

Non-Clinical Data Support Safety and Efficacy 2 Synchondroses of Foramen Magnum in ACH Model y367C/+ Tibial growth in young cynomolgus monkeys Fgfr3 mice 1 at 6 months (n=4/group) 7 6 Placebo 5 corrected 4 percentage change from 3 baseline 2 1 0 TransCon CNP Vehicle TransCon CNP CNP Analogue* Daily Dosing TransCon CNP 140 µg/kg/week 40 µg/kg/week 100 µg/kg/week (20 µg/kg/day) • Dose-dependent linear growth and potential to prevent premature fusion of synchondroses of foramen magnum in an ACH model • Well-tolerated in non-clinical models 1. Breinholt VM, et al. J Pharmacol Exp Ther. 2019;370(3):459-471. 2. Poster presented at ENDO 2017 All product candidates are investigational. * Refers to a synthesized molecule with a half-life of ~20 mins prepared by For investor communication only. Not for use in product promotion. 58 Ascendis Pharma Not for further distribution.

Integrated & Patient-Focused Clinical Development Program • Global natural history study in children with • Provided first achondroplasia ACHieve TransCon CNP study safety and PK in humans ACcomplisH, ACcomplisH Phase 1 China and ACcomplisH • Focus on identifying Infant • Global clinical program in relevant outcomes and children with Patient Outcomes experiences for children achondroplasia Research with achondroplasia and caregivers All product candidates are investigational. For investor communication only. Not for use in product promotion. 59 Data on File, Ascendis Pharma 2021. Not for further distribution.

Phase 1 Pharmacokinetics • Dose proportional 50 increase in Free CNP 150 µg/kg 45 exposure 75 µg/kg 40 25 µg/kg • Continuous exposure 10 µg/kg 35 and apparent T of 1/2 30 ~ 120 hours in adults * Free CNP (pM) 25 (Mean ±SEM) 20 15 10 5 0 0 24 48 72 96 120 144 168 Hours Continuous and dose-dependent exposure, T supports weekly dosing ½ All product candidates are investigational. *CNP measured as CNP 38 For investor communication only. Not for use in product promotion. 60 Ota et al. Oral presentation at ISDS 2019. Not for further distribution.

TransCon CNP Was Well-Tolerated Up to 150 µg/kg in Phase 1 • Mean resting blood pressure 40 60 and heart rate were unchanged from pre-dose 40 30 • Mean orthostatic changes in 20 Mean plasma Mean orthostatic vital signs appear unrelated to concentration change in BP 20 0 (mmHg) of free CNP-38 CNP exposure; consistent with (pM) placebo -20 10 • No serious AEs were reported -40 • Injections were well tolerated 0 -60 0 8 16 24 32 40 48 56 64 72 • No anti-CNP antibodies Time since dosing (hours) detected 150 µg/kg SBP DBP Well-tolerated with mean orthostatic vital signs unchanged All product candidates are investigational. For investor communication only. Not for use in product promotion. 61 Data on file. Not for further distribution.

Clinical Development Program ONGOING • Natural history study • Age 0-8 years • N=234 • 14 countries IND or equivalent submission ONGOING ONGOING planned for Q2 2022 • China, multiple dose • Global, multiple dose, • Global, multiple dose study early intervention study study • Age 2-10 years • Age 2-10 years • Age 0-2 years • N=57 • N~60 • N~30 All product candidates are investigational. For investor communication only. Not for use in product promotion. 62 Not for further distribution.

TransCon CNP: Phase 2 Trial Design Up to 60 children (ages 2–10 years) with achondroplasia Open Label 12 subjects randomized in each dose cohort in a blinded manner TransCon CNP Extension vs. placebo (3:1 Period to 6 µg/kg 20 µg/kg 50 µg/kg 100 µg/kg >100 µg/kg randomization) evaluate long-term Data Monitoring Committee reviews blinded data after each dose cohort safety and efficacy Key Secondary/Additional Endpoints Primary Endpoint • Change in body proportionality • Annualized height velocity • Patient reported outcome (PRO) measures • Exploratory biomarkers evaluated ClinicalTrials.gov. All product candidates are investigational. https://clinicaltrials.gov/ct2/show/NCT04085523?term=ACcomplisH&draw=2&rank=5. For investor communication only. Not for use in product promotion. 63 Accessed 05/23/2021. Not for further distribution.

Baseline Characterics ACcomplisH - Enrollment Complete Demographics Cohort 1 (N = 13) Cohort 2 (N = 15) Cohort 3 (N = 14) Cohort 4 (N = 15) Age (years) Mean (SD) 6.4 (2.82) 6.2 (3.13) 5.6 (2.91) 5.5 (2.51) Age Group (years), n (%) 2–5 years 5 (38.5) 7 (46.7) 6 (42.9) 6 (40.0) 5–8 years 4 (30.8) 5 (33.3) 4 (28.6) 6 (40.0) > 8 years 4 (30.8) 3 (20.0) 4 (28.6) 3 (20.0) Sex, n (%) 7 (53.8) 5 (33.3) 5 (35.7) 7 (46.7) Female 6 (46.2) 10 (66.7) 9 (64.3) 8 (53.3) Male Age at ACH Diagnosis, n (%) 0 1 (6.7) 4 (28.6) 0 Pre-Birth 4 (30.8) 3 (20.0) 2 (14.3) 2 (13.3) At Birth 9 (69.2) 9 (60.0) 7 (50.0) 8 (53.3) 0–6 months 0 2 (13.3) 1 (7.1) 1 (6.7) 6–12 months 0 0 0 1 (6.7) > 12 months Height SDS –5.4 (1.10) –5.0 (0.66) –4.7 (0.82) –4.8 (0.79) Mean (SD) All product candidates are investigational. For investor communication only. Not for use in product promotion. 64 Data on file, Ascendis Pharma; Q4 2021 Not for further distribution.

Baseline Characterics ACcomplisH - Enrollment Complete Demographics Cohort 1 (N = 13) Cohort 2 (N = 15) Cohort 3 (N = 14) Cohort 4 (N = 15) Age (years) Mean (SD) 6.4 (2.82) 6.2 (3.13) 5.6 (2.91) 5.5 (2.51) Age Group (years), n (%) 2–5 years 5 (38.5) 7 (46.7) 6 (42.9) 6 (40.0) 5–8 years 4 (30.8) 5 (33.3) 4 (28.6) 6 (40.0) > 8 years 4 (30.8) 3 (20.0) 4 (28.6) 3 (20.0) Sex, n (%) Female 7 (53.8) 5 (33.3) 5 (35.7) 7 (46.7) Male 6 (46.2) 10 (66.7) 9 (64.3) 8 (53.3) Age at ACH Diagnosis, n (%) Pre-Birth 0 1 (6.7) 4 (28.6) 0 At Birth 4 (30.8) 3 (20.0) 2 (14.3) 2 (13.3) 0–6 months 9 (69.2) 9 (60.0) 7 (50.0) 8 (53.3) 6–12 months 0 2 (13.3) 1 (7.1) 1 (6.7) > 12 months 0 0 0 1 (6.7) Height SDS –5.4 (1.10) –5.0 (0.66) –4.7 (0.82) –4.8 (0.79) Mean (SD) All product candidates are investigational. For investor communication only. Not for use in product promotion. 65 Data on file, Ascendis Pharma; Q4 2021 Not for further distribution.

Baseline Characterics ACcomplisH - Enrollment Complete Demographics Cohort 1 (N = 13) Cohort 2 (N = 15) Cohort 3 (N = 14) Cohort 4 (N = 15) Age (years) Mean (SD) 6.4 (2.82) 6.2 (3.13) 5.6 (2.91) 5.5 (2.51) Age Group (years), n (%) 2–5 years 5 (38.5) 7 (46.7) 6 (42.9) 6 (40.0) 5–8 years 4 (30.8) 5 (33.3) 4 (28.6) 6 (40.0) > 8 years 4 (30.8) 3 (20.0) 4 (28.6) 3 (20.0) Sex, n (%) 7 (53.8) 5 (33.3) 5 (35.7) 7 (46.7) Female 6 (46.2) 10 (66.7) 9 (64.3) 8 (53.3) Male Age at ACH Diagnosis, n (%) 0 1 (6.7) 4 (28.6) 0 Pre-Birth 4 (30.8) 3 (20.0) 2 (14.3) 2 (13.3) At Birth 9 (69.2) 9 (60.0) 7 (50.0) 8 (53.3) 0–6 months 0 2 (13.3) 1 (7.1) 1 (6.7) 6–12 months 0 0 0 1 (6.7) > 12 months Height SDS –5.4 (1.10) –5.0 (0.66) –4.7 (0.82) –4.8 (0.79) Mean (SD) All product candidates are investigational. For investor communication only. Not for use in product promotion. 66 Data on file, Ascendis Pharma; Q4 2021 Not for further distribution.

ACcomplisH – Continuous Exposure with Low C max Pharmacokinetics • Continuous exposure over the weekly dosing interval (Free CNP T ~ 110 hours) ½ • Dose proportionality • Steady-state plasma concentration of free CNP reached after four doses Free CNP (pM) • C well below levels reported to induce max 1,2 hypotension in humans Time (Weeks) Red represents modeling data built on Phase 1 PK Black represents actual data from ACcomplisH Trial All product candidates are investigational. 1. Igaki et al. (1998) Hypertension Research 21:7-13. For investor communication only. Not for use in product promotion. 67 2. Hunt et al. (1994) J Clin Endocrinol Metab 78:1428-1435. Not for further distribution.

ACcomplisH - Preliminary Safety Profile (N=57)* • No withdrawals or discontinuations for any reason • No serious adverse events related to trial drug • 13 AEs related to trial drug or procedures – Of these, eight mild and transient injection site reactions (in over 1900 injections) • Injections generally well tolerated in all dose cohorts • No AEs related to orthostatic blood pressure changes • No treatment-emergent anti-CNP antibodies detected Well-tolerated in children with achondroplasia up to 65 weeks follow-up All product candidates are investigational. For investor communication only. Not for use in product promotion. 68 *As per December 8 2021 Not for further distribution.

Upcoming Trials * • Objectives: Efficacy (AHV at week 52), • Objective: Early intervention to prevent growth safety, PK disorder progression; safety, PK • Design: Randomized, double-blind, • Design: Pending interactions with regulatory placebo-controlled trial agencies • Age: 2-10 years • Age: 0-2 years • Doses: 50 and 100 µg/kg/week selected • Doses: TBD from blinded data from ACcomplisH Trial • Region: Global (US, Europe and Oceania) • Region: Greater China • Number of subjects: 30 (planned) • Number of subjects: 60 • Status: IND or equivalent planned for Q2 2022 • Status: Enrolling All product candidates are investigational. For investor communication only. Not for use in product promotion. 69 *In collaboration with VISEN Pharmaceuticals Not for further distribution.

1-6 The Patient & Caregiver Experience of Achondroplasia • Physical signs and symptoms • Functioning and daily life • School participation • Emotional well-being • Social well-being We are committed to understanding achondroplasia beyond growth 1. Bloemeke, J, et al. Qual Life Res 28, 2553–2563 (2019). 2. Bloemeke J,. et al. Disabil Rehabil. 2019 Jul;41(15):1815-1825. ​3. Dogba MJ, et al. Health Qual Life Outcomes. 2014 Oct 25;12:151. 4. Gollust SE, et al. Am J Med Genet A. 2003 Aug 1;120A(4):447-58. 5. All product candidates are investigational. Sommer R, et al. J. Disabil Rehabil. 2017 Dec;39(24):2499-2503. 6. Pfeiffer KM, et al. Am J For investor communication only. Not for use in product promotion. 70 Med Genet. 2020;185(1):33-45.​ Not for further distribution.

TransCon CNP Clinical Program Is Progressing • ACcomplisH enrollment complete (N=57) • Interim blinded data informed dose selection of 50 and 100 mg/kg/week for ACcomplisH China • Preliminary PK and safety data on TransCon CNP suggest continuous CNP is well- tolerated across all doses administered • ACcomplisH Infant in children 0–2 years of age; evaluate early intervention in ACH to prevent growth disorder progression; safety, PK • Upcoming milestones: – ACcomplisH Infants Trial IND equivalent submission planned for Q2 2022 – ACcomplisH Trial top-line data anticipated in Q4 2022 All product candidates are investigational. For investor communication only. Not for use in product promotion. 71 Not for further distribution.

™ TransCon Technology for Intratumoral Administration Kennett Sprogøe, Ph.D. SVP, Head of Innovation and Research

TransCon Positioned to Potentially 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 No Tumor Cold Tumor Hot Tumor Tumor cells X Immune-suppressing cells Cytotoxic T cells and other cancer fighters Applicable to diverse drug classes and mechanisms of action; opportunity for combination approaches All product candidates are investigational. For investor communication only. Not for use in product promotion. 73 Not for further distribution.

Two Clinical Candidates – Potential to Address Multiple Steps of the Immunity Cycle TransCon IL-2 b/g TransCon TLR7/8 Agonist for IT delivery and enhanced tumor-antigen presentation Designed to enhance antigen presentation and, thereby, promote activation of cytotoxic immune TransCon cells and drive systemic immune activation TLR7/8 Agonist TransCon IL-2 b/g for systemic activation of TransCon IL-2 b/g tumor-antigen specific cytotoxic cells Designed to aid T cell and NK cell expansion and infiltration of immune cells into tumors Additional TransCon Candidates TransCon TLR7/8 Agonist New TransCon candidates with the potential to affect all steps in the immunity cycle Combination approaches to enable impact on all critical steps of anti-tumor response All product candidates are investigational. For investor communication only. Not for use in product promotion. 74 Not for further distribution.

TransCon IL-2 b/g: Soluble Carrier, as in Endocrine Pipeline TransCon carrier TransCon linker IL-2 b/g (active) Receptor TransCon IL-2 β/γ (Prodrug) Renal clearance IL-2 b/g Linker cleavage (inactive) dependent upon pH and temperature TransCon IL-2 b/g is designed to provide sustained, long-lasting exposure of a highly-potent, proprietary IL-2 variant using the linker and carrier from TransCon hGH All product candidates are investigational. For investor communication only. Not for use in product promotion. 75 Not for further distribution.

TransCon TLR7/8 Agonist: Sustained Intratumoral (IT) Release of Resiquimod Local depot of drug loaded Linker cleavage under TransCon hydrogel carrier physiological conditions Parent drug is transiently Following injection, the Designed to provide sustained bound to TransCon linker- linker is designed to high local drug levels with low hydrogel carrier, which autocleave at a specific systemic exposure; hydrogel inactivates, shields parent rate to predictably release degrades into small polymers that are renally cleared drug and prevents clearance unmodified parent drug All product candidates are investigational. For investor communication only. Not for use in product promotion. 76 Not for further distribution.

TransCon IT Represents a Potential Paradigm Shift in Cancer Therapy Short tumor exposure Systemic Parent • Transient effect in tumor exposure drug IT • Significant systemic toxicity Days/Weeks Long tumor exposure TransCon IT • Sustained activity in the tumor Low systemic • Minimized systemic toxicity exposure Days/Weeks TransCon technology provides potential for sustained modulation of tumor microenvironments with infrequent dosing and minimized systemic toxicity All product candidates are investigational. For investor communication only. Not for use in product promotion. 77 Not for further distribution. Concentration Concentration

TransCon IT Designed for Local and Abscopal Anti-Tumor Effects Designed to Enable Immune Activation in the Draining Lymph Nodes Cytotoxic T effector Cells Primed in Lymph Nodes Capable of Targeting Abscopal Tumors All product candidates are investigational. For investor communication only. Not for use in product promotion. 78 Adapted from Yeo et al, Front. Immunol., 2017; and Marabelle et al., Ann Onc, 2017 Not for further distribution.

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 10000.0 Single TransCon IT Dose in Mice 1000.0 Concentration Tumor concentration of released drug 100.0 (ng/mL±SD) Systemic concentration of released drug 10.0 1.0 0.1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Time (days) TransCon IT is designed to stay in the tumor and slowly release the drug, ensuring high tumor drug concentration and low systemic exposure All product candidates are investigational. For investor communication only. Not for use in product promotion. 79 Data on file. Not for further distribution.

Modeled Volume of Hydrogel in Injected Tumor Model of Intratumoral Hydrogel M o d e l o f I n t r a t u m o r a l H y d r o g e l Accumulation and Degradation A c c u m u l a t i o n a n d D e g r a d a t i o n 5 Q3W dosing leads to 500 accumulation of 4-5 depots 4 400 within the tumor at steady state Volume increase 3 300 [%] 2 200 Upon cessation of dosing, the hydrogel degrades and is 1 100 Arrow Denotes cleared from the tumor site IT Injection 0 0 9 0 1 8 0 2 7 0 t i m e [ d ] * In vitro data; Data on file Following injection, the hydrogel carrier disintegrates into small polymer fragments after approximately 3 months* All product candidates are investigational. For investor communication only. Not for use in product promotion. 80 Not for further distribution.

Algorithm for Product Innovation: Building an Oncology Pipeline Clinically Established Higher Value, Unmet TransCon Clearly Large Validated Clinical & Medical Technology Differentiated Addressable Lower Risk Parent Regulatory Need Suitability Product Market Drug Pathway Pipeline We are continuing to apply our successful algorithm applied in endocrinology to build a rd pipeline in oncology and we are committed to entering a 3 therapeutic area All product candidates are investigational. For investor communication only. Not for use in product promotion. 81 Not for further distribution.

Opportunity for TransCon TLR7/8 Agonist in Solid Tumors Efficacy • Each injection designed to provide sustained exposure in the tumor to enhance immune activation TransCon TLR7/8 Agonist • Systemic immune activation may lead to abscopal tumor effects Safety • Low systemic toxicity expected to reduce dose-limiting adverse events • Infrequent dosing designed to improve practicality and reduce injection-related complications Designed for superior Broad application efficacy with minimal • Essentially all solid tumor lesions that can be biopsied systemic toxicity may be considered for injection All product candidates are investigational. For investor communication only. Not for use in product promotion. 82 Not for further distribution.

Potential Paradigm Shift in How Cancer Is Treated • Oncology pipeline using TransCon technologies that may enable a new treatment paradigm, based on well-known biology • Two clinical-stage product candidates with potentially best-in-class properties using systemic and localized TransCon technology – TransCon TLR7/8 Agonist designed for IT, long-term sustained release for superior efficacy with minimal systemic adverse events – TransCon IL-2 b/g designed for optimized IL-2Rb/g bias and potency, combined with low C and long exposure max • TransCon technology offers a new treatment paradigm for oncology, providing both systemic and IT sustained delivery options with potential for superior efficacy and safety All product candidates are investigational. For investor communication only. Not for use in product promotion. 83 Not for further distribution.

TransCon TLR7/8 Agonist TransCon TLR7/8 Clinical Update Agonist Stina Singel, M.D., Ph.D. Head of Clinical Development, Oncology

Unmet Medical Need Remains High Despite Advancements • Immunotherapy has given hope for dramatic improvement in cancer treatment… • But most cancer patients today are not benefiting from immunotherapy • U.S. cancer patients eligible for checkpoint inhibitors (CPI) increased from 1.5% in 2011 to 43.6% in 2018 Unmet need • Percentage of patients estimated to respond to CPI was 0.1% in 2011 and increased to 12.5% in 2018 Immunotherapy has “raised the tail” for multiple tumor types Time* More effective therapies are urgently needed All product candidates are investigational. * Graph is illustrative and does not represent specific observed data. For investor communication only. Not for use in product promotion. 85 Haslam A and Prasad V. JAMA Netw Open. 2019;2(5):e192535. Not for further distribution. Overall Survival Metastatic Cancer

Toll-Like Receptors (TLRs): Well-Validated Targets for Activation of 1 Innate and Adaptive Immunity • Activate innate immunity in particular antigen presenting cells (APCs) • Prime and expand cytolytic and helper T cells • Inhibit suppressive mechanisms limiting anti-tumor responses • Resiquimod has been clinically evaluated 2,3 as a potent TLR7/8 Agonist TLRs activate several key pathways critical in host defense against tumors 1. Bourquin C, et al. Pharmacol Res, 2020; 154:104192 All product candidates are investigational. 2. Vasilakos J and Tomai M. Exp Rev Vaccines, 2013; 12:809-819. For investor communication only. Not for use in product promotion. 86 3. Rook A, et al. Blood. 2015;126(25):2765. Not for further distribution.

Limitations of TLR Agonists in Clinical Setting 1 • Systemic administration leads to high toxicity such as cytokine release syndrome • Previous IT approaches cannot deliver prolonged exposure of active drug levels needed for anti-tumor activity – Consistent with short exposure, pharmacodynamic effects of previous IT TLR agonists in the 2,3 tumor have only been reported at ~24 hours post dose Sustained IT exposure of resiquimod is likely needed for therapeutic benefit while minimizing systemic toxicity All product candidates are investigational. 1 2 Pockros et al. 2007 J of Hepatology 47: 174-182; Babiker et al. ESMO 2020, abs 1031P; For investor communication only. Not for use in product promotion. 3 87 Diab et al. SITC 2020, abs 368 Not for further distribution.

Clinical Development Strategy in Oncology to Take Advantage of the Clinically Validated TransCon Platform BUILD ESTABLISH EXPAND safety and tolerability proof-of-concept to other indications profile while identifying efficacy in indications based on appropriate dose of high unmet medical • Unmet need need • Across various • Emerging data and indications • Indications with changing treatment strong scientific • As monotherapy and landscape rationale in combination with standard of care • Available benchmark data • In combination with internal pipeline All product candidates are investigational. For investor communication only. Not for use in product promotion. 88 Not for further distribution.

Status Update on transcendIT-101: TransCon TLR7/8 Agonist First-in-Human Trial Dose Escalation (“3+3” Design) Dose Expansion Part 1: Part 2: Part 3: Monotherapy Combination with pembro Combination with pembro HNSCC at RP2D Any solid tumor, Indications with known or any line potential pembro activity Part 3: Combination with pembro Objectives: Other HPV-associated • Safety and tolerability; define MTD and RP2D Tumors at RP2D • Pharmacokinetics/pharmacodynamics (PK/PD) • Preliminary anti-tumor efficacy (ORR, duration of and time to response) All product candidates are investigational. Abbreviations: recommended phase 2 dose (RP2D), maximum tolerated dose For investor communication only. Not for use in product promotion. 89 (MTD), overall response rate using RECIST 1.1 (ORR) Not for further distribution.

Initial Indications of HPV-associated Cancers Selected Based on Strong Scientific Rationale 1 TLRs and HPV-associated cancers Dose Expansion Other indications will Combination with CPI be added based on HPV-associated tumors: • Unmet need • HNSCC • Emerging data and • Others (anal, cervical, changing treatment vulvar, penile, vaginal) landscape HNSCC: HPV+ prevalence rising -- for every 2 new cases of HPV- 2 oropharyngeal carcinoma diagnosed, 5 new cases HPV+ Anal, cervical, vulvar, penile, vaginal: vast majority (>70-90%) are HPV+ HNSCC: head and neck squamous cell carcinoma; HPV: human papillomavirus All product candidates are investigational. 1 Barros M, et al. J Immunology Res. 2018; 2912671:1-17. For investor communication only. Not for use in product promotion. 2 90 Mahal B, et al. Cancer Epidemiol Biomarkers Prev. 2019; 10:1660-1667. Not for further distribution.

Interim Status Update on transcendIT-101: TransCon TLR7/8 Agonist First-in-Human Trial Dose Escalation (“3+3” Design) Dose Expansion Part 1: Part 2: Part 3: Monotherapy Combination with pembro Combination with pembro HNSCC at RP2D Any solid tumor, Indications with known or any line potential pembro activity Part 3: Combination with pembro Dose level 1: n=3 Dose level 1: n=3 Other HPV-Associated Status 1 efficacy evaluable* 2 efficacy evaluable* Tumors at RP2D Update Dose level 2: Enrolling Dose level 2: Enrolling Dose escalation ongoing with dose expansion expected to start enrollment in Q2 2022 All product candidates are investigational. For investor communication only. Not for use in product promotion. 91 * Efficacy evaluable: at least 1 post-baseline tumor assessment Not for further distribution.

transcendIT-101: Low Systemic Exposure with Half-life of ~7 Days Resiquimod mean (+SD) plasma concentrations following one intratumoral injection Plasma concentration where cytokine release syndrome has been observed* • Plasma concentrations 15-fold below levels where cytokine release syndrome has been observed (~4000 pg/mL*) Mean plasma conc. (pg/mL) • Mean systemic half-life of resiquimod is ~7 days Time (day) Peripheral PK indicates sustained release of resiquimod with a half-life of ~7 days and systemic exposure with wide safety margin All product candidates are investigational. Mean of n=7 (6 at dose level 1 and 1 at dose level 2) For investor communication only. Not for use in product promotion. 92 * Pockros PJ et al. J Hepatol. 2007;47(2):174-182. Not for further distribution.

Demographic and Safety Data* Select Demographics Monotherapy (n=5) Combination (n=3) Tumor types Melanoma (n=3) Melanoma (n=1) TNBC (n=1) Basal Cell Carcinoma (n=1) Pancreatic (n=1) Pancreatic (n=1) Median prior anti-cancer treatment regimens 3 2 Prior anti-PD(L)1 4 (80%) 2 (67%) Overview of Safety Subjects with at least 1 AE 4 (80%) 2 (67%) Subjects with at least one SAE 3 (60%) Related: 0 1 (33%) Related: 0 Subjects with at least one ≥3 AE 3 (60%) Related: 0 1 (33%) Related: 0 Subjects with an AE leading to study drug 0 0 withdrawn or study discontinuation Subjects with Death related to AE 0 0 TransCon TLR7/8 Agonist is well-tolerated as monotherapy or in combination with pembrolizumab, consistent with low systemic exposure All product candidates are investigational. For investor communication only. Not for use in product promotion. 93 *Datacut date: 16 Nov 2021 Not for further distribution.

Initial Interim Data Indicate TransCon TLR7/8 Agonist Is Well-Tolerated as Monotherapy or in Combination with Pembrolizumab • No dose-limiting toxicities observed • Limited safety-evaluable population (n=8) so far indicates no systemic side effects related to TransCon TLR7/8 Agonist ‒ Consistent with low systemic exposure of resiquimod • Transient, mild injection site-related reactions (Grade 1/2) are the only related AEs ‒ 2 out of 5 patients treated with monotherapy ‒ No injection site reactions have been reported so far for 3 patients treated with combination treatment All product candidates are investigational. For investor communication only. Not for use in product promotion. 94 Datacut date: 16 Nov 2021 Not for further distribution.

transcendIT-101: Study Status N=8 treated with study treatment as of 16 Nov 2021* – 3 efficacy evaluable patients with at least 1 post-baseline tumor assessment – 2 discontinued due to progressive disease (before first tumor assessment at week 9) – 1 discontinued due to physician decision (patient left study for hospice care before week 9) – 2 patients ongoing but have not yet reached first efficacy assessment at week 9 TransCon TLR7/8 Agonist Tumor type (# prior anti-cancer Prior PD(L)1 Dose Level 1 treatment regimens) Monotherapy Melanoma (2) yes Combination with pembro Pancreatic Cancer (2) no Combination with pembro Basal Cell Carcinoma (2) yes Datacut date:16 Nov 2021 with tumor response data only updated on 3 Dec 2021 due to new pathology data; All product candidates are investigational. * Median follow up (time from study treatment start to the date of death or the date patient is last For investor communication only. Not for use in product promotion. 95 known to be alive): 59 d (range 15-190) Not for further distribution.

Early Signs of Clinical Activity from Efficacy-Evaluable Patients (#1) Best Overall Response per RECIST v1.1 Available On-Treatment Pathology Patient Profile #1 (latest investigator assessment) Tumor Type: Melanoma uPR (week 27) Injected lesion: 3 core biopsies at week 27 after 9 doses showed Prior Treatment Regimens: 2 Target lesions Baseline wk9 wk18 wk27 tumor cells found in up to 50% of total tissue; Prior PD(L)1: yes—pembro Injected (mm) 25 24 24 30 focal foreign material (hydrogel carrier) surrounded Non-injected (mm) 11 10 9 0 by granulomatous inflammation Treated with: TransCon TLR7/8 Monotherapy Dose Non-injected lesion: Level 1 Punch biopsy at week 27 (lesion site previously marked) showed mild chronic inflammation, reactive changes, no evidence of malignancy Pathological confirmation of complete response in non-injected lesion indicates abscopal effect of monotherapy TransCon TLR7/8 Agonist in a patient previously treated with pembro All product candidates are investigational. For investor communication only. Not for use in product promotion. 96 uPR = unconfirmed partial response; Datacut date: 3 Dec 2021 Not for further distribution.

Early Signs of Clinical Activity from Efficacy-Evaluable Patients (#2) Best Overall Response per RECIST v1.1 Patient Profile #2 Available On-Treatment Pathology (latest investigator assessment) Tumor Type: Pancreatic Cancer SD (week 9) Injected lesion: 3 core biopsies at week 7 after 1 dose Prior Treatment Regimens: 2 Target lesions Baseline wk9 showed no tumor present; minimal Prior PD(L)1: no Injected once in Cycle 1 (mm) 22 30 lymphohistiocytic reaction Non-injected (mm) 90 Treated with: TransCon TLR7/8 Injected since Cycle 2 (mm) 90 Dose Level 1 Combination with Pembro Pathological evaluation after a single dose suggests early and potentially deep response in injected tumor All product candidates are investigational. For investor communication only. Not for use in product promotion. 97 SD = stable disease; Datacut date: 3 Dec 2021 Not for further distribution.

Early Signs of Clinical Activity from Efficacy-Evaluable Patients (#3) Best Overall Response per RECIST v1.1 Patient Profile #3 Available On-Treatment Pathology (latest investigator assessment) Tumor Type: Basal Cell SD (week 9) Injected lesion: Carcinoma Punch biopsy at week 9 after 3 doses Target lesions Baseline wk9 showed atypical basaloid proliferation at base Prior Treatment Regimens: 2 Injected (mm) 42 47.5 of biopsy. Prior PD(L)1: yes—cemiplimab Non-injected (mm) 17 18.4 No evidence of malignancy. progression immediately prior to enrollment Treated with: TransCon TLR7/8 Dose Level 1 Combination with Pembro Pathological evaluation at time of first tumor assessment suggests early and potentially deep response in injected tumor in a patient who progressed on anti-PD1 All product candidates are investigational. For investor communication only. Not for use in product promotion. 98 SD = stable disease; Datacut date: 3 Dec 2021 Not for further distribution.

Target Activation of Key Immunological Pathways Maintained Through at Least 7 Days Post-Dose in Injected and Non-Injected Lesions Gene Expression at 7 Days After 1 Dose of TransCon TLR7/8 Agonist • Target engagement of TLR7/8 Agonist ‒ Consistent increase of IRF-7 • Innate immune activation IFN-related ‒ Strong increase in CXCL10 expression genes • Interferon (IFN) pathway activation ‒ Consistent increase of STAT1 expression • Data consistent across different tumor types ‒ Melanoma, Basal Cell Carcinoma, Pancreatic Cancer • Similar effects observed in non-injected lesions Consistent and robust immune activation in tumor tissue is observed for at least 7 days post dose * Pathology data available Log2 fold changes ** Dose Level 2 (all others at Dose Level 1); each column represents 1 patient All product candidates are investigational. For investor communication only. Not for use in product promotion. 99 Not for further distribution.

Sustained Upregulation of IFN-Related Genes in Tumor Tissue with Repeat Dosing IRF7 STAT1 CXCL10 Injected Lesions Non-injected Lesions * Pembro is administered on C1D8 after biopsy and on C2D1 ** Dose Level 2 (all others at Dose Level 1) • Downstream of TLR7 and TLR8 • Central signaling molecule in the • Induced by IFN-γ IFN-I pathway • Upregulation indicates target • Upregulation indicates • Upregulation indicates IFN engagement of the innate engagement of TLR7/8 agonist pathway activation immune system Sustained immune activation of key immunologic pathways is maintained with repeat dosing All product candidates are investigational. For investor communication only. Not for use in product promotion. 100 Not for further distribution.

TransCon Represents a Potential Paradigm Shift in Cancer Treatment • Early data from ongoing TransCon TLR7/8 Agonist first-in-human trial (transcendIT-101) indicated: – Early signs of activity in three out of three evaluable patients including those previously treated with checkpoint inhibitors – Monotherapy activity – Consistent and robust target engagement – Well-tolerated safety profile – Expected low systemic exposure based on early PK data • TransCon TLR7/8 Agonist has the potential for: – Sustained immune activation – Systemic anti-tumor response with infrequent dosing • Create a pipeline using TransCon technologies that may enable a new treatment paradigm building upon well-known biology – TransCon IL-2b/g first-in-human trial (IL beliege; NCT05081609) is now open for enrollment All product candidates are investigational. For investor communication only. Not for use in product promotion. 101 Not for further distribution.

Q&A Session Email questions to: IR@ascendispharma.com