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ASCENDIS PHARMA A/S Virtual R&D Program Update

Key Takeaway: 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,

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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 Sprog e, 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 M ller 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 Sprog e, 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
Opening Comments Jan M ller Mikkelsen President & Chief
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
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 g/day Screening Titration of TransCon PTH and conventional therapy with the TransCon PTH 18 g/day
4 weeks goal to maintain normocalcemia TransCon PTH 21 g/day TransCon PTH 6-60 g/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 g/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
Last updated: Dec 14, 2021