Full Press Release Details
Ascendis Pharma A/S 39th Annual
J.P. Morgan Healthcare Conference January 11, 2021 All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation. Exhibit 99.1
Cautionary Note On Forward-Looking
Statements This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, such as statements regarding our future results of operations and financial position,
including our business strategy, prospective products, availability of funding, clinical trial results, product approvals and regulatory pathways, collaborations, licensing or other arrangements, the scope, progress, results and costs of developing
our product candidates or any other future product candidates, the potential market size and size of the potential patient populations for our product candidates, timing and likelihood of success, plans and objectives of management for future
operations, the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates, future results of current and anticipated products, and the future operations of VISEN Pharmaceuticals are
forward-looking statements. These forward-looking statements are based on our current expectations and beliefs, as well as assumptions concerning future events. These statements involve known and unknown risks, uncertainties and other factors that
could cause our actual results to differ materially from the results discussed in the forward-looking statements. These risks, uncertainties and other factors are more fully described in our reports filed with or submitted to the Securities and
Exchange Commission, including, without limitation, our most recent Annual Report on Form 20-F filed with the SEC on April 3, 2020 particularly in the sections titled "Risk Factors" and "Management's Discussion and Analysis
of Financial Condition and Results of Operations". In light of the significant uncertainties in our forward-looking statements, you should not place undue reliance on these statements or regard these statements as a representation or warranty
by us or any other person that we will achieve our objectives and plans in any specified timeframe, or at all. Any forward-looking statement made by us in this presentation speaks only as of the date of this presentation and represents our estimates
and assumptions only as of the date of this presentation. Except as required by law, we assume no obligation to update these statements publicly, whether as a result of new information, future events, changed circumstances or otherwise after the
date of this presentation. This presentation concerns product candidates that are or have been under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration, European Medicines Agency or
other foreign regulatory authorities. These product candidates are currently limited by U.S. Federal law to investigational use, and no representations are made as to their safety or effectiveness for the purposes for which they are being
investigated. Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo and TransCon are trademarks owned by the Ascendis Pharma Group. January 2021 Ascendis Pharma A/S.
Company Overview Create best-in-class
products addressing unmet medical needs by applying TransCon technologies to parent drugs with clinical proof-of-concept or clinically validated pathways Endocrinology rare disease TransCon hGH: Pediatric growth hormone deficiency (GHD): BLA
and MAA submitted, phase 3 trials in China1 ongoing and Japan initiated Adult GHD: Global phase 3 foresiGHt Trial ongoing TransCon PTH: Adult hypoparathyroidism (HP) phase 3 PaTHway Trial in North America and Europe ongoing TransCon CNP:
Achondroplasia phase 2 trials: ACcomplisH Trial ongoing and ACcomplisH China Trial1 initiated Oncology TransCon TLR7/8 Agonist: IND filed TransCon IL-2 b/g: IND filing or similar expected in Q3 2021 As of September 30, 2020, cash, cash equivalents
and marketable securities of 957.5 million 1 Conducted by VISEN Pharmaceuticals. BLA = Biologics License Application. MAA = Marketing Authorisation Application.
Vision 3x3: Building a Leading
BioPharma Company Our Goal is to Achieve Sustainable Growth through Multiple Approaches Obtain regulatory approval for three independent Endocrinology Rare Disease products TransCon hGH for pediatric growth hormone deficiency TransCon PTH for adult
hypoparathyroidism TransCon CNP for achondroplasia Grow Endocrinology Rare Disease pipeline through Global clinical reach Pursuing 9 total indications, label optimization, and life cycle management New endocrinology products Establish global
commercial presence for our Endocrinology Rare Disease area Build integrated commercial organization in North America and select European countries Establish global commercial presence through partners with local expertise and infrastructure Advance
a high value oncology pipeline with one IND or similar filing each year Create a third independent therapeutic area with a diversified pipeline
Diverse Pipeline of Independent Product
Candidates 1Excludes rights granted to VISEN Pharmaceuticals in Greater China. 2In phase 3 development for pediatric growth hormone deficiency in Greater China through strategic investment in VISEN Pharmaceuticals. 3US PDUFA June 25,
Endocrinology Rare Disease All product
candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.
TransCon hGH: Once-Weekly Replacement
Therapy All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.
Growth Hormone Supports Overall
Endocrine Health 1de Boer, H. et al. J. Clin. Endocrinol. Metab. 1997; 82(7): 2032-2036. 2Rutherford, O. M. et al. Clin. Endocrinol 1991; 34(6): 469-475. 3Colle, M., J. Auzerie. Horm. Res. 1993; 39(5-6): 192-196. 4Johannsson, G., et al. J. Clin.
Endocrinol. Metab. 1999; 84(12): 4516-4524. 5Stabler, B. et al. Horm. Res. 1996; 45(1-2) 30-33 6Leonga, G., Johannsson, G. Horm. Res. 2003; 60(suppl1): 78-85 7Colao, A. et al. J. Clin. Endocrinol. Metab. 2002; 87(8): 3650-3655. 8Bex, M., Bouillon,
R. Horm. Res. 2003; 60(suppl3): 80-86. Fractures8 Ultimate Height Achievement1 Cardiovascular Disease6,7 Mental Health5 Body Composition2,3,4 Daily hGH addresses all the symptoms of the disease; long-acting growth hormone products must retain the
properties of hGH to adequately address the totality of the disease
Pediatric GHD Patients Continue
Approaching Normal Height Children initially treated with TransCon hGH maintained an advantage in height SDS improvement Height SDS Change from Baseline (LS Mean + SE) TransCon hGH Genotropin Genotropin switch to TransCon hGH heiGHt Trial subjects
rolled over into enliGHten Trial (long-term extension) *Denotes treatment difference resulted in a nominal P value < 0.05. Maniatis A et al. Oral presentation at ENDO 2020 and Data on file.
Key Learnings from TransCon hGH
Pediatric Clinical Trials TransCon hGH demonstrated a safety profile comparable to that of a daily hGH1 TransCon hGH demonstrated superior AHV2 compared to a daily hGH with a PK profile2 of released hGH that may lead to more efficient
utilization by target tissues Data suggest hGH released from TransCon hGH maintains the same mode of action as daily hGH and preserves the biological balance between hGH and IGF-1 effects1,2,3,4 TransCon hGH and a daily hGH demonstrated
similar relationship between change in height SDS and change in average IGF-1 SDS3,4,5 TransCon hGH showed predictable linear IGF-1 response to dose titrations5 TransCon hGH demonstrated consistent safety and efficacy profile following switch from
daily hGH in both fliGHt and enliGHten trials1 1Maniatis A et al. Oral presentation at ENDO 2020. 2Thornton P, et al. Oral presentation at ENDO 2019. 3Chatelain P, et.al. J Clin Endocrinol Metab 2017, 102(5): 1673 - 1682. 4Vlachopapadopoulou
et al. Oral presentation at ESPE 2019. 5Data on file.
Impact of Growth Hormone
Distribution ADIPOSE TISSUE hGH directly stimulates the breakdown of fat1 BONE Optimal growth achieved via direct stimulation of GH receptors in bone and through IGF-11 TransCon hGH is designed to release hGH to achieve the same tissue distribution
and receptor activation in the body as daily hGH, with once-weekly administration 1Kaplan SA, Cohen P. J Clin Endocrinol Metab. 2007;92(12):4529-4535.
Adult GHD Global Phase 3 ForesiGHt
Trial Design Primary Objective: Demonstrate efficacy compared to placebo Endpoints Primary: Change from baseline in trunk % fat at 38 weeks Secondary: Change from baseline in trunk fat mass (kg) and total body lean mass (kg) at 38 weeks Exploratory:
Total body fat mass, trunk lean mass, visceral adipose tissue, total body bone mineral content and density, TRIM-AGHD, PGIS, and EQ-5D-5L scores Safety: AEs, labs, vital signs, anti-drug antibodies, ECGs, fundoscopy PK/PD: hGH, lonapegsomatropin,
mPEG, IGF-1, IGFBP-3 Key Eligibility Criteria for Main Period Enrollment (All Regions) Adults and older adults with AGHD Ages 23 - 75 years GH treatment-na ve or no GH therapy in past 12 months IGF-1 SDS -1.0 at screening Global:
Europe, North America, Asia (including Japan and China*) ~ 80 Once-weekly TransCon hGH Once-weekly TransCon hGH ~ 80 Once-weekly Placebo Once-weekly Placebo ~ 80 Daily hGH Daily hGH Dose titration (12 weeks) Target maintenance dose (26 weeks)
Once-weekly TransCon hGH Once-weekly TransCon hGH Once-weekly TransCon hGH Open-Label Extension period (52 weeks) Primary comparison for main period (double-blind for main period) Open label Main period (38 weeks): 1:1:1 randomization Once-weekly
TransCon hGH Japan only: Patients previously treated with commercially available daily hGH All regions *Conducted by VISEN Pharmaceuticals.
TransCon hGH: New Paradigm for
Growth Hormone Treatment *Conducted by VISEN Pharmaceuticals. In the phase 3 heiGHt Trial, TransCon hGH demonstrated superior AHV (P = 0.009) with a comparable safety and tolerability profile compared to a daily hGH1 In pediatric GHD, submitted BLA
June 2020 and MAA September 2020 (including Auto-Injector): FDA mid-cycle call held in December 2020, no advisory committee expected, PDUFA June 25, 2021 EMA MAA process and review underway, day 120 questions expected end of January Received orphan
designation in United States and Europe for GHD PIP approved for children from 6 months to less than 18 years Global reach and label expansion: China: Pediatric GHD phase 3 ongoing* Japan: Pediatric GHD phase 3 riGHt Trial, Clinical
Trial Notification (CTN) filed Q3 2020 Adult GHD: Ongoing global phase 3 foresiGHt Trial, complete enrollment expected by late 2021 or early 2022 Commercial manufacturing ongoing Multiple independent patent filings to provide potential IP protection
into 2039 1Thornton P, et al. Oral presentation at ENDO 2019.
TransCon PTH: PTH Replacement
Therapy for Hypoparathyroidism All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.
Hypoparathyroidism 1 Nat Rev Dis
Primers 2017 Aug 31;3:17055 2Ascendis Pharma HP Patient Experience Research. 3Endo Pract. 2014, 20(7);671-679. 4 J Bone Miner Res 2013, 28: 2570-2576; 5J Clin Endocrinol Metab 2012, 97(12): 4507-4514. 6J Bone Miner Res 2013, 28:
2277-2285. Hypocalcemia Paresthesias, muscle cramps, tetany, laryngospasm, seizures, coma 85% Report inability to perform household activities Brain fog 76% Either unable to work or report significant interference with work due to HP
symptoms Anxiety due to "fear of crash" Hypercalcemia Nocturia, polyuria, constipation, muscle weakness, coma Short-term Symptoms1 Long-term Complications4-6 4-fold Increased risk of renal disease
(nephrocalcinosis, nephrosclerosis, kidney stones & renal insufficiency) 2-fold Increased risk of depression or bipolar disorder 4-fold Increased risk of seizures 79% Require hospitalizations or emergency department
visits Patient Burden2,3
~86k - 223k 2013, Underbjerg
et. al., Cardiovascular and Renal Complications to Postsurgical Hypoparathyroidism: A Danish Nationwide Controlled Historic Follow-up Study 2015, The Epidemiology of Nonsurgical Hypoparathyroidism in Denmark: A Nationwide Case Finding Study 2016,
Astor et. al., Epidemiology and Health-Related Quality of Life in Hypoparathyroidism in Norway Europe Chronic Hypoparathyroidism: Significant Patient Population ~70k - 112k 2013, Powers et. al., Prevalence and Incidence of Hypoparathyroidism
in the United States Using a Large Claims Database, JBMR 2011, Clarke et. al., Co-morbid Medical Conditions Associated with Prevalent Hypoparathyroidism: A Population-Based Study Estimated Prevalence: ~200k in these 4 regions USA ~12k - 13k S.
Korean ICD-10 codes Ascendis market research South Korea ~25k - 32k 2017. Shishiba et. al., Prevalence of postsurgical hypoparathyroidism in Japan: Estimated from the data of multiple institutes 1999. Nakamura et. al., Prevalence of
Idiopathic Hypoparathyroidism and Pseudohypoparathyroidism in Japan Ascendis market research Japan
TransCon PTH Phase 2 Trial Design
PRO = Patient-reported Outcome. HPES = Hypoparathyroidism Patient Experience Scale. BMD = Bone Mineral Density. TBS =Trabecular Bone Score. DXA = Dual-Energy X-Ray Absorptiometry. FECa = Fractional Excretion of Calcium. 59 adult subjects with HP
currently receiving standard of care (active vitamin D + calcium); 1:1:1:1 randomization Primary Composite Endpoint (4 weeks) Proportion of subjects with: Normal serum calcium; and Normal FECa (or at least 50% decrease from baseline); and Off active
vitamin D; and Taking 1,000 mg/day calcium Double-Blinded Treatment (4 weeks) RANDOMIZATION Screening 4 weeks Open-Label Extension (OLE) TransCon PTH Individual Dosing (6 - 30 g/day) TransCon PTH Titration & SoC
Optimization Individualized Dosing TransCon PTH 15 g/day TransCon PTH 18 g/day TransCon PTH 21 g/day Placebo Key Secondary Endpoints (4 weeks) Primary composite and taking 500 mg/day calcium Additional Endpoints 4
weeks PRO measures (including HPES and SF-36) Nephrolithiasis, nephrocalcinosis, vascular calcification, ER/urgent care visits and hospitalizations BMD and TBS by DXA, bone turnover markers, 24-hour urine calcium excretion (in extension only) ALL
Preliminary PaTH Forward OLE Safety
Summary TransCon PTH was generally well-tolerated 58 out of 59 randomized subjects currently receiving TransCon PTH in OLE* No drug-related serious TEAEs were reported No TEAEs leading to discontinuation of study drug TEAEs with TransCon PTH reflect
known PTH pharmacology Injections were well-tolerated using pen injector planned for commercial presentation No new safety signals identified in the OLE portion of the study *As of January 5, 2021. Preliminary PaTH Forward OLE 6-month data. TEAE =
Treatment emergent adverse event No subjects had PTH TEAEs related to hyper- or hypocalcemia leading to ER/urgent care visit and/or hospitalization
OLE starts PaTH Forward OLE Mean
Active Vitamin D Dose TransCon PTH enabled discontinuation of active vitamin D within two weeks of treatment initiation Preliminary PaTH Forward OLE 6-month data. Data on file. Mean Active Vitamin D Dose g/day ( SE) Weeks
OLE starts PaTH Forward OLE Mean
Calcium Supplement Dose TransCon PTH enabled rapid and continuous calcium supplement reduction over 6-month study period Preliminary PaTH Forward OLE 6-month data. Data on file. Mean Calcium Dose mg/day ( SE) Weeks
Mean Calcium Corrected for Albumin
mg/dL ( SE) PaTH Forward OLE Mean Serum Calcium and Mean 24-Hour Urine Calcium Preliminary PaTH Forward OLE 6-month data. Data on file. ULN = Upper limit of normal. Mean 24-hour Urine Calcium mg/24hr ULN (men) ULN (women) Mean 24-hour urine
calcium normalized while maintaining normal mean serum calcium Mean Serum Calcium Mean 24-hour Urine Calcium Normal range Weeks (N = 36) (N = 8) (N = 44)
PaTH Forward OLE Change in
SF-36 Health Survey Domain Mean Scores (SD) Preliminary PaTH Forward OLE 6-month data. Data on file. Green: Means above lower limit of population norm (47). (SD). *PF (physical functioning), RP (role physical), BP (bodily pain), GH (general
health), VT (vitality), SF (social functioning), RE (role emotional), MH (mental health), PCS (physical component summary), MCS (mental component summary). Placebo (N = 15) Placebo Switch to TransCon PTH (N = 15) TransCon PTH (N =
44) All TransCon PTH (N = 59) SF-36 Domain* Baseline Week 4 6 Months Baseline Week 4 6 Months Baseline 6 Months PF 45 (11) 46 (14) 51 (7) 46 (9) 51 (6) 52 (5) 46 (10) 51 (6) RP 42 (10) 42 (14) 49 (11) 42 (10) 49 (8) 51 (6) 42 (10) 50 (7) BP 43
(11) 40 (16) 46 (10) 46 (10) 49 (8) 51 (9) 45 (10) 50 (9) GH 44 (10) 47 (11) 50 (7) 43 (10) 47 (8) 51 (9) 43 (10) 51 (8) VT 44 (12) 43 (12) 52 (10) 42 (11) 49 (9) 53 (8) 43 (11) 53 (8) SF 44 (11) 41 (15) 53 (5) 42 (10) 50 (8) 52 (6) 43 (10) 52 (6)
RE 45 (12) 39 (16) 51 (7) 42 (13) 49 (10) 50 (8) 43 (13) 50 (7) MH 47 (9) 47 (11) 55 (5) 46 (9) 51 (8) 51 (8) 46 (9) 52 (7) PCS 43 (12) 44 (14) 48 (8) 45 (10) 49 (7) 51 (7) 44 (11) 50 (8) MCS 46 (10) 43 (12) 54 (6) 43 (11) 50 (9) 51 (8) 44 (11) 52
OLE starts OLE starts PaTH Forward