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Cautionary Note On Forward-Looking Statements This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, such as statements regarding o

Key Takeaway: Ascendis Pharma A/S January 2020 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 oper

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Ascendis Pharma A/S January 2020
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, timing and likelihood of success, plans and objectives of management for future
operations, and future results of current and anticipated products, 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, 2019 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 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 2020 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 Endocrinology rare disease internal pipeline and expected 2020 milestones TransCon hGH for pediatric GH deficiency: BLA
and MAA filings expected Q2 and Q4 TransCon PTH for hypoparathyroidism: Phase 2 top-line data end March1; long-term data Q3 TransCon CNP for achondroplasia: Phase 2 ACcomplisH dose escalation and initiate second trial in China2 Q4 Build leading
positions for each endocrinology rare disease product with commercial focus on maximizing global reach Partnership with VISEN Pharmaceuticals for endocrinology rare disease products in China Oncology pipeline in development with highly
differentiated product candidates First IND filing or equivalent expected in 2020 As of September 30, 2019, cash and cash equivalents of ~ 659 million 1 Results timing +/- two weeks; 2Through VISEN Pharmaceuticals
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 Growth Hormone for pediatric growth hormone deficiency TransCon PTH
for adult hypoparathyroidism TransCon CNP for achondroplasia Create further growth of 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 In Oncology, create a high value pipeline with one IND or equivalent filing each year Creation of a third independent therapeutic area with a diversified pipeline
Diverse Pipeline of Independent Product
Candidates 1 Excludes rights granted to VISEN Pharmaceuticals in Greater China 2 In phase 3 development for pediatric growth hormone deficiency in Greater China through strategic investment in VISEN Pharmaceuticals
Transient Conjugation: Flexible and
Versatile Platform Parent Drug Soluble Carriers Insoluble Carriers Antibodies, Antibody Fragments, Proteins, Peptides and Small Molecules Aromatic Cyclic Imide DKP Carbamate Bicin AEG Pyroglutamate TransCon Carrier TransCon Prodrug: 3 components
TransCon Technology: Sustained Systemic
Delivery Parent drug is transiently bound to a TransCon linker-soluble carrier moiety, which inactivates and shields parent drug from clearance Designed to distribute released drug like the parent molecule; linker-carrier is cleared renally
Following injection, the linker is designed to autocleave at a specific rate to predictably release unmodified parent drug TransCon carrier TransCon linker Parent drug (inactive) Unmodified parent drug Receptor Linker cleavage dependent upon pH and
temperature Renal clearance Prodrug (inactive)
Parent drug is transiently bound to
TransCon linker-hydrogel carrier, which inactivates, shields parent drug and prevents clearance Designed to provide sustained high local drug levels with low systemic exposure; hydrogel degrades into small polymers that are renally cleared Following
injection, the linker is designed to autocleave at a specific rate to predictably release unmodified parent drug TransCon Technology: Sustained Localized Delivery Linker cleavage dependent on pH and temperature Parent drug (inactive) Unmodified
parent drug TransCon hydrogel carrier Receptor Renal clearance TransCon linker Prodrug (inactive)
Ascendis Algorithm for Product
Innovation Unmet Medical Need Clinically Validated Parent Drug TransCon Technology Suitability Clearly Differentiated Product Established Clinical & Regulatory Pathway Large Addressable Market Higher Value, Lower Risk Pipeline
TransCon Growth Hormone: Once-Weekly
Growth Hormone Supports Overall
Endocrine Health Sources: 1. de Boer, H. et al. 1997; 2. Rutherford, O. M. et al. 1991. 3. Colle, M., J. Auzerie.1993. 4. Johannsson, Gudmundur, et al. 1999. 5. Stabler, Brian et al. 1996. 6. Leong, Gary M., Gudmundur Johannsson. 2003. 7. Colao,
Annamaria et al. 2002. 8. Bex, M, and R Bouillon. 2003 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 fully mimic daily hGH to adequately address the totality of the disease
TransCon hGH Design TransCon carrier
TransCon linker hGH (inactive) Unmodified hGH Receptor Linker cleavage dependent upon pH and temperature Renal clearance Once-weekly prodrug releases unmodified hGH designed to mimic daily hGH: Tissue distribution Physiological levels Therapeutic
effects: efficacy, safety and tolerability
Growth Comparable to a Daily hGH in
Phase 21,2 1 Intergroup differences not statistically significant 2 J Clin Endocrinol Metab 2017, 102(5): 1673-1682 3 Conducted with a bioequivalent version of TransCon hGH Same weekly dose Dose hGH (mg/kg/week): 11.5 0.14 0.21 0.30 0.21
TransCon hGH3 Genotropin 26-week treatment period (N=53)
TransCon hGH Phase 3 Program in
Pediatric GHD Subjects previously treated (n=143) and treatment-na ve (<3 years, n=3) Extension trial (N=296) Expected Regulatory filings (BLA Q2 2020, MAA Q4 2020) Treatment-na ve subjects N=146 N=161
Phase 3 heiGHt Trial 161
treatment-na ve children with GHD dosed (2:1 randomization) TransCon hGH (0.24 mg/kg/week) Genotropin (34 g/kg/day = 0.24 mg/kg/week) Long-Term Extension Trial Week 1 Week 5 Week 13 Week 52 Week 26 Week 39 Screening 6 weeks Key
Endpoints Annualized height velocity (AHV) at 52 weeks (primary endpoint) AHV at earlier time points Change in height SDS over 52 weeks Change in serum IGF-1/IGFBP-3 levels Change in IGF-1 SDS and IGFBP 3 SDS Normalization of IGF-1 SDS hGH and
IGF-1 levels over 168 hours at Week 13 (PK/PD subset) VISIT SCHEDULE Objective Demonstrate non-inferiority Key Inclusion Criteria Prepubertal children with GHD Height SDS -2.0 IGF-1 SDS -1.0 2 GH stimulation tests (GH 10 ng/mL)
Bone age 6 months behind chronological
Demographics and Baseline
Characteristics Comparable Between Arms TransCon hGH (n=105) Mean Genotropin (n=56) Mean Age (years) 8.51 8.48 Male (%) 81.9 82.1 Height SDS -2.89 -3.00 Average Parental Height SDS -2.32 -2.55 IGF-1 SDS -2.08 -1.96 Peak Stimulated GH (ng/mL)
5.89 5.48 BMI (kg/m2) 16.1 16.5 BMI SDS -0.32 -0.14 Bone Age (years) 5.84 5.98 Bone Age-to-Chronologic Age (BA/CA) 0.69 0.70 Caucasian (%) 95.2 92.9
TransCon hGH Met Primary Objective
of Non-inferiority and Demonstrated Superiority in AHV at Week 52 TransCon hGH 0.24 mg/kg/week (n=105) Genotropin 0.24 mg/kg/week (n=56) Estimate of Treatment Difference P-value LS Mean AHV at Week 52 (cm/year) 11.2 10.3 0.86 0.0088 Standard
Error 0.23 0.30 0.33 95% Confidence Interval (cm/year) 10.71 - 11.62 9.73 - 10.89 0.22 - 1.50 ANCOVA model was applied after missing data were imputed by multiple imputation method.
AHV Consistently Favors TransCon hGH
Across All Subgroups at Week 52 Treatment Difference (TransCon hGH - Genotropin) cm/year ANCOVA Model Age < 6 years 24% 25% 6 years 76% 75% Sex Male 82% 82% Female 18% 18% Baseline GH-Stimulation 5ng/mL 35% 38% > 5 ng/mL
65% 63% Etiology and Extent of GHD Isolated Idiopathic 65% 66% Isolated Organic 18% 16% Multiple Pituitary Hormone Deficiency 17% 18% Overall Favors Genotropin Favors TransCon hGH TransCon hGH (n=105) Genotropin (n=56)
AHV Poor Responders: Post-hoc
Analysis Poor responders defined as AHV <8.0 cm/year1 1 Bakker et. al. J Clin Endocrinol Metab 93: 352-357, 2008 2 Excludes one subject per group with missing Week 52 data (98.8% subjects completed study) At Week 522 TransCon hGH (n=104) n
(%) Genotropin (n=55) n (%) Responder 100 (96.2) 49 (89.1) Poor Responder 4 (3.8) 6 (10.9) Incidence of poor responders ~3x lower in TransCon hGH arm compared to daily Genotropin arm
IGF-1 Profile Over 1 Week TransCon
hGH (0.24 mg/kg/week) (n=11) Days (Week 13) 1 2 3 0 5 4 7 6 Baseline 13th Dose Mean SDS ( SE)
AHV Paralleled the Difference in
Average IGF-1 Baseline Week 13 Week 26 Week 39 Week 52 -5 -4 -3 -2 -1 0 1 2 3 4 Model-derived Average IGF-1 SDS IGF-1 SDS AHV* (cm/year) LS Mean AHV ( SE) TransCon hGH Genotropin TransCon hGH preserved the balance between direct and indirect
effects of daily hGH P-value=0.0088 11.2 10.3 *ANCOVA model
Phase 3 fliGHt Trial Design 1
Primary outcome measure was safety and tolerability of TransCon hGH over 26 weeks 146 children with GHD (143 treatment-experienced) TransCon hGH (0.24 mg/kg/week) Long-Term Extension Trial Week 1 Week 4* ( 1 Week) Week 26 ( 1 Week) Week 13
( 1 Week) Screening Up to 4 Weeks VISIT SCHEDULE * Visit for <3 year olds only Key Endpoints1 Adverse events Injection site reactions Incidence of anti-hGH antibodies Annualized height velocity (AHV) Change in height SDS Proportion of
subjects with IGF-1 SDS (0.0 to +2.0) PK/PD in subjects <3 years Preference and satisfaction with TransCon hGH Key Inclusion Criteria Investigator-determined GHD with supporting biochemical and auxologic criteria Age 6 months - 17 years old
Tanner stage <5 Open epiphyses Treated with commercially-available daily hGH therapy 0.20 mg/kg/week for 13 - 130 weeks Children <3 years could have been treatment-na ve
fliGHt Baseline Demographics
Top-line results from phase 3 fliGHt Trial. Baseline Mean (N=146) Male (%) 75.3 Age (years) 10.6 Age Range (years) 1 to 17 Height SDS -1.42 BMI (kg/m2) 17.5 Average Parental Height SDS -1.14 IGF-1 SDS +0.9 IGF-1 SDS Range -1.9 to +4.0
Caucasian (%) 84.9 Recruited in North America (%) 95.2
Previous Daily hGH Use Top-line
results from phase 3 fliGHt Trial. Baseline (N=146) Daily hGH Dose Prior to Trial (mg/kg/week), mean (range) 0.29 (0.13 - 0.49) Treatment-Experienced, n (%) 143 (97.9%) <6 Months 40 (27.4%) 6 to <12 Months 32 (21.9%) 12 to
<18 Months 28 (19.2%) 18 Months 43 (29.5%) Treatment-Na ve, n (%) 3 (2.1%)
Mean AHV at Week 26 by Subgroups
Top-line results from phase 3 fliGHt Trial. AHV at Week 26 (cm/year) TransCon hGH (N=146) Arithmetic Mean Age <3 years 16.2 3 and <6 years 10.0 6 and <11 for girls; 6 and <12 for boys 8.2 11 for girls;
12 for boys 9.0 Gender Male 9.0 Female 9.1 Peak Stimulated GH 5 ng/mL 9.6 >5 ng/mL 8.6
Key Learnings from TransCon hGH
Clinical Trials TransCon hGH demonstrated an adverse event and immunogenicity profile comparable to that of a daily hGH TransCon hGH demonstrated superior height velocity1 to a daily hGH through a PK profile of released hGH that may be more
efficiently utilized by target tissues TransCon hGH data showed predictable linear response to dose titrations TransCon hGH data suggest the same mode of action as daily hGH and preservation of the biological balance between direct hGH and IGF-1
effects in target tissues 1 Based on results from phase 3 heiGHt Trial at 52 week endpoint
Adverse Event Profile of TransCon
hGH in the Phase 3 Program1 heiGHt Trial fliGHt Trial enliGHten Trial2 TransCon hGH 0.24 (n=105) n (%) Genotropin 0.24 (n=56) n (%) TransCon hGH 0.24 (N=146) n (%) TransCon hGH 0.24 (N=296) n (%) Treatment-emergent Adverse Events (TEAEs) 81 (77) 39
(70) 83 (57) 161 (54) TEAEs Related to Study Drug 12 (11) 10 (18) 6 (4.1) 10 (3.4) Serious Adverse Events (SAEs) 1 (1.0) 1 (1.8) 1 (0.7)3 5 (1.7)4 SAEs Related to Study Drug 0 0 0 0 TEAEs Leading to Any Action on Study Drug 2 (1.9) 1 (1.8) 2 (1.4) 5
(1.7) TEAEs Leading to Discontinuation of Study Drug 0 0 0 0 1 All doses expressed in mg/kg/week 2 Based on data reported up to September 2019 3 One subject reported two SAEs; both considered unrelated to study drug 4 Two subjects reported two SAEs;
all considered unrelated to study drug TransCon hGH had an adverse event profile comparable to daily hGH which was consistent across phase 3 trials
TransCon hGH Sustained Improvement
in Height SDS Change from Baseline LS Mean (+SE) heiGHt Trial subjects rolled over into enliGHten Trial (long-term extension) 1 Based on results from phase 3 heiGHt Trial at 52 week endpoint *Treatment difference resulted in a nominal p-value
<0.05 ANCOVA model heiGHt subjects treated for 1.5 years with TransCon hGH demonstrated: Superior growth after 52 weeks compared to Genotropin1 Superior growth continued in the enliGHten extension trial
Linear Relationship Between Dose and
IGF-1 Response Demonstrated in Clinical Program 1 Average IGF-1 at Week 13 was used given availability of measured data over one week for the phase 2 trial 2 Average IGF-1 during Week 13 for phase 3 heiGHt Trial TransCon hGH subjects is
Last updated: Jan 13, 2020