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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 2019 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 2019
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 March 28, 2018, 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 2019 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 Unique algorithm for product innovation has resulted in successful clinical validation of 3 out of 3 product candidates
within the endocrinology rare disease area Endocrinology rare disease internal pipeline and expected near-term milestones TransCon hGH for pediatric GH deficiency: Phase 3 heiGHt Trial top-line data Q1 2019 TransCon PTH for hypoparathyroidism: Phase
2 top-line data Q4 2019 TransCon CNP for achondroplasia: Phase 2 initiation Q3 2019 Build leading positions for each endocrinology rare disease product with commercial focus on the U.S. and select European markets VISEN Pharmaceuticals for
commercialization of endocrinology rare disease products in China Established high-value collaborations with Roche/Genentech in ophthalmology and Sanofi in diabetes As of September 30, 2018, cash and cash equivalents of 310.3
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 parent drug like the endogenous compound; linker-carrier is cleared renally
Following injection, the linker is designed to autohydrolyze at specific rates to predictably release unmodified parent drug TransCon carrier TransCon linker Inactive parent drug Unmodified parent drug Receptor Linker cleavage dependent upon pH and
temperature Renal clearance
TransCon Technology: Sustained
Localized Delivery 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 drug release Following injection, the linker is designed to autohydrolyze at specific rates to predictably release unmodified parent drug Linker cleavage dependent on pH and temperature Inactive
parent drug Unmodified parent drug TransCon Hydrogel carrier Receptor Renal clearance TransCon linker
Sustained Localized Delivery: Validated
Across Multiple Drugs and Administration Sites Vitreal PK of Fab following intra-vitreous administration in rabbits. TransCon Fab half-life was ~53 days compared to free Fab half-life of ~3.2 days. Plasma PK of Daptomycin following intra-articular
administration in rabbits. TransCon Daptomycin half-life was ~3 days. Excellent local tolerability of TransCon hydrogel carrier Sustained high local concentration with low systemic exposure Small Molecules Intra-articular administration Antibody
Fragments (Fab) Intra-vitreous administration1 Fab Concentration ( g/mL) Time (day) 0 20 40 60 1 10 100 1000 Free Fab TransCon Fab 1 Patent WO2018175788 1000 100 10 1 0 2 4 6 8 10 12 14 TransCon Daptomycin Time (day) Daptomycin (ng/mL)
Ascendis Algorithm for Product
Innovation Our unique algorithm for product innovation has resulted in clinical validation of 3 out of 3 product candidates in Endocrinology Rare Disease 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
PRODUCT CANDIDATE PRIMARY INDICATION
DEVELOPMENT STAGE POTENTIAL WW MARKET1 WW COMMERCIAL RIGHTS TransCon Anti-VEGF Ophthalmology Not disclosed >$7 billion TransCon Peptides Diabetes Not disclosed >$1 billion PRODUCT CANDIDATE PRECLINICAL PHASE 1 PHASE 2 PHASE 3 POTENTIAL WW
MARKET1 COMMERCIAL RIGHTS2 TransCon hGH > $3 billion3 TransCon PTH > $2 billion4 TransCon CNP > $1 billion Building a Leading Company in Rare Diseases Internal Endocrinology Pipeline Hypoparathyroidism Pediatric Growth Hormone Deficiency
Achondroplasia 1 Based on market data and Company estimates 2 Excludes rights granted to VISEN Pharmaceuticals in Greater China 3 Includes all indications 4 Based on treatment of ~25% of the U.S. patient population of ~80,000 patients Strategic
Collaborations Adult Growth Hormone Deficiency
TransCon Growth Hormone: Once-Weekly
Well-established market primed for
disruption by a long-acting growth hormone product The Growth Hormone Market1 ~$3.5 billion in worldwide rhGH2 sales and growing (2.4% CAGR)3 Fragmented market with same undifferentiated hGH molecule competing on differentiated formulations,
devices, services and access strategies Pediatric indications comprise ~90% of the market Indications for growth hormone treatment include: Growth Hormone Deficiency (GHD) ~50% of market Turner syndrome Idiopathic short stature (ISS) Prader-Willi
syndrome Small for gestational age (SGA) 1 Based on company research 2 Recombinant human growth hormone; subsequently referred to in this presentation as hGH 3 Compounded Annual Rate of Growth based on 2010-2014 data
Clinical Implications of Untreated
GHD 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 Fractures Adult peak bone mass is considerably lower, and rates of fractures are significantly higher among adults with GHD who were not treated as children.8 Ultimate Height Achievement Adults who had
child-onset GHD may not achieve full height potential if treatment is stopped prior to adulthood.1 Cardiovascular Disease Early discontinuation of GH treatment may induce impairment of patients' lipid profiles and cardiac structure and
performance, leading to increased risk for CV disease.6,7 Mental Health A high incidence of psychiatric disorders, usually accompanied by poor life quality, is associated with adults who were GHD as children.5 Body Composition Increased fat mass,
decreased muscle mass, and decreased bone density have been shown to occur soon after treatment discontinuation.2,3,4 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
Increased adherence Improved growth
Doses missed per week1 3 2 p< 0.001 p< 0.01 4 3 2 1 0 1 Height velocity SDS Poor adherence with daily hGH therapy is associated with reduced height velocity and impaired quality of life1 Daily Growth Hormone: The Problem 1 PLoS
ONE 2011, 6(1): e16223 2 Clinical Therapeutics 2008, 30(2): 307-316 Reduced frequency of administration is associated with better adherence2 In the 1st year, two of three patients miss >1 injection on average per week1
TransCon hGH Design Once-weekly
prodrug releases unmodified hGH designed to mimic daily hGH: Tissue distribution Physiological levels Therapeutic effects: efficacy, safety and tolerability TransCon carrier TransCon linker Inactive parent drug Unmodified parent drug Receptor Linker
cleavage dependent upon pH and temperature Renal clearance
Efficacy Safety (including
immunogenicity) Tolerability TransCon Growth Hormone Target Product Profile Comparable to Daily Growth Hormone Weekly subcutaneous administration Small injection volume (31G needle) Room temperature storage Device Easy to use Automatic data capture
Growth Comparable to a Daily hGH in
Phase 21,2 Same weekly dose 11.5 14.5 0.14 mg 0.21 mg 0.30 mg 0.21 mg Dose (GH/kg/week): 1 Intergroup differences not statistically significant 2 J Clin Endocrinol Metab 2017, 102(5): 1673-1682 3 Conducted with a previous lower strength
version of TransCon Growth Hormone 26-week treatment period Thorough PK/PD assessments at weeks 1 and 13 TransCon Growth Hormone3 Genotropin
Dose Proportional IGF-1 Response in
Phase 21 Days (Week 13) IGF-1 SDS (+ SEM) 0 1 2 3 4 5 6 7 Transient values greater than +2.0 observed in a small number of patients primarily at the highest dose level 1 J Clin Endocrinol Metab 2017, 102(5): 1673-1682
Comparable hGH Levels in Phase 21
Maximum hGH concentration comparable between equivalent weekly doses of TransCon hGH and a daily hGH Days (Week 13) hGH serum concentration (+SEM, ng/ml) 1 J Clin Endocrinol Metab 2017, 102(5): 1673-1682
Comparable Safety to a Daily hGH in
Phase 21 >1100 TransCon hGH injections administered No reports of lipoatrophy or nodule formation No serious adverse events related to study drug Immunogenic profile comparable to a daily hGH Injection site tolerability comparable to a daily hGH
Adverse events consistent with daily hGH therapy observed and not different between cohorts No occurrence of neutralizing antibodies Low incidence of low-titer non-neutralizing antibodies 1 J Clin Endocrinol Metab 2017, 102(5):
TransCon hGH Phase 3 Program FDA and
EMA support size and scope of program for pediatric GHD filing Database lock for filing package expected Q3 2019 Switch trial (n=146) Fully enrolled Data expected Q2 2019 Extension trial (n~300) Regulatory Filings Pivotal trial (n=161) Fully
enrolled Data expected Q1 2019 Ongoing
Phase 3 heiGHt Trial Ongoing 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 TransCon hGH (0.24 mg/kg/week) Genotropin (34 g/kg/d =
0.24 mg/kg/week) Key Endpoints Annualized height velocity at 52 weeks (primary endpoint) Annualized HV at earlier time points Change in HT 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 Long-Term Extension Trial Week 1 Week 5 Week 13 Week 52 Week 26 Week 39 161 treatment-na ve children with GHD dosed (2:1 randomization) VISIT SCHEDULE Screening 6 weeks
Phase 3 heiGHt Trial Update1 161
subjects enrolled 1 discontinued from treatment after unrelated appendectomy 100% of subjects who completed heiGHt Trial enrolled in enliGHten Trial Observed data from the heiGHt Trial continue to indicate a safety profile consistent with the
published safety profile for daily hGH TransCon hGH (0.24 mg/kg/week) Genotropin (34 g/kg/d = 0.24 mg/kg/week) Long-Term Extension Trial Week 1 Week 5 Week 13 Week 52 Week 26 Week 39 161 treatment-na ve children with GHD dosed (2:1
randomization) VISIT SCHEDULE Screening 6 weeks 1 As of January 3, 2019
heiGHt Trial: Baseline Demographics
and Model Prediction for Daily Arm Sponsor Versartis LG Life Sciences Biopartners Daily hGH cohort Genotropin Genotropin Valtropin Humatrope Dose of daily hGH 0.034 mg/kg/d 0.030 mg/kg/d 0.030 mg/kg/d 0.030 mg/kg/d (0.24 mg/kg/wk) (0.21 mg/kg/wk)
(0.21 mg/kg/wk) (0.21 mg/kg/wk) Subjects 32 87 98 49 Mean age, yr 7.03 7.80 8.10 8.50 Gender, male % 68.7 63.2 70.4 61.2 Mean bone age, yr 5.29 4.29a 5.14 5.50 Mean bone age delay, yr 1.74 3.51 2.96 3.00 Mean peak GH, g/L 5.87 1.98 3.60b 4.90b
Mean height SDS -2.64 -4.36 -3.53c -3.24d Mean IGF-1 SDS -1.87 -4.30 NA NA Annualized HV, cm/yr (observed in daily cohort) 10.7 12.0 11.3 10.5 aDerived from BA/CA. bClonidine test only. cAverage based on -3.54 (n=88) and -3.52 (n=99). dBased on
n=50. eTotal study N used because of blinding fPredicted mean HV using a formula based on the Ranke model: HVHeiGHt = HVx - 1.37ln(peak GHHeiGHt/peak GHx) - 0.32(AgeHeiGHt - Agex) + 1.62*ln(DoseHeiGHt/Dosex); Ranke, M.B., J Clin
Endocrinol Metab, 1999. 84(4): p. 1174-83 10.3-10.7f Demographic data from the daily hGH arm of 12-month phase 3 pediatric GHD trials Model-predicted annualized HV of Genotropin arm in heiGHt Trial Ascendis Pharma Genotropin 0.034 mg/kg/d (0.24
mg/kg/wk) 161e 8.50 82.0 5.87 2.63 5.77 -2.93 -2.04
Auto-Injector Designed to Improve
Adherence Auto-injector introduction during extension study and for commercial launch Simple operation with few user steps Single low-volume (<0.60 mL) injection for patients 60kg Small needle, comparable to daily hGH (31G, 4mm) Room
temperature storage No waste due to empty-all design Bluetooth connectivity enabled for automatic data capture Device lifetime at least 4 years Key Features
Improve Adherence Through Feedback
& Intervention Secure Cloud-Based Central Database Integrating with a Connected Healthcare Platform Automated Data Capture of Dose and Injection Time TransCon hGH Auto-Injector Data Analysis
TransCon hGH: Highlights Potential
best-in and first-in-class long-acting hGH in pediatric GHD Trial phase 3 top-line data expected Q1 2019 Trial top-line data expected Q2 2019 Introduction of auto-injector into Trial expected Q2 2019 Clinical database lock for filing package
expected Q3 2019 Improving adherence through integrated automatic data capture and connected healthcare system Commercial-scale manufacturing and supply chain established Multiple patent filings provide potential protection, with auto-injector, into
TransCon PTH: PTH Replacement
Therapy for Hypoparathyroidism
Hypoparathyroidism: Serious Unmet
Medical Need Parathyroid hormone (PTH) regulates calcium/phosphate homeostasis Hypoparathyroidism (HP) is a rare disease characterized by deficient or absent PTH Low serum calcium, increased serum phosphate and urine calcium levels Most common cause
(~75%) is inadvertent removal or damage to parathyroid glands during thyroid surgery Approximately 80,000 patients in the U.S. HP results in diverse physical, cognitive, and emotional symptoms with high burden on the healthcare system despite
current standard of care 79% require hospitalizations or emergency department visits 4-fold increased risk of renal disease (calcifications and renal insufficiency) Sources: J Bone Miner Res 2013, 28: 2570-2576; J Clin Endocrinol Metab 2012, 97(12):
Last updated: Jan 7, 2019