Ascendis Pharma A/s · NASDAQ:ASND
Ascendis Pharma A/s — Investor Presentation (January 2018)
50 slides from Ascendis Pharma A/s's investor presentation, Jan 8, 2018
Slide 1: Ascendis Pharma A/S January 2018
Ascendis Pharma A/S January 2018 Exhibit 99.1
Slide 2: Cautionary Note On Forward-Looking Statements
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
Slide 3: Company Overview
Company Overview Create best-in-class rare disease products addressing unmet medical needs Apply TransCon technology to parent drugs with clinical proof-of-concept Expect higher development success rate compared to traditional drug development Endocrinology rare disease internal pipeline and expecte
Slide 4: TransCon Technology Overview
TransCon Technology Overview Parent drug is protected from receptor activation and clearance by transiently binding to the linker-carrier Parent drug distribution as original compound; Linker-carrier elimination mainly by renal clearance Following injection, the TransCon linker slowly autohydrolyzes
Slide 5: Ascendis Approach to Product Innovation
Ascendis Approach to Product Innovation 1 Totals from FDA and EMA Orphan List, public & proprietary databases, advisors and conferences Unmet Medical Need Clinically Validated Parent Drug TransCon Technology Suitability Clearly Differentiated Product Established Clinical & Regulatory Pathway Large A
Slide 6: Building a Leading Company in Rare Diseases
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 PRE IND PHASE 1 PHASE 2 PHASE 3 POTENTIAL WW MARKET1 WW COMMERCIAL RIGHTS
Slide 7: TransCon Growth Hormone: Once-Weekly Replacement Therapy
TransCon Growth Hormone: Once-Weekly Replacement Therapy
Slide 8: Well established market primed for disruption by a long-acting growth hormone product
Well established market primed for disruption by a long-acting growth hormone product The Growth Hormone Market1 ~$3.5 billion in worldwide daily hGH sales and growing (2.4% CAGR) Fragmented market with same undifferentiated hGH molecule competing on differentiated formulations, devices, services an
Slide 9: Growth Hormone Deficiency: Clinical Manifestations
Growth Hormone Deficiency: Clinical Manifestations 1 BMC Endocrine Disorders 2012, 12:26 2 J Clin Endocrinol Metab 2006, 91: 1621–1634 Long-acting GH must fully mimic daily hGH to address the totality of the disease PEDIATRIC Growth Hormone Deficiency1 Growth failure Increased and abnormal fat distr
Slide 10: Daily Growth Hormone: The Problem
Increased adherence Improved growth response Doses missed per week ≥3 2 p< 0.001 p< 0.01 4 3 2 1 0 ≤1 Height Velocity SDS Poor adherence with daily growth hormone therapy is associated with reduced height velocity and impaired quality of life1 Daily Growth Hormone: The Problem 1 PLoS ONE 2011, 6(1):
Slide 11: TransCon Growth Hormone: The Opportunity
TransCon Growth Hormone: The Opportunity Predictable release of parent drug in the body hGH hGH TransCon carrier TransCon linker Inactive Prodrug Creation of TransCon prodrug Once-weekly prodrug releasing unmodified hGH designed to mimic daily hGH: Tissue distribution Physiological levels Therapeuti
Slide 12: Growth Comparable to a Daily hGH in Phase 2
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 (hGH/kg/week): 1 Intergroup differences not statistically significant 2 JCEM, DOI: 10.1210/jc.2016-3776 3 Conducted with a previous lower strength version of TransCon Growth Hormone 26-week
Slide 13: Dose Proportional IGF-1 in Phase 2
Dose Proportional IGF-1 in Phase 21 Days (Week 13) IGF-1 SDS (+ SEM) 0 1 2 3 4 5 6 7 Transient point values of IGF-1 SDS > +2.0 have been observed in a small number of patients primarily at the highest dose level 1 JCEM, DOI: 10.1210/jc.2016-3776
Slide 14: Comparable hGH Levels in Phase 2
Comparable hGH Levels in Phase 21 Maximum hGH concentration comparable between equivalent weekly doses of TransCon Growth Hormone and a daily hGH Days (Week 13) hGH serum concentration (+SEM, ng/ml) 1 JCEM, DOI: 10.1210/jc.2016-3776
Slide 15: Comparable Safety to a Daily hGH in Phase 2
Comparable Safety to a Daily hGH in Phase 21 >1100 TransCon Growth Hormone injections administered in the phase 2 pediatric study 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 co
Slide 16: TransCon Growth Hormone Phase 3 Update
TransCon Growth Hormone Phase 3 Update FDA and EMA support size and scope of program for pediatric GHD filing Database lock for filing package Q3 2019 Switch trial Enrollment completion ~Q3 2018 Extension trial (n= ~300) Regulatory Filings Pivotal trial Fully enrolled Data expected Q1 2019 Ongoing
Slide 17: Phase 3 heiGHt Trial Ongoing
Phase 3 heiGHt Trial Ongoing Key Inclusion Criteria Prepubertal children with GHD Height SDS ≤ -2.0 IGF-1 SDS ≤-1.0 GHD with 2 GH stim. tests (GH ≤10 ng/mL) Bone age ≥ 6 months behind chronological TransCon Growth Hormone (0.24 mg/kg/week) Genotropin (34µg/kg/d = 0.24 mg/kg/week) Key Endpoints Annua
Slide 18: Auto-Injector Designed to Improve Adherence
Auto-Injector Designed to Improve Adherence Auto-injector introduction during extension study and for commercial launch Simple operation with few user steps A single low-volume (<0.60 mL) injection for patients less than 60kg Small needle, comparable to daily hGH (31G, 4mm) Room temperature storage
Slide 19: Improve Adherence Through Feedback & Intervention
Improve Adherence Through Feedback & Intervention Secure Cloud-Based Central Database TransCon hGH Auto-Injector Automated Data Capture of Dose and Injection Time Integrating with a Connected Healthcare System
Slide 20: TransCon Growth Hormone Target Product Profile
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 Empty-all design
Slide 21: TransCon Growth Hormone: Highlights
TransCon Growth Hormone: Highlights Potential best-in and first-in class long-acting growth hormone in pediatric GHD Trial phase 3 top-line results expected Q1 2019 Trial expected to be fully enrolled Q3 2018 Auto-injector developed and on-track for introduction in Trial Improving adherence through
Slide 22: TransCon PTH: Once-Daily for Hypoparathyroidism
TransCon PTH: Once-Daily for Hypoparathyroidism
Slide 23: Hypoparathyroidism: Serious Unmet Medical Need
Hypoparathyroidism: Serious Unmet Medical Need1 Parathyroid hormone (PTH) regulates calcium/phosphate homeostasis Calcium is essential for muscle, skeletal, neurological and cardiac function Hypoparathyroidism (HP) is a rare disease characterized by deficient or absent PTH Results in low calcium and
Slide 24: Hypoparathyroidism: Burden of Illness
Hypoparathyroidism: Burden of Illness Calcium multiple times daily and vitamin D is current standard of treatment Despite current treatment, study showed1: 72% of patients experienced >10 symptoms* in the preceding 12 months Symptoms were experienced for a mean of 13 ± 9 hours/day Hospital stays or
Slide 25: HP Treatment Strategies Are Evolving
HP Treatment Strategies Are Evolving1,2 Conventional treatment by calcium and vitamin D does not fully replace the functions of PTH and can lead to: Short-term complications of hypocalcemia, hypercalcemia and hypercalciuria Long-term complications of impaired renal function and extraskeletal calcifi
Slide 26: FDA Perspective on Optimal PTH PK Profile
FDA Perspective on Optimal PTH PK Profile1 1 FDA presentation Natpara Advisory Committee September 12, 2014 Natpara QD provides dose-dependent increase in serum calcium for ~24 hours Natpara QD effect on urinary calcium excretion is short-lived (10-12 hours) as kidney reabsorption of calcium follows
Slide 27: Continuous PTH Infusion Led to Improved Outcomes
Continuous PTH Infusion Led to Improved Outcomes Desired Treatment Outcomes in HP Natpara Once-daily1, 2 PTH (1-34) Infusion3-9 Increase serum calcium Reduce pill burden Normalize urinary calcium excretion X Reduce hypercalcemia X Reduce hypocalcemia X Normalize serum phosphate (high-normal range) N
Slide 28: TransCon PTH Design
TransCon PTH Design Predictable release of parent drug in the body PTH(1-34) PTH(1-34) TransCon carrier TransCon linker Inactive Prodrug Creation of TransCon prodrug TransCon PTH is a sustained-release prodrug, designed to provide stable free PTH levels in the physiological range for 24 hours a day
Slide 29: TransCon PTH Phase 1 Trial Design
TransCon PTH Phase 1 Trial Design Randomized, placebo controlled, single and multiple ascending dose trial to evaluate the safety, tolerability, PD and PK of TransCon PTH in healthy adults Primary Objective: To assess the safety and tolerability of single and 10 multiple daily doses of TransCon PTH
Slide 30: Expectations for Phase 1 Trial in Healthy Volunteers
Expectations for Phase 1 Trial in Healthy Volunteers1 1 Journal of Bone and Mineral Research, Vol. 26, No. 9, September 2011, pp 2287–2297 7-Day Continuous Infusion of PTH(1-34) in Healthy Adults1 Dose-dependent increase in serum Ca Small increase in urinary Ca excretion despite elevated serum Ca Do
Slide 31: Supports Infusion-Like Profile with Daily Administration
Supports Infusion-Like Profile with Daily Administration TransCon PTH phase 1 data reproduced PK profile from preclinical studies and showed t1/2 of ~60 hours (versus Natpara t1/2 ~3 hours) TransCon PTH 100 µg (n=8)
Slide 32: Single Dose Provided Sustained Calcemic Effect
Single Dose Provided Sustained Calcemic Effect TransCon PTH led to sustained elevation of serum calcium lasting more than 72 hours with low inter-subject variability TransCon PTH 100 µg (n=8)
Slide 33: Expected Effect of TransCon PTH on Renal Calcium Excretion Observed in Phase 1
Expected Effect of TransCon PTH on Renal Calcium Excretion Observed in Phase 1 1 J Bone Miner Res, 2011, 26(9), 2287–2297 2 JCEM, 2001, 86(4), 1525-1531 Despite increased serum Ca at 11 mg/dL fractional calcium excretion remained normal and far below the 6.5% range reported for healthy volunteers cl
Slide 34: Dose-Dependent Increase of Serum Calcium
Dose-Dependent Increase of Serum Calcium Dose response and low inter-subject variability suggests ability to titrate and individualize dosing TransCon PTH 48, 72 and 100 µg (n=8/group)
Slide 35: Dose-Dependent Endogenous PTH(1-84) Response
Dose-Dependent Endogenous PTH(1-84) Response TransCon PTH provided dose-dependent down regulation of endogenous PTH(1-84) TransCon PTH 48, 72 and 100 µg (n=8/group)
Slide 36: TransCon PTH: Highlights
TransCon PTH based on parent drug PTH(1-34) with clinical proof-of-principle in HP and validated TransCon technology Interim phase 1 data supports target product profile as a true replacement therapy for HP Phase 1 full data set expected Q2 2018 Planning pathway to phase 3: Extensive clinical experi
Slide 37: TransCon CNP: Once-Weekly CNP for Achondroplasia
TransCon CNP: Once-Weekly CNP for Achondroplasia
Slide 38: Achondroplasia – Not Only a Skeletal Disease
Achondroplasia – Not Only a Skeletal Disease Autosomal dominant genetic disorder Patients suffer numerous comorbidities No FDA-approved therapy Only option to improve height is surgical limb lengthening Most common form of human dwarfism Approximately 250,000 patients worldwide1 80% born to average-
Slide 39: Normal Growth Depends on Balanced Pathways
Normal Growth Depends on Balanced Pathways TransCon CNP is designed to provide continuous exposure to a CNP analogue to optimize efficacy with a well-tolerated and convenient once-weekly dose CNP Activity FGFR3 Activity Normal growth Achondroplasia growth CNP FGFR3 FGFR3 CNP
Slide 40: Clinical Proof of Principle in Achondroplasia
Clinical Proof of Principle in Achondroplasia 1 Biomarin R&D Day, April 2016 Therapeutic Goal: Optimize CNP efficacy with a well-tolerated and convenient dosage form Vosoritide (CNP analog) in phase 3 for achondroplasia; reported promising height velocity data Effects on growth at 12 months with 46-
Slide 41: TransCon Technology Offers Potential Solution
TransCon Technology Offers Potential Solution Predictable release of parent drug in the body CNP TransCon carrier TransCon linker Inactive Prodrug Creation of TransCon prodrug CNP TransCon technology provides effective shielding of CNP: From neutral endopeptidase degradation in subcutaneous tissue a
Slide 42: TransCon CNP Weekly Profile Confirmed in Primates
TransCon CNP Weekly Profile Confirmed in Primates TransCon CNP following SC injections in cynomolgus monkeys (n=3)1 No cardiovascular adverse effects observed in preclinical models at doses exceeding the expected clinical dose 0 24 48 72 96 120 144 168 0 500 1000 1500 2000 2500 Hours Total CNP (ng/m
Slide 43: Continuous Infusion More Effective Than Daily
Right tibia length (mm, ±SEM) Mouse growth study right tibia length 50 nmol/kg/day (n=9/group)1 Same amount of CNP given as continuous infusion in mice is more efficacious than daily SC injection over 35 days Same effect demonstrated for Ascendis CNP peptide Vosoritide* Infusion Vehicle Vosoritide*
Slide 44: Well Tolerated Safety Profile
Well Tolerated Safety Profile No adverse hemodynamic effects (e.g., hypotension) in cynomolgus monkeys or mice at levels exceeding the expected clinical dose Lack of adverse hemodynamic effect may widen therapeutic window, thereby enhancing efficacy 1 Poster presented at ENDO 2017 * “Vosoritide” ref
Slide 45: Juvenile Cynomolgus Growth Study Completed
Growth velocity of different doses of TransCon CNP Compare weekly TransCon CNP to daily vosoritide Juvenile Cynomolgus Monkeys Bone length assessed over 6 months Other endpoints/ markers of CNP bioactivity: bone turnover markers, urinary cGMP TransCon CNP Weekly Dosing Vehicle Vosoritide* Daily Dosi
Slide 46: Juvenile Healthy Monkey Growth Study
Percentage change from baseline (Mean +SD) Juvenile Healthy Monkey Growth Study Demonstrated dose-proportional tibial linear growth; ulnar growth consistent Compared to untreated control, growth increased >70% with highest TransCon CNP dose vs. 35% with vosoritide* at a higher weekly dose 1 Poster p
Slide 47: TransCon CNP in Achondroplasia Disease Model
TransCon CNP/ Vehicle Vehicle TransCon CNP may ameliorate most disabling achondroplasia traits, including stenosis of the foramen magnum TransCon CNP in Achondroplasia Disease Model (Fgfr3Y367C/+)1 Preventing Premature Fusion of Synchondroses of Foramen Magnum Linear and Skeletal Growth in Achondrop
Slide 48: TransCon CNP: Highlights
TransCon CNP: Highlights TransCon CNP leverages Ascendis technology platform to develop a once-weekly administration, without dose-limiting cardiovascular adverse effects Shields CNP from NPR-C receptor clearance and NPR-B induced-hypotension Prolonged half-life extension and efficacy trend observed
Slide 49: Selected Expected Milestones
fliGHt (switch) Trial enrollment completion Selected Expected Milestones heiGHt Trial top-line Ph3 results TransCon PTH: Ph3 initiation Q1 2019 TransCon PTH: Ph1 SAD results TransCon CNP: - Ph1 results - Initiate ACH natural history study TransCon PTH: Full Ph1 results TransCon CNP: Ph1 dosing Q4 20
Slide 50: Three Product Opportunities: >$1 Billion Each
Three Product Opportunities: >$1 Billion Each Efficacy without potential dose-limiting cardiovascular adverse effects; once-weekly dosing in achondroplasia Phase 1 to be initiated 2018; data Q4 2018 TransCon Growth Hormone TransCon PTH TransCon CNP Infusion-like profile potentially addresses all asp
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