Ascendis Pharma A/s · NASDAQ:ASND
Ascendis Pharma A/s — ENDO 2017
25 slides from Ascendis Pharma A/s's conference presentation, Apr 3, 2017
Slide 1: Ascendis Pharma A/S ENDO Data Review
Ascendis Pharma A/S ENDO Data Review April 3, 2017 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 s
Slide 3: Agenda: ENDO 2017 Data Review
Agenda: ENDO 2017 Data Review Introduction – Jan Mikkelsen, Chief Executive Officer Presentation Highlights TransCon Growth Hormone (4 posters) Jonathan Leff, M.D. Chief Medical Officer TransCon PTH (2 posters; one late-breaker) David B. Karpf, M.D. VP, Clinical Development TransCon CNP (2 posters;
Slide 4: TransCon Technology
TransCon Technology Predictable release of parent drug in the body Parent Drug Parent Drug TransCon carrier TransCon linker Inactive Prodrug Predictable release of unmodified parent drugs Parent drugs can be proteins, peptides or small molecules Linker release only dependent on pH and temperature Tr
Slide 5: Product candidate pipeline
Product Candidate Primary Indication Development Stage Potential WW Market1 WW Commercial Rights TransCon Growth Hormone Growth hormone deficiency Phase 3 > $3 billion2 TransCon PTH Hypoparathyroidism Pre-IND > $2 billion3 TransCon CNP Achondroplasia Pre-IND > $1 billion TransCon Ranibizumab Ophthal
Slide 6: TransCon Growth Hormone: Once-Weekly Replacement Therapy
TransCon Growth Hormone: Once-Weekly Replacement Therapy Jonathan Leff, M.D. Chief Medical Officer
Slide 7: 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 Single injection/dose Convenience 31G needle Room temperature storage Device Easy to use Empty-all design (controlled substan
Slide 8: Phase 3 heiGHt Trial design
Phase 3 Study - 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) Screening ≤
Slide 9: Phase 2 Data Provided Foundation for Phase 3
Phase 2 Data Provided Foundation for Phase 3 Same weekly dose 0.14 mg 0.21 mg 0.30 mg 0.21 mg Dose hGH/kg/week: 1 Intergroup differences not statistically significant. 2 Conducted with a previous lower strength version of TransCon Growth Hormone. 26-week treatment period Two thorough PK/PD assessmen
Slide 10: TransCon Growth Hormone Phase 3 Program
TransCon Growth Hormone Phase 3 Program heiGHt Trial (n = ~150) Switch Trial (n= ~150) Extension Trial (n= ~300) TransCon Growth Hormone Phase 3 Program FDA supports size and scope of program for pediatric GHD filing Safety database to be >300 subjects at time of anticipated filing EMA discussions o
Slide 11: Auto-Injector Designed to Optimize Adherence and Compliance
Auto-Injector Designed to Optimize Adherence and Compliance Auto-injector planned 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 temperatur
Slide 12: Extensive Development of Patient-Centric Device
Device development driven by user feedback >70 subjects, caregivers, health care professionals Six human factor usability studies Single use cartridges in 20% dosing increments with a single small injection of <0.60 mL Built to be connected to future IT solutions for improved adherence in real world
Slide 13: TransCon PTH: Once-daily for Hypoparathyroidism
TransCon PTH: Once-daily for Hypoparathyroidism David B. Karpf, M.D. VP, Clinical Development
Slide 14: Hypoparathyroidism - Not Only About Serum Calcium
Hypoparathyroidism - Not Only About Serum Calcium Patients suffer numerous comorbidities: TransCon PTH designed to address limitations of current therapies normalizing blood/urinary calcium levels, serum phosphate and bone turnover Basal ganglia/CNS calcifications Lenticular calcifications/cataracts
Slide 15: Defined PK Profile for PTH Replacement Therapy
Defined PK Profile for PTH Replacement Therapy from FDA1 and NIH2-4 1 FDA presentation Natpara Advisory Committee September 12, 2014 2 JAMA 1996, 276(8): 631-636 3 J Clin Endocrinol Metab 1998, 83(10): 3480-3486 4 J Clin Endocrinol Metab 2013, 88(9): 4214-4220 NIH research in patients with HP shows:
Slide 16: PK Mimics Physiological PTH Levels over Hours
PK Mimics Physiological PTH Levels over 24 Hours Maintained a flat infusion-like profile with once-daily administration Low PTH peak to trough ratio with low variability TransCon PTH Multiple Dose Study in Monkeys (n=6 to 10/group) 1.5 µg/kg 0.5 µg/kg 0.2 µg/kg
Slide 17: Positive PD Profile in Gold Standard Disease Model
Positive PD Profile in Gold Standard Disease Model In contrast to daily PTH(1-84) treatment in TPTx rat model, TransCon PTH: Normalized serum calcium and serum phosphorus Did not cause abnormal increase in bone density Mean w SD Sham Vehicle TransCon PTH (5 µg/kg) PTH(1-84) (70 µg/kg ) Serum Ca (mg/
Slide 18: Reduction in Urinary Calcium Excretion
Reduction in Urinary Calcium Excretion TransCon PTH administration reduced urinary calcium excretion in cynomolgus monkeys Urinary Ca following SC injections in cynomolgus monkeys (TransCon PTH 1µg/kg, n=3) Average Urinary Ca (mmol/L) (+SEM) 24 Hours Post-Dose Pre-Dose
Slide 19: TransCon CNP: Once-Weekly CNP for Achondroplasia
TransCon CNP: Once-Weekly CNP for Achondroplasia Kennett Sprogøe, PhD Senior Vice President, Product Innovation
Slide 20: Achondroplasia – A Serious and Disabling Disease
Achondroplasia – A Serious and Disabling 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 aver
Slide 21: TransCon CNP Designed to Improve Efficacy and Safety
TransCon CNP Designed to Improve Efficacy and Safety TransCon CNP has a very long half-life (~80 hours) providing continuous exposure to CNP with weekly administration No adverse hemodynamic effects (hypotension) in cynomolgus monkeys or mice at levels exceeding the expected clinical dose Lack of ad
Slide 22: Dose Response in Juvenile Healthy Monkeys
Control TransCon CNP 40 µg/kg/week Vosoritide 20 µg/kg/day (140 µg/kg/week) Percentage Change From Baseline Dose Response in Juvenile Healthy Monkeys Healthy monkeys showed dose dependent tibia bone growth compared to vosoritide1; ulna growth data consistent * “Vosoritide” refers to a synthesized mo
Slide 23: TransCon CNP in ACH Disease Model
TransCon CNP/ Vehicle Vehicle TransCon CNP may ameliorate most disabling ACH traits, including stenosis of the foramen magnum TransCon CNP in ACH Disease Model (Fgfr3Y367C/+) Preventing Premature Fusion of Synchondroses of Foramen Magnum Linear and Skeletal Growth in ACH Mice Vehicle TransCon CNP Tr
Slide 24: ENDO Conference Highlights
ENDO Conference Highlights Efficacy without potential dose-limiting cardiovascular adverse effects; once-weekly dosing in ACH IND or equivalent filing expected 4Q 2017 TransCon Growth Hormone TransCon PTH TransCon CNP Infusion-like profile potentially addresses all aspects of hypoparathyroidism Regu
Slide 25: Ascendis Pharma
ascendis LA pharma