Ascendis Pharma A/s · NASDAQ:ASND
Ascendis Pharma A/s — Investor Presentation (January 2017)
49 slides from Ascendis Pharma A/s's investor presentation, Jan 9, 2017
Slide 1: Ascendis Pharma A/S
Ascendis Pharma A/S Jan Mikkelsen President & CEO January 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
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 wholly-owned pipeline and exp
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: 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
Slide 6: Expected Synergies of Therapeutic Focus
Expertise in endocrinology (clinical, regulatory, medical affairs) Concentrated prescriber audience Small, focused sales force Patient-centric support system Reimbursement and payor knowledge Distribution networks TransCon CNP TransCon Growth Hormone Expected Synergies of Therapeutic Focus TransCon
Slide 7: Building a Leading Company in Rare Diseases
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 8: TransCon Growth Hormone: Once-Weekly Replacement Therapy
TransCon Growth Hormone: Once-Weekly Replacement Therapy
Slide 9: Long-Acting Growth Hormones
Long-Acting Growth Hormones Human Growth Hormone (hGH) is a growing ~$3 billion market Largest indication is Growth Hormone Deficiency (GHD), representing ~50% of the market Pediatric indications comprise up to 90% of the market Current growth hormone therapies require daily injections, which often
Slide 10: GHD – Not Only About Growth
GHD – Not Only About Growth Children with GHD suffer beyond growth failure1 Increased and abnormal fat distribution (especially truncal fat mass) Abnormal metabolic profile Impaired exercise capacity Decreased quality of life Adults with GHD2 Trunk fat accumulation and decrease in lean body mass Dec
Slide 11: Tissue Specific Effects of GH and IGF-1
ADIPOSE TISSUE GH breakdown fat via stimulation of GH receptors in fat, counteracting the lipogenesis effect of IGF-11 Tissue Specific Effects of GH and IGF-1 BONE Optimal growth is achieved via co-stimulation of GH and IGF-1 receptors in bone1 Increasing molecular size through permanent protein mod
Slide 12: Tissue Distribution Associated with Optimal Profile
Tissue Distribution Associated with Optimal Profile 1 J Clin Endocrinol Metab 2007,12: 4529-4535 2 J Clin Endocrinol Metab1997, 82(2): 629-633 3 J Clin Endocrinol Metab 2005 90: 6431–40 4 Pituitary. 2013 Sep;16(3):311-8 Additional published data show that long-acting GH formulations based on unmodif
Slide 13: TransCon GH Designed to Address Issues Raised by Experts
TransCon GH Designed to Address Issues Raised by Academic and Regulatory Experts1 Predictable release of parent drug in the body hGH hGH TransCon carrier TransCon linker Inactive Prodrug Creation of TransCon Prodrug 1 European Journal of Endocrinology (2016) 174, C1–C8 Once-weekly prodrug releasing
Slide 14: Growth Comparable to Daily hGH in Phase 2 Study
Growth Comparable to Daily hGH in Phase 2 Study1 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 Conducted with a previous lower strength version of TransCon Growth Hormone. 26-week treatment period Two thorough P
Slide 15: Dose Proportional IGF-1 Elevation in Phase 2 Study
Dose Proportional IGF-1 Elevation Observed into the Normal Range in Phase 2 Study 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
Slide 16: Comparable hGH Levels in Phase 2 Study
Comparable hGH Levels for TransCon Growth Hormone and Daily hGH in Phase 2 Study Maximum hGH blood concentration comparable between equivalent weekly doses of TransCon Growth Hormone and daily hGH Days (Week 13) hGH serum concentration (+SEM, ng/ml)
Slide 17: Comparable Safety to Daily hGH in Phase 2
Comparable Safety to Daily hGH in Phase 2 >1100 TransCon Growth Hormone injections administered in the Phase 2 pediatric study No reports of lipoatrophy or nodule formation No Serious Adverse Events (SAEs) related to study drug Immunogenic profile comparable to daily hGH Injection site tolerability
Slide 18: Phase 3 heiGHt Trial Ongoing
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 19: Easy to Use Device with Optimal Product Features
Easy to Use Device with Optimal Product Features Auto-injector for commercialization to be used in extension study Simple operation with few user steps A single low-volume injection for all patients (<0.6 mL) Small needle comparable to daily hGH (31G, 4mm) Room temperature storage No waste due to em
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 Single injection/dose Convenience 31G needle Room temperature storage Device Easy to use Empty-all design (controlled substan
Slide 21: TransCon Growth Hormone: Highlights
TransCon Growth Hormone: Highlights Potential best-in-class long-acting growth hormone product profile Phase 3 heiGHt Trial recruiting and initial patients dosed; full enrollment expected 4Q 2017 Commercial scale manufacturing and supply chain established Auto-injector developed and on-track for lau
Slide 22: TransCon PTH: Once-Daily for Hypoparathyroidism
TransCon PTH: Once-Daily for Hypoparathyroidism
Slide 23: Hypoparathyroidism affects 77,000 patients in the U.S.
Hypoparathyroidism affects 77,000 patients in the U.S.1 Patients suffer numerous comorbidities: Hypocalcemia and hypercalcemia Hypercalciuria (stones, nephrocalcinosis) Psychiatric disorders, depression Reduced QOL Until recently, hypoparathyroidism remained among the few hormonal insufficiency stat
Slide 24: FDA Perspective on Optimal PTH PK
FDA Perspective on Optimal PTH PK1 1 FDA presentation Natpara Advisory Committee September 12, 2014
Slide 25: Intermittent PTH Caused Decrease in Cortical BMD
Intermittent PTH Caused Decrease in Cortical BMD Six years of therapy with Natpara was associated with a progressive decrease in cortical BMD1 Continuous exposure to PTH(1-34) restores bone turnover to normal levels while avoiding the overstimulation of daily or twice daily injections2 TransCon PTH
Slide 26: Optimal PTH PK Improved Treatment Outcomes
Optimal PTH PK Improved Treatment Outcomes Physiological Effect in Hypoparathyroidism Natpara Once-daily1, 2 PTH (1-34) Infusion3-6 Increase serum calcium Reduce pill burden Normalize urinary calcium excretion X Reduce clinical hypercalcemia X Reduce clinical hypocalcemia X Normalize serum phosphate
Slide 27: Designed Specifically for Hypoparathyroidism
Designed Specifically for Hypoparathyroidism 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, providing free PTH levels in the physiological range over an ent
Slide 28: PK Profile of TransCon PTH in Cynomolgus Monkeys
Total PTH [ng/mL] PK profile of TransCon PTH in cynomolgus monkeys supports infusion-like profile following daily administration PTH levels following SC injections in cynomolgus monkeys (TransCon PTH 5µg/kg, n=3) Hours 0 4 8 12 16 20 24 28 32 36 40 44 48 0 10 20 30 40 50 60 Desired PK Profile Confir
Slide 29: Designed to Provide Physiological PTH
TransCon PTH is designed to maintain serum PTH levels in the physiological range, mimicking physiological exposure 1 Simulation based on 100 µg QD Natpara and 70 µg QD TransCon PTH; Simulation of 3 repeat doses of Natpara and TransCon PTH at steady state Physiological Range 10-65 pg PTH(1-84)/mL Nat
Slide 30: Dose-Dependent Increase of Serum Calcium
Ca2+ following SC injections in cynomolgus monkeys (TransCon PTH 1µg/kg and 5µg/kg, n=3/group) Dose-Dependent Increase of Serum Calcium Ca2+ [mmol/L] TransCon PTH leads to sustained elevation of serum calcium lasting more than 24 hours with low inter-individual variability Hours 5 µg/kg 1 µg/kg 3.4
Slide 31: Reduction in Urinary Calcium Excretion
Reduction in Urinary Calcium Excretion TransCon PTH administration reduces urinary calcium excretion in cynomolgus monkeys Urinary Ca2+ following SC injections in cynomolgus monkeys (TransCon PTH 1µg/kg, n=3) Avg urinary Ca2+ (mmol/L) (+SEM) 24 Hours Post-Dose Pre-Dose
Slide 32: Thyroparathyroidectomy (TPTx) Model
Thyroparathyroidectomy (TPTx) Model Hypoparathyroidism disease model Rats subjected to thyroparathyroidectomy (TPTx) by removal of the thyroid and parathyroid glands and allowed to stabilize prior to dosing Model characterized by decreased serum calcium and increased serum phosphorus
Slide 33: Normalized Calcium in Hypoparathyroidism Model
Ca2+ following SC injections in a TPTx model (TransCon PTH 5µg/kg, n=9/group) Normalized Calcium in Hypoparathyroidism Model TransCon PTH normalized serum calcium in a relevant disease model of hypoparathyroidism Sham surgery, control TPTx + Vehicle TPTx + TransCon PTH Avg serum Ca2+ (mg/dL) (+SEM)
Slide 34: Reduced Phosphorous in Hypoparathyroidism Model
Serum Phosphorous following SC injections in a TPTx model (TransCon PTH 5µg/kg, n=9/group) Reduced Phosphorous in Hypoparathyroidism Model TransCon PTH normalized serum phosphorous in a relevant disease model of hypoparathyroidism Avg serum P (mg/dL) (+SEM) Sham surgery, control TPTx + Vehicle TPTx
Slide 35: TransCon PTH: Highlights
TransCon PTH: Highlights Development risk lowered as TransCon PTH based on parent drug [PTH(1-34)] with clinical proof of principle and proven TransCon technology Preclinical data mimic [PTH(1-34)] infusion and demonstrate once-daily TransCon PTH address the limitations of current therapies Accelera
Slide 36: TransCon CNP: Once-Weekly CNP for Achondroplasia
TransCon CNP: Once-Weekly CNP for Achondroplasia
Slide 37: 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 38: 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 39: 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 Effective shielding of TransCon CNP From neutral endopeptidase degradation in subcutaneous tissue and blood compartment
Slide 40: TransCon CNP Weekly Profile Confirmed in Primates
TransCon CNP Weekly Profile Confirmed in Primates TransCon CNP following SC injections in cynomolgus monkeys (n=3) Data from ongoing and completed preclinical studies supports weekly dosing in patients with achondroplasia No cardiovascular adverse effects observed in preclinical models
Slide 41: No CV Safety Signals Observed for TransCon CNP
No hypotension or increased heart rate observed in telemetrized cynomolgus monkeys (n=4/group) receiving TransCon CNP BP changes in this study comparable to previous vosoritide study2 No CV Safety Signals Observed for TransCon CNP1 1 “Vosoritide” refers to a synthesized molecule with the same amino
Slide 42: Continuous Infusion More Effective Than Daily
Right tibia length (mm, ±SEM) Mouse Growth Study Right Tibia Length 50 nmol/kg/day (n=9/group) 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 SC
Slide 43: TransCon CNP Improved Phenotype of Achondroplasia Mouse Model
TransCon CNP Improved Phenotype of Fgfr3Y367C/+ Mouse Model of Achondroplasia Fgfr3Y367C/+ + TransCon CNP Fgfr3Y367C/+ + Vehicle In collaboration with
Slide 44: Juvenile Cynomolgus Growth Study Ongoing
Comparing weekly TransCon CNP to a higher cumulative daily dose of vosoritide 6-month data expected in 1Q 2017 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
Slide 45: Juvenile Cynomolgus Growth Study – Interim Data
Change from baseline (mm+SEM) Control TransCon CNP 40µg/kg Weekly Vosoritide 20µg/kg Daily Control TransCon CNP 40µg/kg Weekly Vosoritide 20µg/kg Daily TransCon CNP dose ~1/3 of vosoritide on a weekly basis Both TransCon CNP and vosoritide demonstrated a trend of bone growth over control-treated mon
Slide 46: Juvenile Cynomolgus Growth Study – Dose Effect
Trend towards dose-proportional increase in growth with once-weekly TransCon CNP administration Growth following SC injections in juvenile cynomolgus monkeys at week 8 (n=4) Juvenile Cynomolgus Growth Study – Dose Effect Ulna Tibia Control TransCon CNP 40 µg/kg % Change versus baseline (+SEM) TransC
Slide 47: 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 observe
Slide 48: Selected Expected Milestones & News Drivers
1Q 17 CNP updates 6 months juvenile primate growth study Achondroplasia mouse model PTH filing (IND or equivalent) ENDO presentations (on all programs) PTH Phase 1 study initiation ESPE presentations CNP Phase 1 study initiation Selected Expected Milestones & News Drivers 1Q 17 2Q 17 3Q 17 4Q 17 hei
Slide 49: Building a Leading Rare Disease Company
Building a Leading Rare Disease Company 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 wholly
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