Ascendis Pharma A/s · NASDAQ:ASND
Ascendis Pharma A/s — 39th Annual J.P. Morgan Healthcare Conference (January 2021)
50 slides from Ascendis Pharma A/s's conference presentation, Jan 11, 2021
Slide 1: Ascendis Pharma A/S 39th Annual J.P. Morgan Healthcare Conference
Ascendis Pharma A/S 39th Annual J.P. Morgan Healthcare Conference January 11, 2021 All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation. 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: Company Overview
Company Overview Create best-in-class products addressing unmet medical needs by applying TransCon™ technologies to parent drugs with clinical proof-of-concept or clinically validated pathways Endocrinology rare disease TransCon hGH: Pediatric growth hormone deficiency (GHD): BLA and MAA submitted,
Slide 4: Vision 3x3: Building a Leading BioPharma Company
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 hGH for pediatric growth hormone deficiency TransCon PTH for adult hypoparathyroidism T
Slide 5: Diverse Pipeline of Independent Product Candidates
Diverse Pipeline of Independent Product Candidates 1Excludes rights granted to VISEN Pharmaceuticals in Greater China. 2In phase 3 development for pediatric growth hormone deficiency in Greater China through strategic investment in VISEN Pharmaceuticals. 3US PDUFA June 25, 2021.
Slide 6: Endocrinology Rare Disease
Endocrinology Rare Disease All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.
Slide 7: TransCon hGH: Once-Weekly Replacement Therapy
TransCon hGH: Once-Weekly Replacement Therapy All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.
Slide 8: Growth Hormone Supports Overall Endocrine Health
Growth Hormone Supports Overall Endocrine Health 1de Boer, H. et al. J. Clin. Endocrinol. Metab. 1997; 82(7): 2032-2036. 2Rutherford, O. M. et al. Clin. Endocrinol 1991; 34(6): 469-475. 3Colle, M., J. Auzerie. Horm. Res. 1993; 39(5-6): 192-196. 4Johannsson, G., et al. J. Clin. Endocrinol. Metab. 199
Slide 9: Pediatric GHD Patients Continue Approaching Normal Height
Pediatric GHD Patients Continue Approaching Normal Height Children initially treated with TransCon hGH maintained an advantage in height SDS improvement Height SDS Change from Baseline (LS Mean + SE) TransCon hGH Genotropin Genotropin switch to TransCon hGH heiGHt Trial subjects rolled over into enl
Slide 10: Key Learnings from TransCon hGH Pediatric Clinical Trials
Key Learnings from TransCon hGH Pediatric Clinical Trials TransCon hGH demonstrated a safety profile comparable to that of a daily hGH1 TransCon hGH demonstrated superior AHV2 compared to a daily hGH with a PK profile2 of released hGH that may lead to more efficient utilization by target tissues Dat
Slide 11: Impact of Growth Hormone Distribution
Impact of Growth Hormone Distribution ADIPOSE TISSUE hGH directly stimulates the breakdown of fat1 BONE Optimal growth achieved via direct stimulation of GH receptors in bone and through IGF-11 TransCon hGH is designed to release hGH to achieve the same tissue distribution and receptor activation in
Slide 12: Adult GHD Global Phase 3 foresiGHt Trial Design
Adult GHD Global Phase 3 ForesiGHt Trial Design Primary Objective: Demonstrate efficacy compared to placebo Endpoints Primary: Change from baseline in trunk % fat at 38 weeks Secondary: Change from baseline in trunk fat mass (kg) and total body lean mass (kg) at 38 weeks Exploratory: Total body fat
Slide 13: TransCon hGH: New Paradigm for Growth Hormone Treatment
TransCon hGH: New Paradigm for Growth Hormone Treatment *Conducted by VISEN Pharmaceuticals. In the phase 3 heiGHt Trial, TransCon hGH demonstrated superior AHV (P = 0.009) with a comparable safety and tolerability profile compared to a daily hGH1 In pediatric GHD, submitted BLA June 2020 and MAA Se
Slide 14: TransCon PTH: PTH Replacement Therapy for Hypoparathyroidism
TransCon PTH: PTH Replacement Therapy for Hypoparathyroidism All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.
Slide 15: Hypoparathyroidism
Hypoparathyroidism 1 Nat Rev Dis Primers 2017 Aug 31;3:17055 2Ascendis Pharma HP Patient Experience Research. 3Endo Pract. 2014, 20(7);671-679. 4 J Bone Miner Res 2013, 28: 2570-2576; 5J Clin Endocrinol Metab 2012, 97(12): 4507-4514. 6J Bone Miner Res 2013, 28: 2277-2285. Hypocalcemia Paresthesias,
Slide 16: Chronic Hypoparathyroidism: Significant Patient Population
~86k – 223k 2013, Underbjerg et. al., Cardiovascular and Renal Complications to Postsurgical Hypoparathyroidism: A Danish Nationwide Controlled Historic Follow-up Study 2015, The Epidemiology of Nonsurgical Hypoparathyroidism in Denmark: A Nationwide Case Finding Study 2016, Astor et. al., Epidemiol
Slide 17: TransCon PTH Phase 2 Trial Design
TransCon PTH Phase 2 Trial Design PRO = Patient-reported Outcome. HPES = Hypoparathyroidism Patient Experience Scale. BMD = Bone Mineral Density. TBS =Trabecular Bone Score. DXA = Dual-Energy X-Ray Absorptiometry. FECa = Fractional Excretion of Calcium. 59 adult subjects with HP currently receiving
Slide 18: Preliminary PaTH Forward OLE Safety Summary
Preliminary PaTH Forward OLE Safety Summary TransCon PTH was generally well-tolerated 58 out of 59 randomized subjects currently receiving TransCon PTH in OLE* No drug-related serious TEAEs were reported No TEAEs leading to discontinuation of study drug TEAEs with TransCon PTH reflect known PTH phar
Slide 19: PaTH Forward OLE Mean Active Vitamin D Dose
OLE starts PaTH Forward OLE Mean Active Vitamin D Dose TransCon PTH enabled discontinuation of active vitamin D within two weeks of treatment initiation Preliminary PaTH Forward OLE 6-month data. Data on file. Mean Active Vitamin D Dose µg/day (± SE) Weeks
Slide 20: PaTH Forward OLE Mean Calcium Supplement Dose
OLE starts PaTH Forward OLE Mean Calcium Supplement Dose TransCon PTH enabled rapid and continuous calcium supplement reduction over 6-month study period Preliminary PaTH Forward OLE 6-month data. Data on file. Mean Calcium Dose mg/day (± SE) Weeks
Slide 21: PaTH Forward OLE Mean Serum Calcium and Urine Calcium
Mean Calcium Corrected for Albumin mg/dL (± SE) PaTH Forward OLE Mean Serum Calcium and Mean 24-Hour Urine Calcium Preliminary PaTH Forward OLE 6-month data. Data on file. ULN = Upper limit of normal. Mean 24-hour Urine Calcium mg/24hr ULN (men) ULN (women) Mean 24-hour urine calcium normalized whil
Slide 22: PaTH Forward OLE Change in SF-36 Health Survey Scores
PaTH Forward OLE Change in SF-36® Health Survey Domain Mean Scores (SD) Preliminary PaTH Forward OLE 6-month data. Data on file. Green: Means above lower limit of population norm (47). (SD). *PF (physical functioning), RP (role physical), BP (bodily pain), GH (general health), VT (vitality), SF (soc
Slide 23: PaTH Forward OLE % Change in Mean P1NP and CTx
OLE starts OLE starts PaTH Forward OLE % Change in Mean P1NP and CTx Preliminary PaTH Forward OLE 6-month data. Data on file. At 26-week point, observed lower level of increase for anabolic compared to catabolic bone turnover % Change Procollagen 1N-Terminal Propeptide (± SE) % Change in Mean P1NP %
Slide 24: Bone Mineral Density by DXA
Bone Mineral Density by DXA *A Z-score compares bone density to the average values for a person of the same age and gender. Preliminary PaTH Forward OLE 6-month data. Data on file. With TransCon PTH treatment, BMD mean Z-score trended toward normalization at week 26 At baseline, mean BMD Z-scores* a
Slide 25: PaTHway Phase 3 Trial Design
PaTHway Phase 3 Trial Design 1 Enrollment increased to 76 subjects to ensure evaluable data for 68. 2 If needed to meet recommended dietary intake of calcium, it is permitted to take calcium supplements ≤ 600 mg/day as a nutritional supplement. Double-blind, placebo-controlled trial with an open-lab
Slide 26: TransCon PTH: A Potential PTH Replacement Therapy
TransCon PTH: A Potential PTH Replacement Therapy Phase 1 and phase 2* data support profile of TransCon PTH as a potential PTH replacement therapy for HP Preliminary phase 2 PaTH Forward OLE results at month 6*: 86% of subjects had (1) normal serum calcium, (2) off active vitamin D and (3) taking ≤
Slide 27: TransCon CNP: The New Frontier of Growth Biology
TransCon CNP: The New Frontier of Growth Biology All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.
Slide 28: TransCon CNP - Two Randomized Placebo-Controlled Trials
TransCon CNP - Two Randomized Placebo-Controlled Trials ACcomplisH Trial Sequential rising dose (6, 20, 50, 100 µg/kg) study in cohorts of 12 – 15 subjects, double-blind, randomized 3:1 (TransCon CNP to placebo) Higher dose cohorts initiated following blinded DMC review of prior dose 3-month interim
Slide 29: Oncology
Oncology All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.
Slide 30: TransCon Positioned to Transform Cancer Therapy
TransCon Positioned to Transform Cancer Therapy TransCon systemic and intratumoral technologies designed to enhance anti-tumor effects by Providing sustained modulation of tumor microenvironments Activating cytotoxic immune cells Tumor cells Immune-suppressing cells Cytotoxic T cells and other cance
Slide 31: TransCon Technology: Sustained Localized Release
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
Slide 32: TransCon IT: Potential Paradigm Shift in Intratumoral Delivery
TransCon IT: Potential Paradigm Shift in Intratumoral Delivery TransCon Intratumoral (IT) addresses the problems of conventional IT administration including rapid clearance from the tumor, high systemic exposure and toxicity Data on file. TransCon IT is designed to stay in the tumor and slowly relea
Slide 33: Two Near-term Clinical Candidates – Immunity Cycle
Two Near-term Clinical Candidates – Potential to Address All Steps of the Immunity Cycle Combination approaches enable impact on all critical steps of anti-tumor response TransCon TLR7/8 Agonist for IT delivery and enhanced tumor-antigen presentation TransCon TLR7/8 Agonist TransCon IL-2 b/g TransCo
Slide 34: TransCon TLR7/8 Agonist
TransCon TLR7/8 Agonist TransCon TLR7/8 Agonist All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.
Slide 35: Opportunity for TransCon TLR7/8 Agonist in Solid Tumors
Efficacy Each injection designed to provide sustained exposure in the tumor for months to enhance immune activation Reduce risk of reaching super-high “ablative”, non-immunogenic levels Safety Low systemic toxicity expected to reduce dose-limiting adverse events Infrequent dosing designed to improve
Slide 36: Phase 1/2 Dose Escalation and Expansion Study of TransCon TLR7/8 Agonist
Phase 1/2 Dose Escalation and Dose Expansion Study of TransCon TLR7/8 Agonist Alone or in Combination with CPI MTD = Maximum Tolerated Dose; ORR = Overall Response Rate using RECIST 1.1. Dose Escalation (“3 + 3” Design) Dose Expansion Part 1: Monotherapy Any solid tumor, any line Part 2: Combination
Slide 37: Initial Indication Selection Focus on HPV-associated Cancers
Initial Indication Selection Based on Strong Scientific Rationale to Focus on HPV-associated Cancers HPV-associated: HNSSC, anal, vulvar, penile, vaginal and cervical cancer Melanoma Merkel cell carcinoma Squamous cell carcinoma Gastric cancer Esophageal cancer Hepatocellular carcinoma Non-small cel
Slide 38: TransCon TLR7/8 Agonist: Aiming to Transform How Cancer is Treated
TransCon TLR7/8 Agonist: Aiming to Transform How Cancer is Treated TransCon technology offers a new treatment paradigm for IT sustained delivery with potential for superior efficacy and safety Single IT dose provides exposure for weeks/months Low systemic exposure, well tolerated in mice and non-hum
Slide 39: TransCon IL-2 b/g
TransCon IL-2 b/g TransCon IL-2 b/g All product candidates are investigational. For investor communication only. Not for use in promotion or product commercialisation.
Slide 40: TransCon IL-2 b/g: Optimized b/g Bias, Potency and PK
TransCon IL-2 b/g: Optimized b/g Bias, Potency and PK *Data on file. 1Potency determined in HH cell-based assay expressing IL-2R b/g. 2NHP Study Dose: 0.1 mg/kg. T1/2 ~32 h2 Variant b/g Bias Potency Reduction1 IL-2 No n/a IL-2 b/g 5 kDa Yes ~4-fold IL-2 b/g 10 kDa Yes ~6-fold IL-2 b/g 30 kDa Yes ~20
Slide 41: Increase in Absolute Lymphocyte Count with Minimal Eosinophil Expansion in NHP
Robust Increase in Absolute Lymphocyte Count with Minimal Eosinophil Expansion in NHP Q3W = every 3 weeks. 1Data on file. 2Rosen D, et al. AACR annual meeting. 2020; Poster 4507. 3Rand, et al. J Clin Invest. 1991; 88: 825. 4Van Haelst Pisani C, et al. Blood. 1991;78:1538. Single dose supporting Q3W
Slide 42: CD8+ T Cell and NK Cell Expansion and Activation in NHP
Potent CD8⁺ T Cell and NK Cell Peripheral Expansion and Activation in NHP *Fold change using cell counts derived from hematology lymphocyte counts and flow cytometry-based frequencies within lymphocytes. Data on file. Expansion and activation of cytotoxic lymphocyte subsets observed following a sing
Slide 43: TransCon IL-2 b/g Expands CD8+ T Cell and NK Cell Ratios Over Treg
TransCon IL-2 b/g Expands Ratios of CD8+ T Cells and NK Cells Over Treg Cells in NHP Data on file. Fold change of cell ratios A single dose of TransCon IL-2 b/g resulted in durable and robust increases in the ratios of CD8+ T cells and NK cells over Treg cells in NHP Mean ~5-fold increase of CD8+ T
Slide 44: Evaluation of Immune Memory and Potential Cross-immunity
Syngeneic CT26 tumor model (colon-derived tumor line) Evaluation of Immune Memory and Potential Cross-immunity Following TransCon IL-2 b/g plus TransCon TLR7/8 Agonist Re-challenge of complete responders with CT26 Challenge of complete responders with different tumor type, EMT6 (mammary-derived) Tre
Slide 45: IL-2 b/g plus TLR7/8 Agonist Durable Complete Tumor Regressions
The immune activating mechanism of action of TransCon IL-2 b/g plus TransCon TLR7/8 Agonist and complete responses suggests potential for anti-tumor immune memory TransCon IL-2 b/g Plus TransCon TLR7/8 Agonist Resulted in Durable Complete Tumor Regressions in the CT26 Tumor Model Data on file. Buffe
Slide 46: Potent Immune Memory and Cross-Reactive Anti-Tumor Response
Protection against initial tumor and a new tumor type, suggesting potent anti-tumor memory and cross-reactive anti-tumor immunity Potent Immune Memory and Cross-Reactive Anti-Tumor Response Against a New Tumor Type Data on file. CT26 re-challenge of CRs (colon-derived tumor line) EMT6 challenge of C
Slide 47: Potential Paradigm Shift in How Cancer is Treated
Potential Paradigm Shift in How Cancer is Treated Building a pipeline using TransCon technologies that may enable a new treatment paradigm building upon well-known biology Two product candidates demonstrating potentially best-in-class properties TransCon TLR7/8 Agonist designed for IT, long-term sus
Slide 48: Global Commercial Strategy – Multiple Approaches
Global Commercial Strategy – Multiple Approaches Establishing global commercial presence to deliver potential best-in-class TransCon product candidates to address patients’ unmet medical needs Laying groundwork for successful future endocrinology rare disease launches US commercial organization in p
Slide 49: VISEN Pharmaceuticals
VISEN Pharmaceuticals VISEN was formed in 2018 to develop, manufacture, and commercialize TransCon endocrinology rare disease product candidates in Greater China, the second largest pharmaceutical market VISEN responsible for development, manufacturing and commercialization in Greater China Supports
Slide 50: Selected 2021 Expected Key Milestones
FDA approval of BLA Selected 2021 Expected Key Milestones 50 Q1 2021 Q2 2021 Q3 2021 Q4 2021 Clinical program update Initiate CPI combo dose escalation EC approval of MAA Submit IND or similar Top-line phase 3 results (North America and EU) adult HP File CTN for Japanese adult HP phase 3 Initial res
Ascendis Pharma — 39th Annual J.P. Morgan Healthcare Conference (January 2021) on 6ix