Slide 1: Analyst and Investor Call to Review DMD Gene Therapy Presentation at ASGCT
Analyst and Investor Call to Review DMD Gene Therapy Presentation at ASGCT May 15, 2020 1 Property of Pfizer. Not for Distribution.
Slide 2: Disclaimer
Disclaimer This presentation includes forward-looking statements about, among other things, development of Pfizer’s Rare Disease products and product candidates, including our investigational mini-dystrophin gene therapy (PF-06939926), a potential Phase 3 study, our manufacturing capabilities and ca
Slide 3: Introduction
Introduction Mikael Dolsten, M.D., Ph.D. Chief Scientific Officer and President, Worldwide Research, Development, and Medical, Pfizer 3 Property of Pfizer. Not for Distribution.
Slide 4: Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy Hereditary severe X-linked muscular dystrophy • incidence 1:3500-5000 / male live births • absent functional dystrophin protein reduces structural integrity of muscle fibers Delays in motor milestones • diagnosis at ~2-5 years of age • sometimes cognitive impairment
Slide 5: Study Design for Phase 3 Expected to Begin Dosing in 2H 2020
Study Design for Phase 3 Expected to Begin Dosing in 2H 2020 A Phase 3, global, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of PF-06939926 in ambulatory male patients with DMD Eligible patients will be randomized into 2 groups: either Cohor
Slide 6: A Leading Rare Disease Pipeline With 6 New Molecular Entities Expected in Phase 3 by 2H 2020
A Leading Rare Disease Pipeline With 6 New Molecular Entities Expected to be in Phase 3 Studies by 2H 2020 In line Phase 3 Phase 1 & 2 Pre-Clinical Gene Therapy (GTx) 6 Property of Pfizer. Not for Distribution.
Slide 7: Significant Investment in Gene Therapy Manufacturing of Viral Vectors
Significant Investment in Gene Therapy Manufacturing of Viral Vectors to Support Rapid Drug Development and Access Leader in the Manufacture of AAV Vectors using Mammalian Cells: Kit Creek, NC • Three manufacturing facilities (~300,000 sq ft) designed to support DMD and multiple other gene therapy p
Slide 8: Safety and Tolerability of PF-06939926 in Ambulatory Boys with DMD
Safety and Tolerability of PF-06939926 in Ambulatory Boys with Duchenne Muscular Dystrophy Tara McDonnell Moorehead, Florence Yong, Srividya Neelakantan, Katherine Beaverson, David Beidler, Michael Binks Michael Binks, M.D. Vice President, Rare Disease Clinical Research 8 Property of Pfizer. Not for
Slide 9: Developing a Gene Therapy for DMD
Developing a Gene Therapy for DMD PF-06939926 is an AAV9 gene therapy vector containing a miniaturized dystrophin transgene Includes a muscle specific promoter to preferentially express in skeletal and cardiac muscle cells Contains ∆3978 mini-dystrophin transgene Clear dose response on Ratmd
Slide 10: C3391001 (NCT03362502) Design: Ongoing Phase 1b Study
C3391001 (NCT03362502) Design: Ongoing Phase 1b Study Baseline Muscle Month 12 PRIMARY ENDPOINT Biopsy Biopsy Month 2 Muscle Safety through 12 months NSAA Biopsy NSAA Thigh MRI Thigh MRI SECONDARY ENDPOINTS Dystrophin concentration and distribution Long-term safety (5 years) PF-06939926^ Treatment F
Slide 11: C3391001 Study and Safety Status (as of 20th March 2020)
C3391001 Study and Safety Status (as of 20th March 2020*) Phase 1b Study Status 3 Sites in US 9 Participants with DMD Enrolled: • Ambulant and on daily glucocorticoids (GC) • Age mean: 8.8 years (range: 6.2-12.8 years old) • Body weight mean: 27 kg (range: 18-42 kg) • Rise from floor mean: 4 sec
Slide 12: C3391001 Study and Safety Status (as of 20th March 2020)
C3391001 Study and Safety Status (as of 20th March 2020*) Phase 1b Study Status Preliminary Safety Summary 3 Sites in US PF-06939926 intravenous (IV) administration well tolerated 9 Participants with DMD Enrolled: No evidence of hepatic dysfunction or clinically relevant anti-dystrophin resp
Slide 13: Concentration of Dystrophin in Muscle Biopsy by LCMS
Concentration of Dystrophin in Muscle Biopsy by LCMS Novel LC-MS Assay: immunoaffinity liquid chromatography tandem mass spectrometry (IA LC-MS/MS) High sensitivity and reproducibility Wide dynamic range GLP Quality 20 biopsies each from: DMD patients (mean age 6yrs) BMD patients (mean 8yrs) Non-dys
Slide 14: Concentration of Dystrophin in Muscle Biopsy by LCMS
Concentration of Dystrophin in Muscle Biopsy by LCMS Significant and Sustained expression at 12 months Novel LC-MS Assay: immunoaffinity liquid chromatography 1E14 vg/kg 3E14 vg/kg tandem mass spectrometry (IA LC-MS/MS) High sensitivity and reproducibility Mean ±SEM based on data available at each s
Slide 15: Significant and Sustained Distribution of Dystrophin in Muscle Biopsy by Immunofluorescence
Significant and Sustained Distribution of Dystrophin in Muscle Biopsy by Immunofluorescence 1E14 vg/kg 3E14 vg/kg Immunofluorescence Images for 3 High Dose Patients Mean ±SEM based on data available at each scheduled visit * * Red = Dystrophin/ mini-dystrophin expression * * 3E14 vg/kg Dose: Mean %p
Slide 16: NSAA Total Scores Show Improvement Relative to Natural History and Placebo Groups
NSAA Total Scores Show Improvement 12 Months After Treatment Relative to Natural History and Clinical Trial Placebo Groups UK NorthStar Natural History External Placebo (PBO) Control* Bootstrap Distribution of the Mean Change from Baseline to 1-year Post Randomization p = 0.01* Change from Baseline
Slide 17: Whole Thigh MRI – Significant Reduction in Fat Fraction at 2 months
Whole Thigh MRI – Significant Reduction in Fat Fraction at 12 months Relative to Recent Clinical Trial Placebo group (Domagrozumab) Identical Dixon Method Applied to Both Studies Improvement in whole thigh fat MRI Fat Fraction (% Change from Baseline) fraction NS* a. MR scans acquired without compre
Slide 18: Conclusions
Conclusions Preliminary results from the ongoing C3391001 Phase 1b study (NCT03362502) are encouraging For current Cohort 2 (PF-06939926 at 3E14 vg/kg ITR Dose) • PF-06939926 infusion well-tolerated, but complement activation ~5-10 days associated with aHUS-like phenomena o Increased monitoring
Slide 19: Acknowledgments
Acknowledgments We extend our heartfelt ‘thank you’ to all the study participants, their families, researchers, investigators, other clinicians and advocacy organizations for their passion, expertise and engagement, helping to advance clinical research and care for the Duchenne muscular dystrophy co
Slide 20: Q&A Participants
Mikael Dolsten – Chief Scientific Officer and President, Pfizer Worldwide Research, Development, and Medical Q&A Seng Cheng – Chief Scientific Officer and Senior Vice President, Rare Disease Bob Smith – Senior Vice President, Global Gene Therapy, Rare Disease Business Unit Michael Binks – Vice Presi