Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — Muscular Dystrophy Association Clinical and Scientific Conference 2019
25 slides from Wave Life Sciences's conference presentation, Apr 16, 2019
Slide 1: Muscular Dystrophy Association Clinical and Scientific Conference Investor Update
Wave Life Sciences Muscular Dystrophy Association Clinical and Scientific Conference Investor Update April 16, 2019 Exhibit 99.2
Slide 2: Forward-looking statements
Forward-looking statements This document contains forward-looking statements. All statements other than statements of historical facts contained in this document, including statements regarding possible or assumed future results of operations, preclinical and clinical studies, business strategies, r
Slide 3: Paul Bolno, MD, MBA, President and CEO
Paul Bolno, MD, MBA President and CEO
Slide 4: Seeking to transform DMD treatment with stereopure exon skipping approach
Wave Life Sciences: Seeking to transform DMD treatment with stereopure exon skipping approach Exon 51: Wave’s lead development program in DMD High unmet need remains for ~13% of boys with DMD amenable to exon 51 skipping Developing stereopure exon therapies to be more potent than available treatment
Slide 5: Safety and Tolerability of Suvodirsen: Results From a Phase 1 Clinical Trial
Safety and Tolerability of Suvodirsen (WVE-210201) in Patients With Duchenne Muscular Dystrophy: Results From a Phase 1 Clinical Trial Michael Panzara, MD, MPH Chief Medical Officer
Slide 6: Study Objective
Study Objective Primary Objective To evaluate the safety and tolerability of single ascending doses of suvodirsen in patients with Duchenne muscular dystrophy (DMD) Secondary Objective To assess the pharmacokinetic (PK) profile of suvodirsen after single-dose administration
Slide 7: Study Design
Phase 1, multicenter, double-blind, randomized, placebo-controlled trial with 12-week follow-up (NCT03508947) and optional open-label extension Study Design Staggered dosing, beginning with 2 sentinel patients observed for 48 h If neither experienced an SAE, remaining patients in the cohort were tre
Slide 8: Key Enrollment Criteria
Key Enrollment Criteria Ambulatory and nonambulatory male patients 5–18 years old (inclusive) Confirmed DMD gene mutation amenable to exon 51 skipping May have been previously treated with eteplirsen or ataluren, with appropriate washout Prior treatment with drisapersen or gene therapy Key Inclusion
Slide 9: Study Endpoints
Study Endpoints Primary Endpoint Safety and tolerability of suvodirsen, compared with placebo, as assessed by Number (%) of patients with AEs Severity of AEs Number (%) of patients with SAEs Number (%) of patients who withdrew due to AEs Secondary Endpoint Assessment of PK parameters following singl
Slide 10: Patient Disposition
Patient Disposition Screened N=42 Randomized n=36 Suvodirsen1 mg/kg n=6 Suvodirsen2 mg/kg n=6 Suvodirsen 5 mg/kg n=6 Suvodirsen 0.5 mg/kg n=6 Placebo n=10 Open-Label Extension Suvodirsen 7 or 10 mg/kg n=2 n=4
Slide 11: Baseline Demographic and Clinical Characteristics
Baseline Demographic and Clinical Characteristics Characteristic Placebo n=10 Total Suvodirsen n=26 Age, mean (SD), y 8.5 (1.72) 8.0 (2.24) Time since diagnosis, mean (SD), y 4.8 (3.25) 4.6 (2.64) Ambulatory, n (%) 9 (90.0) 22 (84.6) Prior treatment, n (%) 10 (100.0) 26 (100.0) Eteplirsen 1 (10.0) 5
Slide 12: Incidence of Patients With Adverse Events
Incidence of Patients With Adverse Events Suvodirsen was generally safe and well tolerated up to and including 5 mg/kg No serious AEs, discontinuations due to AEs, or deaths in suvodirsen-treated patients Event, n (%) Placebo n=10 Suvodirsen 0.5 mg/kg n=6 Suvodirsen 1 mg/kg n=6 Suvodirsen 2 mg/kg n=
Slide 13: Adverse Events Occurring in ≥2 Patients in an Active Treatment Group
Adverse Events Occurring in ≥2 Patients in an Active Treatment Group AE, n (%) Placebo n=10 Suvodirsen 0.5 mg/kg n=6 Suvodirsen 1 mg/kg n=6 Suvodirsen 2 mg/kg n=6 Suvodirsen 5 mg/kg n=6 Any AE 8 (80.0) 3 (50.0) 5 (83.3) 4 (66.7) 4 (66.7) Any AE occurring in ≥2 patients in an active treatment group P
Slide 14: Infusion-Associated Reactions
Infusion-Associated Reactions IAR, n (%) Placebo n=10 Suvodirsen 0.5 mg/kg n=6 Suvodirsen 1 mg/kg n=6 Suvodirsen 2 mg/kg n=6 Suvodirsen 5 mg/kg n=6 Any IAR 2 (20.0) 0.0 3 (50.0) 1 (16.7) 4 (66.7) IAR occurring in ≥2 patients in any treatment group Pyrexia 0.0 0.0 0.0 0.0 4 (66.7) Headache 0.0 0.0 1
Slide 15: Dose Exploration Above 5 mg/kg Suvodirsen
Dose Exploration Above 5 mg/kg Suvodirsen SMC endorsed exploration of a higher dose as planned per protocol A patient received 10 mg/kg infused over 1 hour Patient experienced pyrexia (39.6°C), headache, tachycardia, and vomiting 4 h after EOI Characterized by investigator as nonserious but severe P
Slide 16: Conclusions
Conclusions Suvodirsen was generally safe and well tolerated at doses up to and including 5 mg/kg Most common AEs were infusion-associated Mild to moderate in intensity Associated with transient increases in hsCRP and complement factor Bb Resolved with symptomatic treatment Increased severity at dos
Slide 17: DYSTANCE 51: A Phase 2/3 Clinical Trial of Suvodirsen in Patients with DMD
DYSTANCE 51: A Phase 2/3 Clinical Trial of Suvodirsen in Patients with Duchenne Muscular Dystrophy
Slide 18: Suvodirsen Induces Potent Exon Skipping in vitro and in vivo Target Engagement
Suvodirsen Induces Potent Exon Skipping in vitro and in vivo Target Engagement in Healthy Nonhuman Primate 5 doses @ 30 mg/kg /week for 4 weeks healthy NHP by subcutaneous dosing Nested PCR Assay Marker 0 µM Skeletal Muscle Tissue (2 fold less lysate) 0.1 µM 0.3 µM 1 µM 3 µM 10 µM Skeletal Muscle Ti
Slide 19: Preclinical and Clinical Data Used to Support Final Dose Selection
Preclinical and Clinical Data Used to Support Final Dose Selection in OLE and DYSTANCE 51 In vitro studies of suvodirsen In vivo study of suvodirsen target engagement in normal monkey Multiple in vitro and in vivo studies in mdx23 mouse Human PK data from Phase 1 study of suvodirsen Both tolerabilit
Slide 20: DYSTANCE Phase 2/3 Trial Study Design
DYSTANCE 51 Phase 2/3 Trial Study Design The DYSTANCE 51 clinical trial has been selected for the US Food and Drug Administration Complex Innovative Trial Design Pilot Program 0 12 24 Week Screening −6 Suvodirsen 3 mg/kg once weekly (~50 patients) Placebo once weekly (~50 patients) Suvodirsen 4.5 mg
Slide 21: DYSTANCE Key Inclusion and Exclusion Criteria
DYSTANCE 51 Key Inclusion and Exclusion Criteria Key Inclusion Criteria Diagnosis of DMD with documented mutation amenable to exon 51 skipping Ambulatory male aged 5–12 years (inclusive) Able to walk independently for ≥10 meters in ≤20 seconds Stable pulmonary and cardiac function Stable systemic co
Slide 22: DYSTANCE Study Endpoints
DYSTANCE 51 Study Endpoints Primary US (and other regions, as applicable): Change from baseline in dystrophin protein levels (western blot of deltoid muscle) through 46 weeks EU (and other regions, as applicable): Change from baseline in NSAA through 48 weeks Secondary Change from baseline through 4
Slide 23: Conclusions
Conclusions Suvodirsen was generally safe and well tolerated at doses up to and including 5 mg/kg Most common AEs were infusion-associated Mild to moderate in intensity Associated with transient changes in hsCRP and complement factor Bb Resolved with symptomatic treatment Increased severity at doses
Slide 24: Suvodirsen: Upcoming milestones
Suvodirsen: Upcoming milestones DYSTANCE 51 (Phase 2/3) Open-Label Extension (OLE) Phase 1 Phase 1 single ascending dose clinical trial Based on in vitro and in vivo preclinical studies and Phase 1 clinical results, two suvodirsen doses selected for Phase 2/3 clinical trial Study complete Multi-dose
Slide 25: Wave Life Sciences Muscular Dystrophy Association Clinical and Scientific Conference
Wave Life Sciences Muscular Dystrophy Association Clinical and Scientific Conference Investor Update April 16, 2019
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