W ave Life Sciences: Exon Skipping Approach for the Potential - - PowerPoint PPT Presentation

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W ave Life Sciences:

Exon Skipping Approach for the Potential Treatment of DMD

Little Steps Association DBMD Patient Conference June 6, 2018

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Disclosures

• Dr. Dor is not an employee of Wave Life Sciences,

consultant or otherwise affiliated with Wave Life Sciences

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• Wave is developing rationally-designed stereopure nucleic acid therapeutics
• Utilizing multiple modalities including antisense, exon skipping and RNAi
• Expertise and core focus in central nervous system and neuromuscular conditions
• Global company with manufacturing capabilities

Who is Wave Life Sciences?

Biotechnology company focused on delivering targeted therapies for patients with serious, genetically defined diseases

Source: Wave Life Sciences

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Wave Life Sciences current DMD pipeline

DI SEASE NEXT ANTI CI PATED MI LESTONES TARGET BI OMARKER

Duchenne muscular dystrophy 51 exon 51 dystrophin Trial initiated November 2017 exon skipping exon skipping Phase 1 Duchenne muscular dystrophy 53 exon 53 dystrophin Trial initiation Q1 2019

Research projects exploring additional exon targets currently ongoing

MECHANI SM Source: Wave Life Sciences

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WVE-210201: in vitro exon 51 skipping efficiency

0.3 1 3 10 30 20 40 60 80 100

Treatment Concentration ( M) PS ASO WVE-210201 PMO ASO

PMO ASO = Morpholino Antisense Oligonucleotide; PS ASO = Phosphorothioate Antisense Oligonucleotide; RNA skipping determined by quantitative RT-PCR.

Dose Response on Skipping Efficiency (mRNA, in vitro) (4 Days)

WVE-210201 demonstrated a dose-dependent increase in skipping efficiency in vitro

Source: Wave Life Sciences

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• WVE-210201 Phase 1 clinical trial (ClinicalTrials.gov Identifier: NCT03508947)

– Design: Multicenter, double-blind, placebo-controlled, single ascending dose study with intravenous administration – Primary endpoint: Safety and tolerability – Inclusion criteria: ages 5 to 18, amenable to exon 51 skipping

• Ambulatory and non-ambulatory boys eligible, including those previously treated with eteplirsen (following

appropriate washout period)

• No muscle biopsy required for entry into phase 1 study

– Study sites: North America and Europe – Randomization: 3: 1, active treatment to placebo; 40 boys total – Enrolling; readout expected in the third quarter of 2018

Exon 51: WVE-210201 clinical program

Current Study – Phase 1 trial to evaluate safety and tolerability

Source: Wave Life Sciences; ClinicalTrials.gov (I dentifier: NCT03508947)

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• WVE-210201 planned open-label extension (OLE) of Phase 1 safety study

– Includes muscle biopsy and ≥ 2-years of follow-up

• WVE-210201 planned efficacy study being designed with the DMD community at large and

with feedback from regulatory authorities. Preliminary considerations: – Design: Double-blind, placebo-controlled, multi-dose study assessing dystrophin expression and clinical outcomes – Interim analysis of dystrophin expression in muscle biopsies – Data readout anticipated in the second half of 2019

Exon 51: WVE-210201 clinical program

Next Steps – Planned Open Label Extension and Planned Efficacy Study

Source: Wave Life Sciences