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

W ave Life Sciences: Exon Skipping Approach for the Potential Treatment of DMD Little Steps Association DBMD Patient Conference June 6, 2018 1

Disclosures  Dr. Dor is not an employee of Wave Life Sciences, consultant or otherwise affiliated with Wave Life Sciences 2

Who is Wave Life Sciences? Biotechnology company focused on delivering targeted therapies for patients with serious, genetically defined diseases • 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 Source: Wave Life Sciences 3

Wave Life Sciences current DMD pipeline NEXT ANTI CI PATED MI LESTONES DI SEASE TARGET BI OMARKER MECHANI SM Duchenne muscular dystrophy 51 exon skipping Phase 1 Trial initiated November 2017 exon 51 dystrophin exon skipping Duchenne muscular dystrophy 53 exon 53 dystrophin Trial initiation Q1 2019 Research projects exploring additional exon targets currently ongoing Source: Wave Life Sciences 4

WVE-210201: in vitro exon 51 skipping efficiency WVE-210201 demonstrated a dose-dependent increase in skipping efficiency in vitro Dose Response on Skipping Efficiency (mRNA, in vitro) 100 (4 Days) 80 60 WVE-210201 PMO ASO 40 PS ASO 20 0 0.3 1 3 10 30 Treatment Concentration ( M) PMO ASO = Morpholino Antisense Oligonucleotide; PS ASO = Phosphorothioate Antisense Oligonucleotide; RNA skipping determined by quantitative RT-PCR. 5 Source: Wave Life Sciences

Exon 51: WVE-210201 clinical program Current Study – Phase 1 trial to evaluate safety and tolerability • 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 Source: Wave Life Sciences; ClinicalTrials.gov (I dentifier: NCT03508947) 6

Exon 51: WVE-210201 clinical program Next Steps – Planned Open Label Extension and Planned Efficacy Study • 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 Source: Wave Life Sciences 7