Wave Life Sciences Ltd. Q3 FY2024 earnings call

Management Statement and Operational Highlights

• Year Progress: 2024 saw execution ahead of plan, delivering three positive clinical data sets, FDA support for HD, advancement of obesity program, and balance sheet strengthening.
• AATD: First clinical demonstration of RNA editing in humans with WVE-006; multi-dose data expected in 2025.
• Obesity: WVE-007 has potential to address unmet weight loss needs with preclinical data showing muscle mass retention and synergy with GLP-1s.
• DMD: FORWARD-53 trial interim results showed promising dystrophin expression and safe profile, with 48-week data expected Q1 2025.
• HD: WVE-003 showed correlation between mutant Huntington reduction and caudate atrophy; FDA open to using caudate atrophy as an endpoint for accelerated approval.

Segment Performance

• AATD: In October, delivered proof of mechanism data from the RestorAATion-2 study of WVE-006 in AATD patients, with 6.9 micromolar of M-AAT observed 2 weeks post single dose and durable effect. Multi-dose data from RestorAATion-2 is expected in 2025.
• Obesity: Advancing WVE-007, a GalNAc-siRNA targeted inhibit E for weight loss. On track to file a CTA by the end of 2024 and initiate a clinical trial in the first quarter of 2025. Preclinical data shows potential to address unmet needs in weight loss, including muscle mass retention and synergistic effect with GLP-1s.
• DMD: Interim results from the FORWARD-53 trial of WVE-N531 showed a mean muscle content adjusted dystrophin of 9% after 24 weeks, safe and well tolerated. 48-week dystrophin data is expected in Q1 2025.
• HD: WVE-003 showed potent mutant Huntington silencing and preservation of wild-type HTT. Initial FDA feedback was supportive, and focus is on finalizing the design of a global potentially registrational phase 2/3 study, including submission of an IND application in the second half of 2025.

Guidance

• 2025 Milestones: Aim to build on momentum with key milestones including advancing WVE-N531 and WVE-003 towards potential accelerated approval, multi-dose data for WVE-006, and initiation of WVE-007 clinical trial Q1 2025.
• Submissions: Intent to file CTA for WVE-007 by end of 2024 and submit IND for HD program in second half of 2025.

Risks

• Clinical Trial Uncertainties: Potential failure of trials or inability to meet endpoints.
• Regulatory Hurdles: FDA may not approve accelerated pathways or require additional data.
• Competition: Competition from other companies developing similar therapies.

Question and Answer

• Q: On AAT program, key efficacy assessments and assessing protein levels around infections. A: Paul Bolno and Anne-Marie Li-Kwai-Cheung discussed endpoints and no planned challenge protocol.
• Q: Huntington program cost and partnership structures. A: Paul Bolno talked about planning phases, owning the asset, and clinical regulatory path.
• Q: GLP-1 regulatory discussions and weight loss profile. A: Paul Bolno discussed preclinical data and muscle mass retention.
• Q: FDA support for HD and IND submission timing. A: Anne-Marie Li-Kwai-Cheung and Paul Bolno explained FDA support and planning for IND submission.
• Q: DMD other exons and IND timing. A: Paul Bolno mentioned steps for DMD programs and feedback from FDA.
• Q: RNA editing efficiency and partnering. A: Paul Bolno discussed editing efficiency and ongoing partnerships.
• Q: DMD accelerated approval and functional outcomes. A: Paul Bolno talked about dystrophin as a surrogate and clinical outcomes.
• Q: HD partnership and regulatory discussions. A: Paul Bolno discussed regulatory alignment and ongoing partnerships.
• Q: GSK milestones and HD study design. A: Paul Bolno discussed GSK milestones and study design planning.