Wave Life Sciences Ltd. Q2 FY2024 earnings call

• SELECT-HD Clinical Trial: Positive results for WVE-003 in Huntington's disease, showing potent and durable mutant protein lowering with wild-type preservation, and correlation between mutant Huntington lowering and slowing of caudate atrophy. Submitted opt-in package to Takeda, with decision expected by year-end, and engaged regulators on clinical development path for accelerated approval.
• DMD Program: WVE-N531 exon-skipping candidate for DMD, aiming for dystrophin expression >5%. Part A study showed industry-leading exon skipping and high muscle concentrations. Plan to deliver 24-week dystrophin data later in the quarter.
• RNA Editing (WVE-006): AATD candidate, part of collaboration with GSK. RestorAATion-2 trial initiated, expecting proof of mechanism data in Q4 2024. Designed to correct AATD mutation and reduce aggregation.
• GalNAc siRNA (WVE-007): Obesity program targeting INHBE gene, demonstrating potent and durable silencing, preclinical weight loss similar to semaglutide. Plan to file CTA by end of year and initiate clinical trial in Q1 2025.

In the second quarter of 2024, collaboration revenue was $19.7 million compared to $22.1 million in the prior year quarter. Research and development expenses were $40.4 million, up from $33.3 million in the prior year quarter. G&A expenses were $14.3 million, up from $12.3 million in the prior year quarter. Net loss was $32.9 million, up from $21.1 million in the prior year quarter. Cash and cash equivalents ended the quarter at $154 million, with sufficient funds to support operations into the fourth quarter of 2025.

• Expect updates across clinical programs, including DMD dystrophin data in Q3.
• Plan to submit CTA for WVE-007 by end of 2024 and initiate clinical trial in Q1 2025.
• R&D day scheduled for fall to share preclinical data on wholly-owned portfolio.

• Risks associated with clinical trial outcomes not meeting expectations.
• Uncertainties in regulatory approvals and Takeda's opt-in decision.
• Potential differences between actual results and forward-looking statements as discussed in press release and SEC filings.

Q: Regarding conversations with regulators and Takeda's involvement, is Takeda involved in regulatory interactions and feedback on imaging as a biomarker?

A: Takeda is involved in regulatory interactions, and feedback on imaging biomarkers is ongoing with regulators.

Q: On DMD, what's the bar for N531's efficacy?

A: Target is dystrophin expression >5%, with focus on high quantity, quality, and consistency of response.

Q: Clarify Takeda opt-in decision and regulatory feedback timeline, and financing plans.

A: Takeda opt-in decision and regulatory feedback are separate but concurrent events by year-end. Financing plans consider milestones from collaborations and runway extending to Q4 2025.

Q: Details on RestorAATion-2 Q4 readout and biomarker assessment.

A: Proof of mechanism data in Q4 will assess AAT protein concentration and M-AAT versus Z-AAT proportions, evaluating RNA editing in humans.

Q: Insights on caudate atrophy biomarker for HD and study design.

A: Engaged in Huntington Disease Image Harmonization Consortium, using natural history data and imaging to establish caudate atrophy as a predictive endpoint, with potential for 12-18 months to see meaningful changes.

Q: Translatability of RestorAATion-2 dose finding to humans and product profile expectations.

A: Confidence in translatability due to GalNAc conjugation and preclinical modeling, aiming for AAT protein levels surpassing 11 micromolar threshold.

Q: Thoughts on hydrocephalus safety signal in HD and WVE-003's safety profile.

A: WVE-003 study did not observe hydrocephalus, with focus on sparing wild-type Huntington and avoiding nonspecific knockdown-related risks.