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Wave Life Sciences (WVE) investor relations material
Wave Life Sciences Stifel Virtual Cardiometabolic Forum summary
Complete event summary combining all related documents: earnings call transcript, report, and slide presentation.
Novel obesity treatment mechanism
GalNAc-conjugated siRNA targets INHBE, a genetically validated liver protein, to induce fat loss while preserving muscle, aiming for healthy, sustainable weight reduction without CNS or GI side effects.
The approach leverages improved oligonucleotide chemistry for enhanced potency and duration, enabling potential once or twice yearly dosing.
INHBE inhibition increases lipolysis in visceral fat, with preclinical models showing weight loss comparable to semaglutide, all from fat, and no muscle loss.
Combination with semaglutide doubles the effect, and INHBE siRNA prevents weight rebound after GLP-1 cessation in animal models.
The mechanism is orthogonal to GLP-1s, acting peripherally and not suppressing appetite or hedonic eating.
Clinical development and trial updates
Phase 1 trial includes healthy overweight volunteers, with subtherapeutic and therapeutic dose cohorts; significant activin reduction and favorable safety observed at both 75mg and 240mg doses.
The 240mg cohort expanded to 32 patients, and a 400mg cohort is underway, with six-month follow-up data expected in Q4 and Q1.
Regulatory progress includes IND acceptance for U.S. expansion, with ongoing safety and target engagement reviews.
Biomarker analysis will include cardiometabolic health indicators, with a focus on fat loss, muscle preservation, and potentially liver fat reduction.
The trial aims to distinguish between fat and total body weight loss, aligning with regulatory emphasis on healthy weight loss and muscle preservation.
Market positioning and future outlook
The therapy is positioned as a monotherapy or maintenance treatment, offering an alternative to GLP-1s with fewer side effects and less frequent dosing.
Manufacturing efficiency and low dosing frequency could enable broader global access and cost advantages over current weekly injectables.
No genetic testing is required for patient selection; the target population is all individuals with obesity, similar to the approach with PCSK9 inhibitors.
The company anticipates Q4 data as a key milestone, with the potential to redefine healthy, sustainable weight loss in the obesity market.
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