Development

AbCellera's NK3R antibody meets both endpoints in Phase II menopause study

AbCellera's NK3R antibody meets both endpoints in Phase II menopause study

AbCellera Biologics (Nasdaq: ABCL) reported that ABCL635, its investigational neurokinin 3 receptor (NK3R) antagonist antibody, met both primary efficacy endpoints in a Phase II proof-of-concept study for moderate-to-severe vasomotor symptoms (VMS) due to menopause — delivering an 83% mean reduction in hot flash frequency after a single subcutaneous dose, compared with 33% for placebo.

The randomized, double-blind, placebo-controlled Phase I/II study enrolled 92 postmenopausal women experiencing a mean of approximately 10 moderate or severe hot flashes per day, randomized 1:1 to a single 600 mg subcutaneous dose of ABCL635 or placebo. At week 4, ABCL635 produced a placebo-adjusted reduction in VMS frequency of 5.3 events per day (p<0.001) and a 1.1-point improvement in severity score (p<0.001), representing placebo-adjusted differences of 50% and 46%, respectively. No serious adverse events, severe adverse events, or discontinuations due to adverse events were reported; the most common events in the treatment group were headache, fatigue, and injection site reaction. Sleep scores and patient global impression of change also improved, though specific figures were not disclosed.

ABCL635 is differentiated from existing therapies by its antibody format. The NK3R target is already clinically validated by Astellas' Veozah (fezolinetant) and Bayer's Lynkuet (elinzanetant), both once-daily oral small molecules, but ABCL635 had an estimated half-life of approximately 24 days in Phase I, potentially enabling monthly subcutaneous dosing. The distinction could be particularly relevant to safety: fezolinetant carries an FDA warning for rare serious liver injury requiring monitoring, while AbCellera has so far reported no liver enzyme elevations with ABCL635. The comparison remains preliminary, however, given the small Phase II dataset and substantially greater exposure accumulated with approved therapies.

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For AbCellera, ABCL635 is the first program from its G protein-coupled receptor (GPCR) and ion channel antibody platform to reach the clinic, entering Phase I in July 2025. Positive Phase II data validate that the platform can generate functional antibodies against a GPCR target — a class historically resistant to antibody drug discovery — and support the company's broader pipeline strategy. The trial enrolled 92 patients against an original design of approximately 80, and the four-week data represent a single time point from a single dose. Whether the effect is sustained, and whether the safety profile holds at scale, will require Phase III evaluation. The company has not disclosed a Phase III timeline.


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