ABCL635 Reduced Vasomotor Symptom Frequency and Severity in Phase 2 Trial

A single subcutaneous dose of ABCL635 significantly reduced the frequency and severity of moderate-to-severe vasomotor symptoms due to menopause over 4 weeks, according to topline phase 2 results announced by AbCellera.

ABCL635 is an investigational neurokinin 3 receptor antagonist antibody being developed as a nonhormonal, long-acting treatment for moderate-to-severe vasomotor symptoms, commonly known as hot flashes. The multicenter, randomized, double-blind, placebo-controlled phase 2 portion of the study enrolled 92 postmenopausal women experiencing a mean of approximately 10 moderate or severe hot flashes per day. Participants were randomly assigned 1:1 to receive a single subcutaneous 600-mg dose of ABCL635 or placebo.

At week 4, ABCL635 reduced the daily frequency of moderate-to-severe vasomotor symptoms by a mean 8.8 events from baseline compared with a mean reduction of 3.5 events with placebo, for a placebo-adjusted treatment difference of 5.3 events per day (P<.001). Mean percent reduction in symptom frequency was 83% with ABCL635 vs 33% with placebo.

How did ABCL635 affect vasomotor symptom severity?

ABCL635 also significantly improved vasomotor symptom severity. At week 4, mean severity score decreased by 1.4 points with ABCL635 compared with 0.3 points with placebo, for a placebo-adjusted treatment difference of 1.1 points (P<.001).

Mean percent reduction in vasomotor symptom severity from baseline to week 4 was 58% in the ABCL635 group compared with 12% in the placebo group. According to AbCellera, statistical significance for both frequency and severity was maintained from week 1 through week 4.

Meaningful improvements also were observed in patient sleep scores and Patient Global Impression of Change, the company reported.

“The four-week data for the Phase 2 study of ABCL635 demonstrate a new efficacy benchmark for the reduction of hot flashes both in frequency and severity, as well as improvements in sleep,” JoAnn V. Pinkerton, MD, women’s midlife professor of obstetrics and gynecology at the University of Virginia School of Medicine, said in the announcement. “If validated in Phase 3, ABCL635 could offer a new treatment option with a more convenient dosing regimen and potentially less toxicity.”

What safety findings were reported?

ABCL635 was well tolerated over the 4-week treatment period, according to the company. No serious adverse events, severe adverse events, or adverse events leading to study discontinuation were reported.

The most common adverse events occurring more often with ABCL635 than placebo were headache, fatigue, and injection site reaction.

“These data indicate that ABCL635 could offer menopausal women a well-tolerated, long-acting treatment that has the potential to markedly improve their quality of life,” Sarah Noonberg, MD, PhD, chief medical officer of AbCellera, said in the announcement.

Why is this relevant to primary care?

Vasomotor symptoms are among the most common and disruptive symptoms of menopause and can affect sleep, concentration, energy, mood, work, social activities, and relationships. AbCellera estimated that approximately 12 million women in the US experience moderate-to-severe vasomotor symptoms, with more than 6 million seeking treatment.

For primary care clinicians, the findings are relevant because many patients seek menopause symptom management in primary care, and treatment decisions often require balancing symptom burden, patient preference, contraindications or hesitancy around hormone therapy, and access to nonhormonal options.

The phase 2 data suggest ABCL635 may offer a long-acting, nonhormonal approach if later-stage trials confirm efficacy and safety. However, the results are topline, limited to 4 weeks of follow-up, and ABCL635 remains investigational. The company stated that the antibody targets NK3R, a clinically validated G protein-coupled receptor expressed on KNDy neurons in the hypothalamus.

Reference

1. AbCellera. AbCellera announces positive top-line phase 2 clinical trial results for ABCL635, demonstrating significant reduction in frequency and severity of vasomotor symptoms and a favorable tolerability profile. Published August 10, 2026.