AbCellera reports positive Phase 2 results for ABCL635, showing significant reductions in the frequency and severity of menopausal hot flashes.
Written By: Anamika Koshti, PharmD
Reviewed By: Pharmacally Editorial Team
AbCellera has announced positive top-line results from the Phase 2 portion of its Phase 1/2 clinical trial evaluating ABCL635, an investigational neurokinin 3 receptor (NK3R) antagonist antibody. ABCL635 is being developed as a non-hormonal, long-acting, subcutaneous treatment for moderate-to-severe vasomotor symptoms (VMS), commonly known as hot flashes, due to menopause. The study met its primary efficacy endpoints, demonstrating statistically significant reductions in both the frequency and severity of VMS at week 4 following a single dose compared with placebo.
Phase 2 Trial Design
The randomized, double-blind, placebo-controlled, multicenter Phase 2 portion of the trial (NCT07118891) enrolled 92 postmenopausal women experiencing a mean of approximately 10 moderate or severe hot flashes per day.
Participants were randomized 1:1 to receive either a single subcutaneous 600 mg dose of ABCL635 or placebo.
ABCL635 Reduced Hot Flash Frequency
At week 4, ABCL635 reduced the mean number of moderate-to-severe hot flash events by 8.8 events per day from baseline, compared with a reduction of 3.5 events per day with placebo. This resulted in a mean placebo-adjusted treatment difference of 5.3 events per day (p<0.001).
The mean percentage reduction in VMS frequency was 83% with ABCL635 compared with 33% with placebo, representing a 50% placebo-adjusted treatment difference.
Statistical significance was maintained from week 1 through week 4, with p<0.001 reported across the period.
Reduction in VMS Severity
ABCL635 also produced a significant reduction in VMS severity at week 4. Mean severity scores decreased by 1.4 points from baseline with ABCL635 compared with 0.3 points with placebo, resulting in a mean placebo-adjusted treatment difference of 1.1 points (p<0.001).
The mean percentage reduction in VMS severity was 58% with ABCL635 versus 12% with placebo, corresponding to a 46% placebo-adjusted treatment difference.
Improvements in Sleep and Patient-Reported Outcomes
Meaningful improvements were also observed in patient sleep scores and patient global impression of change (PGI-C). These findings indicate that the reduction in vasomotor symptoms was accompanied by improvements in patient-reported measures during the four-week treatment period.
Favorable Tolerability Profile
ABCL635 was well tolerated throughout the four-week treatment period. No serious adverse events, severe adverse events, or adverse events leading to study discontinuation were reported.
The most common adverse events in the ABCL635 treatment group that occurred more frequently than with placebo were headache, fatigue, and injection-site reactions.
Expert Perspective
JoAnn V. Pinkerton, M.D., Women’s Midlife Professor of Obstetrics and Gynecology at the University of Virginia School of Medicine, said the four-week results demonstrated a new efficacy benchmark for reducing both the frequency and severity of hot flashes while also improving sleep.
She noted that, if the findings are validated in Phase 3, ABCL635 could provide a treatment option with a more convenient dosing regimen and potentially less toxicity.
Sarah Noonberg, M.D., Ph.D., Chief Medical Officer of AbCellera, described the results as a significant milestone for the company and women’s health. She said targeting NK3R with an antibody demonstrated potential best-in-class vasomotor symptom relief over four weeks following a single subcutaneous dose.
ABCL635 Mechanism and Development
ABCL635 specifically targets NK3R, a clinically validated G protein-coupled receptor expressed on KNDy neurons in the infundibular nucleus of the hypothalamus.
The antibody is AbCellera’s first pipeline program from its GPCR and ion channel platform to advance into clinical testing. The program entered the clinic in July 2025.
Vasomotor Symptoms in Menopause
Vasomotor symptoms, including hot flashes and night sweats, are among the most common symptoms associated with menopause and can substantially affect everyday life. The symptoms can interfere with sleep, concentration, energy, mood, work, social activities, and relationships.
According to AbCellera, VMS affects up to 80% of women, and moderate-to-severe VMS affects an estimated 12 million women in the United States, of whom more than six million seek treatment.
VMS can persist for many years after the final menstrual period and are the most frequent reason women seek medical care for menopause.
ABCL635 remains an investigational therapy. The Phase 2 findings provide clinical evidence supporting further evaluation of the antibody as a non-hormonal, long-acting treatment for moderate-to-severe menopausal vasomotor symptoms.
Reference
About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.