AbCellera’s ABCL-635 Cuts Menopause Hot Flashes 83% in Phase II Trial

Key Points

• ABCL-635 reduced moderate-to-severe hot flashes by 83% from baseline after four weeks, compared with 33% for placebo, with a placebo-adjusted reduction of 5.3 events per day. The treatment also improved symptom severity, sleep disturbance and patient-reported outcomes.
• The therapy showed promising short-term tolerability: no serious or severe adverse events occurred in the ABCL-635 group, though headaches, fatigue and one mild, resolved transaminase elevation were reported.
• AbCellera plans to complete 12-week follow-up data to determine dosing frequency, with monthly self-injection considered feasible based on the drug’s 24-day Phase I half-life. The company is prioritizing ABCL-635 and evaluating Phase III options, including a potential head-to-head study.

AbCellera Biologics NASDAQ: ABCL reported top-line four-week results from a Phase II trial of ABCL-635, an investigational non-hormonal treatment for moderate to severe vasomotor symptoms, or hot flashes, associated with menopause.

The randomized, double-blind, placebo-controlled study enrolled 92 post-menopausal patients, exceeding its planned enrollment of 80 patients. Participants were assigned 1:1 to receive a single 600-milligram subcutaneous dose of ABCL-635 or placebo and were followed for 12 weeks for safety, pharmacokinetic and exposure-response assessments.

Reductions in Hot-Flash Frequency and Severity

At four weeks, patients receiving ABCL-635 recorded a mean reduction of 8.8 moderate-to-severe vasomotor events per day, compared with a 3.5-event reduction in the placebo group. The placebo-adjusted treatment difference was 5.3 fewer events per day, according to Chief Medical Officer Sarah Noonberg.

The ABCL-635 group experienced an 83% reduction from baseline in daily moderate-to-severe events, compared with a 33% reduction in the placebo group. The treatment effect was statistically significant by week one, when the company reported a placebo-adjusted difference of 2.6 events per day.

ABCL-635 also improved hot-flash severity. At week four, mean severity scores declined by 1.4 points in the treatment group and by 0.3 points in the placebo group, producing a placebo-adjusted difference of 1.1 points. The company said the mean severity score in the ABCL-635 group declined to a level indicative of mild events, while the placebo group's score remained indicative of moderate events.

• 37% of ABCL-635 patients achieved complete resolution of moderate-to-severe events, versus 2.2% of placebo patients.
• Nearly 61% of treated patients achieved at least a 90% improvement in event frequency, compared with 8.7% of placebo patients.
• 71% of ABCL-635 patients described their symptoms as “much better” on the Patient Global Impression of Change scale, compared with 16% of placebo recipients.

Noonberg said the company observed treatment effects across the subgroup analyses it had evaluated, though additional subgroup data are expected to be presented at medical conferences later this year.

Sleep and Safety Findings

The study also evaluated sleep disturbance using the PROMIS Sleep Disturbance Short Form. Patients treated with ABCL-635 had an approximately nine-point improvement at week four, compared with a 3.5-point improvement among placebo patients, for a placebo-adjusted difference of 5.5 points.

AbCellera characterized the treatment as having a favorable tolerability profile during the first four weeks. Headaches and fatigue occurred more often in the ABCL-635 group, although the company said most headache events were mild and transient and all fatigue events in the active-treatment group were mild. There were no serious or severe adverse events in the ABCL-635 group; the placebo group had one serious adverse event and two severe adverse events.

The company reported one mild event of increased transaminases in the ABCL-635 group. The event occurred during week three and resolved without intervention by week four; the investigator assessed it as unrelated to treatment. AbCellera said it observed no liver safety signals in mean ALT, AST or bilirubin values over the four-week period, and it reported no evidence of gastrointestinal toxicity in the trial.

Development and Commercial Plans

Chief Executive Officer Carl Hansen said AbCellera had defined success entering the study as efficacy comparable with approved small-molecule NK3R antagonists, along with a safety profile that could avoid liver monitoring and a once-monthly self-injection regimen. He said the observed results exceeded the company’s target product profile.

AbCellera compared its results with registrational-study data for fezolinetant and elinzanetant, while acknowledging the limitations of cross-trial comparisons. Noonberg said ABCL-635’s placebo-adjusted reduction of 5.3 events per day compared with reductions of 2.1 to 3.3 events reported in those Phase III studies.

The company plans to complete the study’s 12-week follow-up and use those results to help determine optimal dosing frequency. Noonberg said the data available to date show no apparent waning of activity through four weeks. ABCL-635 had a 24-day half-life in the company’s Phase I study, and AbCellera said it believes monthly dosing is feasible, with the potential for a longer interval to be assessed after the complete 12-week data set is available.

AbCellera also said patients have shown high uptake into an open-label extension study involving repeat dosing. The company expects the 12-week data later this year and described the open-label extension as a subsequent-year data set.

Management said it will discuss late-stage development plans with clinical advisers and regulatory agencies. The company’s initial Phase III concept was similar to programs used for approved small molecules, but Noonberg said the strength of the Phase II results has prompted consideration of a possible head-to-head study. No decisions have been made.

Hansen said AbCellera will prioritize ABCL-635 while continuing development of its broader pipeline, including plans to bring ABCL688 and ABCL386 into clinical development next year.

About AbCellera Biologics (NASDAQ:ABCL)

AbCellera Biologics Inc NASDAQ: ABCL is a biotechnology company specializing in the discovery and development of therapeutic antibodies. The company's technology platform integrates single-cell screening, microfluidics, high-throughput sequencing and artificial intelligence to rapidly identify and optimize antibody candidates against a wide range of disease targets. By combining experimental data with machine learning, AbCellera accelerates early-stage drug discovery and improves the efficiency of lead candidate selection.

AbCellera primarily operates through partnerships with pharmaceutical and biotechnology firms, offering its antibody discovery services on a fee-for-service and milestone-driven basis.

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