In This article

• ABCL635 is an investigational, long-acting nonhormonal treatment targeting the neurokinin 3 receptor (NK3R), a pathway involved in the regulation of body temperature.
• In a Phase 2 trial, a single 600-mg subcutaneous dose reduced moderate-to-severe hot flashes by 83% at four weeks, compared with 33% with placebo.
• ABCL635 also reduced the severity of hot flashes, with improvements observed as early as Week 1 and maintained through Week 4.
• Participants receiving ABCL635 reported improvements in sleep and overall assessment of their symptoms.
• The treatment appeared well tolerated over four weeks, but larger and longer studies are needed to determine its long-term safety and durability of benefit.

Vasomotor symptoms (VMS)—commonly referred to as hot flashes and night sweats—are among the most common and bothersome symptoms associated with the menopausal transition. Approximately 80% of women experience perimenopausal VMS, and for some women, symptoms can persist for years. Frequent or severe hot flashes can interfere with sleep, concentration, energy, mood, work, and overall quality of life.

Hormone therapy remains one of the most effective treatments for menopausal vasomotor symptoms. However, some women cannot or do not want to use menopausal hormone therapy, creating an ongoing need for effective non-hormonal treatments. A number of nonhormonal medications are now available or in development, including medications that target the neurokinin system involved in the regulation of body temperature.

A new investigational medication, ABCL635, is generating interest following positive results from a Phase 2 clinical trial. ABCL635 is an antibody that targets the neurokinin 3 receptor (NK3R), the same receptor targeted by the non-hormonal medication fezolinetant (Veozah). Unlike fezolinetant, which is a small-molecule medication taken orally each day, ABCL635 is being developed as a long-acting medication administered by subcutaneous injection.

Targeting the Neurokinin Signaling and Thermoregulation

Within the hypothalamus are specialized neurons known as KNDy neurons, which express neurokinin 3 receptors. These neurons are involved in the brain’s thermoregulatory system. During the menopause transition, declining estrogen levels alter signaling in this system, increasing activity of KNDy neurons and narrowing the body’s thermoneutral zone—the range of temperatures in which the body does not need to activate heat-dissipating mechanisms.

As a result, during the perimenopause, relatively small changes in body temperature may trigger mechanisms such as sweating and increased blood flow to the skin, experienced as a hot flash.

NK3 receptor antagonists work by blocking this signaling pathway. Fezolinetant, an oral NK3 receptor antagonist, was approved by the FDA in 2023 for the treatment of moderate-to-severe vasomotor symptoms associated with menopause.

ABCL635 takes a different approach to targeting the same receptor. Rather than being a small-molecule drug, ABCL635 is a monoclonal antibody designed to bind to and block NK3 receptors. Because antibodies generally remain in the body much longer than small-molecule medications, ABCL635 is being developed as a potentially long-acting treatment.

Phase 2 Clinical Trial of ABCL635

On August 10, 2026, AbCellera announced top-line results from a Phase 2 clinical trial evaluating ABCL635 in postmenopausal women with moderate-to-severe VMS.

In this randomized, double-blind, placebo-controlled study, 92 postmenopausal women, who reported an average of approximately 10 moderate-to-severe hot flashes per day. Participants were randomly assigned to receive either a single 600-mg subcutaneous dose of ABCL635 or placebo.

Key Findings

The primary outcomes of the study were changes in the frequency and severity of moderate-to-severe vasomotor symptoms (VMS). At four weeks, women who received a single dose of ABCL635 experienced:

• Frequency of VMS: An average reduction of 8.8 moderate-to-severe hot flashes per day, compared with a reduction of 3.5 episodes per day with placebo, with an  83% reduction in hot flash with ABCL635 compared with 33% with placebo.
• Severity of VMS: A mean reduction of 1.4 points in hot flash severity with ABCL635 compared with 0.3 points with placebo, with a 58% reduction in VMS severity with ABCL635 compared with 12% with placebo. 
• Early improvement: Reductions in both the frequency and severity of VMS were observed as early as Week 1 and were maintained through the four-week assessment.
• Improved sleep: Participants receiving ABCL635 reported improvements in measures of sleep.
• Favorable short-term tolerability: No serious adverse events or adverse events leading to treatment discontinuation were reported during the four-week treatment period.
• Most common adverse effects: Headache, fatigue, and injection-site reactions occurred more frequently with ABCL635 than with placebo.
• Important limitation: Only 46 women received ABCL635, and follow-up was limited to four weeks. Larger and longer studies will be needed to better characterize the medication’s safety, including the effects of repeated dosing and less common adverse events.

AbCellera has indicated that the Phase 2 findings will inform further clinical development of ABCL635. The company has described the medication as a potential long-acting, nonhormonal treatment for moderate-to-severe menopausal VMS.

The next stage of development will be important for determining how durable the response is, how frequently the medication would need to be administered, and whether the safety profile remains favorable with longer treatment.

The Bottom Line

The treatment landscape for menopausal vasomotor symptoms continues to grow. ABCL635 represents an interesting new approach: rather than altering estrogen levels, it targets the neurokinin 3 receptor involved in the brain’s regulation of body temperature.

In this small Phase 2 study, a single subcutaneous dose of ABCL635 produced substantial reductions in the frequency and severity of moderate-to-severe hot flashes, with improvements also reported in sleep and overall symptom severity. The medication was generally well tolerated during four weeks of follow-up.

These preliminary findings are promising, but they should not yet be interpreted as evidence that ABCL635 is more effective or safer than currently available treatments. Larger and longer clinical trials will be needed to determine how durable the treatment effect is and to establish its longer-term safety.

For women who cannot or prefer not to use menopausal hormone therapy, the development of additional nonhormonal treatments is welcome. ABCL635 is one of several emerging approaches that may expand the options available for managing bothersome menopausal symptoms.

—Ruta Nonacs, MD PhD