ABCL635
Neurokinin 3 Receptor (NK3R)
Vasomotor Symptoms (VMS) due to Menopause
Endocrinology & Women’s Health
ABCL635 is a potential first-in-class investigational antibody drug candidate for the non-hormonal treatment of moderate and severe VMS (commonly known as hot flashes) due to menopause. ABCL635 selectively targets NK3R, a complex transmembrane protein found on hypothalamic KNDy neurons that helps regulate body temperature. ABCL635 is the first AbCellera-led program generated using its GPCR and ion channel technologies to enter the clinic.
ABCL635 is currently being evaluated in a Phase 1/2 study (NCT07118891). Disclosed top-line results from the Phase 2 portion of the study of ABCL635 at week 4 demonstrated significant reductions in both frequency and severity of moderate and severe VMS, a favorable tolerability profile, and significant improvements in sleep and symptom burden compared to placebo.
ABCL635 is also being developed for the treatment of VMS caused by hormone suppression associated with breast and prostate cancer treatment.
Symptoms experienced during menopause are a significant burden.
VMS are the most frequent reason for seeking medical care for menopause1 and can persist for over four years post the final menstrual period.2 They are characterized by a sudden and intense feeling of heat that leads to sweating, chills, and interrupted sleep.3 VMS have a significant impact on quality of life, are associated with cardiovascular disease risk,4 and result in lost productivity, career advancement, and income.5,6,7
It is estimated that more than 12 million women in the US experience moderate-to-severe VMS, of which more than six million seek treatment.8 Menopause hormone therapy (MHT) is the current standard of care for VMS. While MHT is effective, it is estimated that it is unsuitable for 20% of women due to contraindications or other factors,9 making non-hormonal treatments for VMS an important option for those women.
As an investigational antibody-based therapeutic, ABCL635 has the potential to offer several benefits over existing non-hormonal treatments, and aims to provide a treatment option that has:
- Efficacy comparable to small molecules;
- A differentiated safety profile without the need for liver enzyme monitoring; and
- A convenient once-monthly subcutaneous self-injection.
- Williams, RE. et al. Healthcare seeking and treatment for menopausal symptoms in the United States. Maturitas. 2007;58(4):348-358. doi: 10.1016/j.maturitas.2007.09.006.
- Avis, NE. et al. Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition. JAMA Intern Med. 2015; 175(4):531-539. doi: 0.1001/jamainternmed.2014.8063.
- Nappi, RE. et al. Global cross-sectional survey of women with vasomotor symptoms associated with menopause: prevalence and quality of life burden. Menopause. 2021; 28(8):875-882. doi: 10.1097/GME.0000000000001793.
- Thurston RC, et al. Obstet Gynecol Clin North Am. 2011 Sep;38(3):489-501. doi: 10.1016/j.ogc.2011.05.006.
- Faubion SS, et al. Mayo Clin Proc. 2023 Jun;98(6):833-845. doi: 10.1016/j.mayocp.2023.02.025.
- O'Neill MT, et al. Occup Med (Lond). 2023 Sep 29;73(6):332-338. doi: 10.1093/occmed/kqad078.
- Ko J, et al. Menopause Foundation of Canada; October 16, 2023. Accessed April 24, 2025.
- Management estimate based on US census data, 2023 and References 3, 10, 11.
- Management estimate based on References 3 and 10.
- Stute, P. et al. Evaluation of the impact, treatment patterns, and patient and physician perceptions of vasomotor symptoms associated with menopause in Europe and the United States. Maturitas. 2022; 164:38-45. doi:10.1016/j.maturitas.2022.06.008.
- Todorova, L. et al. Prevalence and impact of vasomotor symptoms due to menopause among women in Brazil, Canada, Mexico, and Nordic Europe: a cross-sectional survey. Menopause. 2023;30(12):1179-1189. doi: 10.1097/GME.0000000000002265.
ABCL635 targets a complex membrane protein on neurons that helps regulate body temperature.
KNDy neurons help maintain body temperature by activating heat dissipation neurons, found in a specialized region of the hypothalamus. Two signals help balance KNDy neuron activity: (1) NKB activates KNDy neurons by binding to a protein on the cell surface called NK3R, (2) Estrogen, produced by the ovaries, inhibits KNDy neurons. In a reproductive state, these two signals are balanced to maintain normal body temperature.
KNDy: kisspeptin, neurokinin B, and dynorphin; NKB: neurokinin B.
During menopause, the ovaries produce less estrogen, resulting in unbalanced KNDy neuron activity. NKB continues to activate KNDy neurons, leading to over-activation of heat dissipation neurons and vasomotor symptoms (VMS).
ABCL635 is an investigational antibody that binds NK3R to prevent activation of KNDy neurons by NKB. Blocking NKB signaling has been shown to rebalance KNDy neuron activity, helping to reduce VMS associated with menopause.
Proposed mechanism of action for ABCL635 based on AbCellera clinical data and published literature.