ABCL635
Neurokinin 3 Receptor (NK3R)
Vasomotor symptoms (VMS, hot flashes)
Endocrinology / Women’s health
ABCL635 is a potential first-in-class antibody medicine for the non-hormonal treatment of VMS (commonly known as hot flashes) associated with menopause.
ABCL635 specifically targets NK3R, a complex membrane protein found on KNDy neurons in the infundibular nucleus of the hypothalamus that help regulate body temperature. ABCL635 is the first AbCellera-led program generated using our GPCR and ion channel technologies, and we anticipate initiation of clinical trials in Q3 of 2025.
Symptoms experienced during menopause are a significant burden.
VMS are the most frequent reason for seeking medical care for menopause.1 Approximately 30% of women experience moderate to severe VMS,2 and the impact is felt across many aspects of everyday life, including sleep, concentration, energy and mood, work, social activities, and relationships.3
VMS are characterized by a sudden and intense feeling of heat that leads to sweating, chills, and interrupted sleep.3 Typically, VMS episodes can occur 4-5 times per day or more, and may last up to 7 years.4
Menopause hormone therapy (MHT) is the current standard of care for VMS. While it is effective, non-hormonal treatments for VMS are an important option for those who either cannot or choose not to use MHT.5 As an antibody-based therapeutic, ABCL635 has the potential to offer several benefits over existing non-hormonal treatment options, including potential for reduced side-effects and more convenient dosing.
- Williams, RE. et al. Maturitas. 2007;58(4):348-358. doi: 10.1016/j.maturitas.2007.09.006.
- Nappi, RE. et al. Menopause. 2021; 28(8):875-882. doi: 10.1097/GME.0000000000001793.
- Monteleone, P. et al. Nat Rev Endocrinol. 2018;14:199–215. doi: 10.1038/nrendo.2017.180.
- Avis, NE. et al. JAMA Intern Med. 2015; 175(4):531-539. doi: 0.1001/jamainternmed.2014.8063.
- Stute, P. et al. Maturitas. 2022; 164:38-45. doi:10.1016/j.maturitas.2022.06.008.
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.
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 antibody that binds NK3R to prevent activation of KNDy neurons by NKB. Blocking NKB signalling has been shown to rebalance KNDy neuron activity, helping to reduce VMS associated with menopause.
Proposed mechanism of action for ABCL635 based on AbCellera nonclinical data and published literature.