Vasomotor symptoms (VMS) are defined as hot flashes and night sweats in menopausal women. As estrogen levels fall during menopause, the neurons believed to be the key modulators of the heat dissipation response become hyperactive. This leads to VMS, including sensations of heat and/or perspiration that generally last several minutes and are often preceded or followed by sensations of cold and/or shivering. Currently approved non-hormonal therapies for VMS do not address the underlying hormonal dysregulation associated with this common symptom of menopause.
MLE-301 directly targets the key neurons that are thought to control heat dissipation. We believe the drug will act to antagonize the human NK3 receptor, a mechanism which is clinically validated to reduce the frequency and severity of VMS in postmenopausal women. Estrogen is known to be a negative regulator of KNDy neurons, which act upstream of heat dissipation effectors. As estrogen levels fall in peri-menopausal women, the absence of estrogen-driven negative feedback causes KNDy neurons to become hypertrophic and hyperactive. This hyperactivity in KNDy neurons is believed to initiate the process that causes VMS.