Our Programs

MLE-301

Highly validated drug target with genetic, pharmacodynamic, and clinical data supporting role in VMS

Millendo Therapeutics is currently advancing the development of MLE-301 for the treatment of vasomotor symptoms (VMS). MLE-301 leverages recent biological insights that elucidated the central regulator of reproductive hormonal signaling, the KNDy (kisspeptin/neurokinin B/dynorphin) neuron. MLE-301 is a potent and reversible antagonist of the human neurokinin 3 receptor, NK3R, and is selective for the NK3 receptor over the NK2 and NK1 receptors. Preclinical studies to enable a first-in-human Phase 1 program with MLE-301 are underway.

MLE-301 impacts the central driver of VMS

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.

MLE-301 diagram

By inhibiting NK3R signaling on KNDy neurons, MLE-301 is intended to reduce KNDy neuron hyperactivity, thereby restoring normal functioning of heat dissipation effectors and resolving the dysregulation that results in VMS. The NK3R is also believed to be a key regulator of heat dissipating neurons, which we believe further supports the potential of MLE-301 to treat VMS. MLE-301 is expected to enter clinical development in 2020.