Earlier this year Celmatix, a New York-based pre-clinical stage biotech company focused on ovarian biology, announced that a second novel PCOS target identified as part of its five-year, multi-target alliance with Evotec, progressed into hit-identification. Building on this success the company is now doubling down on its efforts, and launching a new Polycystic Ovary Syndrome (PCOS) drug program targeting melatonin receptors outside of the central nervous system. The therapeutic drug will address a critical gap in the market for effective first-line treatments for a range of women’s health indications. Although starting with PCOS, there is potential to expand into the treatment of endometriosis and menopausal symptoms.
PCOS is known primarily for being one of the most common causes of female infertility, affecting around 15% of women of reproductive age. However, disrupted ovarian physiology in women experiencing PCOS has also been shown to impact endocrine, immune, metabolic, cardiovascular, and mental health functions. Despite its prevalence, no drug has ever been developed specifically to treat PCOS. The existing standard of care for PCOS focuses on symptom management, including birth control pills to regularize periods, metformin to address insulin resistance, statins to control high cholesterol, ovarian stimulation for ovulatory dysfunction, and cosmetic procedures to remove unwanted hair. The Celmatix program is aimed at restoring ovarian function in a way that addresses the root cause of all these symptoms.
The novel program has emerged from a decade-long multi-omics initiative at the company to understand the molecular and genetic mechanisms underlying ovarian health and conditions like PCOS. Celmatix recently announced findings for which they accepted an award at the 2023 Society for Reproductive Investigation (SRI) meeting in Brisbane, Australia, demonstrating rare functional mutations in the melatonin receptor genes of women with PCOS and the strong association of the melatonin receptor genes with PCOS traits through algorithmic ranking approaches.
Melatonin is a naturally occurring hormone that functions in the central nervous system (CNS), where it regulates the circadian rhythm. Increasing evidence has revealed an additional mechanism for melatonin signaling outside of the CNS, in peripheral tissues (including the ovary). A number of preclinical studies have validated the mechanism of melatonin receptor signaling outside of the CNS and independent studies and clinical trials have demonstrated that melatonin supplements can improve endocrine, metabolic and reproductive traits in women with PCOS and other women’s health conditions, including menopausal symptoms. However, the therapeutic effect from melatonin supplements is small before women develop significant side effects, including drowsiness due to the CNS-activity. Melatonin supplements also have low bioavailability and half-life in the body. Selective melatonin receptor agonists have been developed, however, these compounds were developed as sleep aids and therefore they are potently active in the CNS.
The Celmatix therapeutic program is focused on developing a novel melatonin receptor agonist compound with peripherally-preferred pharmacokinetics to increase therapeutic action at the target tissues, including the ovary, and minimize unwanted side effects like drowsiness.
Dr. Piraye Yurttas Beim, Celmatix Founder and CEO commented: “The ovary is not just an egg factory. It is the central command center of a woman’s body, integrating signals from the body including stress, inflammation, and nutritional status. Light is one of the most powerful signals that enters our body, so it was no surprise to us that genetic differences in how women’s bodies respond to light emerged in our studies as a powerful link to PCOS and PCOS-related traits. We are excited to not just be at the forefront of highlighting the importance of melatonin signaling for ovarian health and function but also pioneering the development of a novel melatonin receptor agonist that acts specifically in the periphery and not the brain. We believe this drug has the potential to support ovarian health throughout a woman’s lifespan, beginning with treating the root causes of PCOS early in life and later through enabling healthier aging for women as their ovarian function declines through the menopause transition.”