The average life expectancy for women doubled in the last century and now extends well into their 80s. Yet an epicenter of their health — their ovaries — ceases to function decades sooner, contributing to broader health challenges.
Enter Celmatix Therapeutics, Inc., a New York-based preclinical women's health therapeutics company founded in 2009. The company is developing a novel product to extend ovarian function and improve women’s long-term health.
Celmatix is focused on expanding the lifespan of the ovarian reserve — all of the eggs a woman is born with. Improvement of ovarian health may have benefits that extend to other organ systems, including the cardiovascular, musculoskeletal and neurological systems, potentially reducing the risk of disorders such as heart disease, autoimmune diseases, osteoporosis and neurocognitive decline later in life.
"Even though women statistically outlive men by a few years, we spend 25 percent more of our lives living with illness. We are disproportionately impacted by chronic diseases and diseases of aging," explained Piraye Yurttas Beim, PhD, founder and CEO of Celmatix. "We are developing drugs that would help women not just survive into their later years, but really thrive."
Celmatix Takes Aim at Root Causes of Women’s Health Conditions
Using what Beim calls a "female first" approach, Celmatix is designing disease-modifying drug candidates that take aim at the root causes of women’s health conditions, rather than addressing only symptoms. During the first 10 years of its existence, Celmatix accumulated and analyzed data sets to scrutinize female biology on a cellular and molecular level.
The Celmatix team discovered key traits that informed the direction of their product design. First, they learned that the ovary is much more than a reproductive organ. Its functions a hub for the complex endocrine signaling system, which enables broad impacts on a woman's overall health. Moreover, the root causes of gynecologic disorders such as endometriosis and polycystic ovary syndrome (PCOS) result from the disruptive molecules that can also trigger other conditions.
In addition, the Celmatix team gleaned insights into the role of inflammation in women's health. Inflammation has long been implicated in other diseases, including cancer, heart disease, Alzheimer's disease and autoimmune disorders.
"In many ways, these clinically distinct conditions are all the same underlying disease with the same fundamental biology," Beim asserted. "So, when we see endometriosis in a young woman, it's like the canary in the coal mine. It's an early indicator that she may have inflammation that, left untreated, could raise the risk of these other diseases later in life.
"We need to flip the model," she continued. "Even if we put a fraction of our resources into inflammatory conditions that we find early in life, like endometriosis, we may actually be preventing those later-in-life diseases as well. It's a way to not only give a woman better quality of life early in her life, but help her to age in a healthier way to reduce her risk of these chronic diseases down the road."
Countering Ovarian Aging with Novel Therapeutics
Celmatix is developing an innovative drug that activates the anti-Müllerian hormone (AMH) receptor. AMH affects how quickly the ovarian reserve, which is finite at birth, declines as a woman ages. The biological clock puts the brakes on the AMH receptor.
"AMH is a molecular brake that prevents ovarian reserve from depleting too early in a woman’s life. Some women naturally have a stronger set of brakes and some have lighter brakes," Beim explained. "We're working to slow the speed of ovarian decline with an AMH agonist that will allow us to modulate the 'brakes' on ovarian function depletion."
Once the drug gets to the clinical trials stage, Celmatix plans to evaluate it first in women whose ovarian function is at risk of being adversely affected by cytotoxic chemotherapy for premenopausal cancer. Animal studies have already shown that agonizing the AMH receptor during exposure to chemotherapy protects ovarian function.
"In the United States, about 600,000 women receive chemotherapy for cancer before menopause. Those who survive their cancers have to deal with the consequences of losing ovarian function early in life, including severe menopausal symptoms," said Beim. "This has a big impact not only on their long-term health, but also their quality of life."
The AMH agonist under development is part of the Celmatix pipeline, which also includes two product candidates to target infertility and a JNK inhibitor for endometriosis. The latter drug, if approved, would be the first disease-modifying immunotherapy for endometriosis, with potential applicability to PCOS and ovarian aging as well.
Taking a Passion for Women's Health to a Commercial Level
Through academic research during her PhD and as a postdoc, Beim has maintained a commitment to women's health. Taking that passion to the level of a commercial company has generated rewards she does not feel she could have gotten in an academic setting.
"I really wanted to have a platform to more efficiently translate the discoveries I was making as a scientist to improving clinical outcomes,” said Beim. “If you can do groundbreaking science within the context of a startup like Celmatix Therapeutics, you can get much closer to having an impact on patients, and that was very important to me."
She also feels that she has been able to access more resources through investment capital, revenue and philanthropic grants than if she had remained an academic investigator.
Her experience in academia, however, set her up for success in the commercial world.
"The biosciences PhD lifecycle very closely resembles the lifecycle of a startup," she explained. "You have to identify an area of unmet medical need, come up with a creative solution, mobilize resources, communicate your findings, publish and graduate, and that's the same lifecycle for innovation and entrepreneurship as well."
She contends that pursuing a PhD taught her how to learn.
"Learning the business specifics is easier now. There are more resources than when I started in 2009 — like incubators, accelerators and training programs," she concluded. "I learned a lot about entrepreneurship from helping get a lab off the ground and getting a PhD or postdoctoral project going. It would be great for the field if more academic scientists felt empowered to get their innovations into the private sector."