Celmatix’s drug program works by mimicking anti-Mullerian hormone, which acts as the molecular break that keeps women from depleting their ovarian reserves too quickly.
Celmatix CEO, Dr. Piraye Beim/Photo Courtesy of Celmatix
The ovary is responsible for so much more than procreation, but to glimpse the current landscape of women’s health care, you would never know it. Piraye Beim, CEO of ovarian health company Celmatix, Inc., is striving to correct this and herald a new era for women by delaying menopause by as much as 15 years.
Beim is working to trigger this revolution through a new understanding of a key part of the human anatomy called the HPG axis and the critical role ovarian function plays outside of reproduction.
“Menopause is seen as natural, so the therapeutic programs are focused on the symptoms of menopause. Hot flashes, for example, or delaying risks associated with menopause like fractures that go along with osteoporosis,” Beim said. “So, if we can reframe it as organ failure, which is what it actually is, then it elevates the therapeutic importance of extending the function of this critical endocrine process.”
Which is why Beim uses the term “ovarian arrest” to describe the end of the biological process whereby a women has used up all of her ovarian reserves, prompting menopause to occur at around the age of 50.
“We want to create the analog to kidney failure or liver failure, or heart failure,” said Beim.
The parallel shouldn’t be difficult to draw, as the onset of menopause has been shown to have a direct link to a woman’s risk of developing a variety of serious chronic conditions.
“We know that 100% of women who survive to middle age will undergo ovarian arrest and menopause, and we see that the age at which a woman goes into menopause significantly correlates with whether she’s going to develop cardiovascular disease, or when she’s going to get Alzheimer’s. Women who have a very early ovarian arrest have a 3X increased risk of developing multiple of those conditions,” Beim said.
Early ovarian arrest can be caused by a number of factors, including chemotherapy-induced ovarian failure (CIOF), which is the basis for Celmatix’s first therapeutic program.
Approximately 2 million women across the U.S., Europe and Japan undergo cancer treatment prior to menopause.
“About half of those women, as a result of being exposed to DNA-damaging agents and chemo, end up experiencing ovarian failure and in some cases, early ovarian arrest, or early menopause, “Beim explained. “So, what happens is that they survive their cancer, but then they go on to develop these other chronic conditions prematurely as a result.”
Celmatix has invested more than half a decade in building the world’s largest multi-omics ovarian health platform, encompassing proprietary data from over half a million unique individuals.
Based on this research, the company has identified and chosen to target anti-Mullerian hormone receptor type 2 (AMHR2).
“Anti-Mullerian hormone was traditionally seen as a male hormone because it’s found in much higher levels in the bodies of boys and men, but in the past decade, people have understood that it actually has a very critical role through agonizing AMHR2 in preserving endocrine function. Effectively, it’s the key regulator of the biological clock,” Beim explained.
Celmatix’s drug program works by mimicking anti-Mullerian hormone, which acts as the molecular break that keeps women from depleting their ovarian reserves too quickly.
“We are developing peptide agonists that have Anti-Mullerian hormone activity and basically recapitulate that natural ligand. Our mechanism is to exogenously add it back into the body and regulate that process through a recombinant peptide and effectively put the brakes back on,” Beim said.
Besides protecting cancer survivors from heart failure and diabetes and providing them with a second chance to become a mom, Celmatix hopes that it can use the same mechanism to treat conditions like endometriosis, Polycystic ovary syndrome (PCOS) and Mosaic Turner syndrome.
While Celmatix is the chief trailblazer in this emerging space, there are other companies, including well-known names like Bayer, jumping on board. In January, 2020, Celmatix announced a partnership with the aspirin king and German development company Evotec to develop pre-clinical programs for common yet underserved conditions such as PCOS.
Afflicting approximately 15% of women worldwide, PCOS occurs when the ovaries produce an abnormal amount of male sex hormones called androgens. Along with infertility, PCOS can lead to irregular menstruation, cysts and weight gain.
“When we’re successful, just given the huge addressable market, I think that we’re suddenly going to see dozens, if not hundreds, of ovarian health companies popping up in the next decade,” Beim said.
The idea of delaying the onset of menopause naturally raises questions about the pros and cons of pregnancy at an advanced age, but Beim made it clear that this is not Celmatix’s mission and made an important distinction.
“Fertility declines about a decade before the endocrine function of the ovary declines. When you go into menopause at 50, that doesn’t mean that you’re fertile until 50. If you go into menopause at 50, that means that you’re fertile until about 40,” she said. “When we say that we want to push the function of the ovary out, we don’t mean necessarily that we can extend fertility until 60 or 70.”
While Celmatix’s lead program in the high-need CIOF space is currently garnering the most attention, Beim stated that menopause control is the real “moonshot.”
“Potentially, this could be something that, like the birth control pill, could probably be used to help women control their menopause transition,” she said.
Celmatix is currently in the process of finalizing its preclinical work in CIOF with the intention of entering IND-enabling studies in late 2021 or early 2022 and heading into the clinic in 2023.
With an extensive platform and just about half the world’s population to serve, Beim teased that there is more on the immediate horizon.
“Like a true platform, we have other announcements to make later this year,” Beim said.
