Anti-Mullerian hormone receptor type 2 agonists (Celmatix)

Celmatix Founder and CEO Piraye Yurttas Beim, Ph.D/courtesy of Celmatix The introduction of the birth control pill in 1960 was arguably the last major advancement in a segment of the biopharma industry now known as femtech. That is changing now, as new companies form around de novo innovations that promise important advances for women’s healthcare. Many of these advances are still in preclinical development, but Global Market Insights predicts the worldwide market for therapeutics designed specifically for conditions and diseases that affect only (or mainly) women will exceed $65 billion by 2027. Here are three femtech companies to keep an eye on. Celmatix: Ovarian Health The complexities of the female body extend beyond reproduction. “The ovary sits at the center of not only the reproductive axis, but also the endocrine axis and the metabolic axis,” Piraye Yurttas Beim, Ph.D., founder and CEO of Celmatix, told BioSpace. Celmatix is developing an anti-mullerian hormone receptor 2 (AMHR2) agonist that regulates the entire 300-day process of follicular genesis. In contrast, current technology regulates estrogen and progesterone, and only affects the last 30 days of the follicles’ function. Anti-mullerian hormone (AMH) is the master regulator that determines the differing rates of decline of the ovary’s various functions. It signals through AMHR2, which is primarily found on ovarian cells. The AMHR2 agonist is designed initially for chemotherapy-induced ovarian failure. After about six weeks of chemotherapy, the cells that make AMH undergo apoptosis. At that point, “There’s nothing to keep the eggs and follicles in check,” Beim explained. As a result, the follicles are activated early. Consequently, the timeline (to menopause) that normally winds down from birth to about age 50, accelerates. “For every month on very high dose chemotherapy, you lose a year and a half of your timeline to menopause. Obviously, that has implications for fertility, but…these women are [also] at significantly increased risk of acquiring diseases of aging earlier in life.” When ovaries fail to function early in life, uterine fibroids, endometriosis, polycystic ovary syndrome (PCOS), infertility and early menopause may develop. “PCOS, for example, is a significant risk factor for mental health issues, diabetes and insulin resistance, metabolic disorder and obesity, heart disease, certain types of cancers and infertility,” Beim said. “It is niched as a reproductive condition, even though it is actually a significant metabolic and endocrine disorder.” Another example is endometriosis, an inflammatory disorder that increases a woman’s later risk of heart disease and stroke. Celmatix’s recombinant, biologically active AMH compound is being designed to add back an activity that’s missing from the body, Beim said. It’s been shown to protect the ovary in animal models that were exposed to chemotherapy. “You can’t experimentally differentiate between the ovaries that were exposed to chemotherapy and those that weren’t,” she noted. “The end of ovarian function during the menopause transition is the single biggest accelerant of the disease of aging for women,” Beim said. Therefore, “Celmatix is developing drugs to optimize the function of organs that are unique to women. This isn’t repurposing something…or targeting estrogen in yet another way. This is doing something fundamentally different.” This AMHR2 agonist has the potential to evolve as a broad platform. Additional pipeline programs will be announced in the coming year. Cyclica: The Long Road to Non-hormonal Birth Control Cyclica entered the contraceptive space as the result of its long-standing relationship with the Bill & Melinda Gates Foundation and its own mission “to advance research and drug discovery efforts in areas with high unmet needs where the industry isn’t allocating sufficient time, knowledge or capital technology resources,” Naheed Kurji, CEO, told BioSpace. A non-hormonal contraceptive has the potential to eliminate the toxicities associated with hormonal contraceptives as well as improve adherence but, Kurji cautioned, “It’s a high-risk endeavor.” A search of ClinicalTrials.gov shows only 24 studies in total that have addressed non-hormonal contraceptives (which includes devices), and only six are funded by industry. Investment in contraceptive technologies intended for use in low- and middle-income countries was only $64 million in 2018, according to Kirsten Vogelsong, a senior program officer at the Gates Foundation. “It’s estimated that more than 225 million women in developing countries have an unmet need for effective contraception,” Kurji said. The Gates Foundation pledged $280 million per year between 2021 and 2030 to develop improved contraceptives that meet the needs of that population, which it lists as being discreet, longer-acting, safe, reliable and under the user’s own control. “We’re working on about ten biological protein targets that have been identified by academic researchers throughout the world….including the Structural Genomics Consortium, Kurji said. “The challenge is that no one biological target has been validated. This is still very early.” Cyclica is looking to design a tool, compound or probe to validate the biology. Artificial intelligence plays a big role in that validation. “We’re able to take a portfolio strategy and unlock things that otherwise would not know if you looked target by target,” he said. Developing a small molecule solution that enables infrequent dosing is Cyclica’s goal. “Milestone number one is to design chemistry that interacts with a target that has functional readout,” Kurji said. “Not much work has been done in this space…and a lot of the biological targets we are working on have zero chemistry associated with them, so there are no previously-established starting points.” That leaves Cyclica working with targets in which the protein structure is unknown or only partially known, where no pocket has been identified for a small molecule drug to target and in which the biology itself may be tenuous. Then it must show function in appropriate in vivo models. The Gates Foundation estimates it may take two decades for a non-hormonal contraceptive to be developed. Univfy: IVF Success Prediction More than 8 million human babies have been born using in vitro fertilization (IVF) since 1978. The process, however, can be arduous with no assurance of success. It’s also expensive, ranging from approximately $20,000 to $30,000 per treatment cycle (which is one month’s attempt). Two or three cycles are often needed to develop an egg that can be fertilized, develop into an embryo and be implanted in the uterus. “There are a few challenges with IVF in the U.S. and globally,” Mylene Yao, M.D., founder and CEO of Univfy, told BioSpace. “The information is fragmented, personalization is important (but lacking) and cost is a big barrier. Only about 3% of people in the U.S. who can benefit from IVF are using it.” Univfy is helping change that with its pre-IVF report. Some IVF clinics now offer a financial rebate program based on that report to significantly defray the cost of failed cycles. The pre-IVF report differs from the usual IVF specialist’s consultation in that it is personalized to the couple and – importantly – to the fertility clinic. “It helps patients and specialists understand the probability of having a baby from one IVF treatment, the number of embryo transfers they may need, and, if that fails, their chances of having a baby if they were to do two or three IVF cycles,” Yao explained. The report is based on AI and machine learning and incorporates the patient’s individual health report and the outcomes for patients with those conditions treated by a specific clinic or physician. Fertility specialists currently are limited to more general data, such as the patient’s age and medical condition and the success rate of the clinic or specialist. “While that data is accurate, it’s not meaningful to any particular individual,” Yao said. The pre-IVF report, however, is 95% accurate. Univfy’s pre-IVF report is available through collaborations with more than 50 clinics in 15 states within the U.S. The company is also working with clinics in Canada and Europe, and will soon launch in the U.K. “We’re seeing a lot of interest from clinics in the Asia-Pacific and Middle East regions as well,” Yao said. Univfy is also expanding the pre-IVF report to include non-traditional fertility needs, such as single women with frozen eggs, members of the LGBTQ+ community who are interested in having their own biological children and older women who may have better chances of becoming pregnant with donor eggs.