Gameto's iPSC Fertility: Overcoming Scientific Challenges

In this Pharmaceutical Executive video interview, Dr. Dina Radenkovic, CEO of Gameto, discusses the company's pioneering use of induced pluripotent stem cell (iPSC) technology in fertility treatments, particularly addressing ovarian aging. Its lead product, Fertilo, is an iPSC-derived ovarian support cell line in phase III clinical trials in the US. The company faces multiple challenges, such as the scarcity of human eggs and regulatory hurdles, with Gameto navigating different regions and their regulatory bodies. Radenkovic also highlights the need for better models to study female-specific conditions and the importance of political advocacy and funding to drive innovation in women's health.

Pharmaceutical Executive: Gameto is pioneering the use of iPSCs in fertility treatments. What are the most significant scientific hurdles you've encountered in developing and scaling these therapies, particularly in relation to ovarian aging, and how are you addressing them?
Dr. Dina Radenkovic: The first problem is that we didn’t have good models to study ovarian aging that causes infertility (including loss of ovarian function, late-term menopause, and unique pathophysiological and medical conditions). A lot of the animal models that we use, like mice or primates, do not experience the same concept of ovarian aging. We decided to tackle that by building iPSC derived ovaries in a dish. We've done that with the sponsor research agreement with Harvard Medical School's Church Lab. We've published research that shows that our ovaries-in-a-dish beat previous mouse chimeric models. We've even collaborated with Johns Hopkins University and the organ transplant unit to receive cadaver organ donor ovaries and linked to primary tissue to truly replicate human biology in our ovaries-in-a-dish. This allows us to develop different treatments and rapidly test them.

That is what enabled us to bring Fertilo, which is an engineered iPSC-derived ovarian support cell line to mature eggs outside of the body, to phase III in the United States. Our trial is available on clinicaltrials.gov and is going to start recruitment at the end of March 2025. We are already clear for commercialization for therapeutic area agnostic and commercial fertility in several large markets like Australia, Latin America, and others.

That was the ovary-in-a-dish model that helped us understand human biology and overcome the first scientific obstacle, which was: how do you develop novel treatments if you don’t have good models to study and test them in the lab?

The second challenge was really around our lead product, Fertilo, which is used for egg maturation. You need to get access to human eggs, which are a very scarce resource. This is why the IVF industry exists.

When we did our first wave of human studies, we looked at egg maturation as the end point. We wanted to see if Fertilo matures human eggs and are those eggs genetically, epigenetically, and morphologically healthy like the eggs that have been matured inside of the body with standard of care IVF. We've managed to partner with RMA of New York (one of the leading fertility clinics in Mount Sinai) and worked with one of their fertility specialist doctors. We worked with fertility clinics around the world to build the largest library of sequenced human eggs to truly show and be confident that our eggs are genetically and epigenetically normal.