Gameto: Addressing Regulatory Hurdles in iPSC-Based Fertility

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 with FDA clearance, and commercial availability in markets like Australia and Latin America. The company faces challenges including the scarcity of human eggs and regulatory hurdles. 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: From a regulatory and manufacturing perspective, what are the key considerations for bringing iPSC-based fertility treatments to market? What unique challenges does this present compared to other cell therapies, and how are you navigating them?
Dr. Dina Radenkovic: We’re the first people pioneering iPSC therapy for use in women’s health and IVF. We’re also the first iPSC in Phase III in the US. When there is no precedent, you’re chartering new waters. There’s an additional layer of risk that we must deal with and successfully manage. Fortunately, we now have designations and we’re cleared to commercialize or are in the final stages of development for approval.

One of the challenges is just determining how this product is regulated. Given that our product is used in a dish and has no action inside of the body, it legally meets the definition of a device. Products for maturing eggs outside of the body (which is called in-vitro maturation) have been approved in the US and across the world as devices. On the other hand, our product is still made of living cells. We had to work with regulators around the world to get the proper designation and understand how to get it approved.

It took the longest to get the designation in Europe because they initially said it was not a pharmaceutical product. We went to get regulated as a device, but then they said that devices are not made of living cells. We just managed to obtain a designation with EMA, and we worked similarly with regulators across the world since our designation differs across jurisdictions.

In the United States, we’re considered a biologic, so we’re regulated by CBER. Our IND that was cleared for a Phase III trial was for a BLA submission. In other places where we are cleared for commercialization, we are classified as reproductive tissue or a device. The different designations result in different times to market for different jurisdictions.

When it comes to manufacturing, we have a lot of benefits. We are only treating a few cells and not the whole body. Some of the issues that present with cell therapy, like immunogenicity, are not as hard to solve when you’re only treating a couple of eggs outside of the body. We have already set up GMP manufacturing to supply the IVF cycles, and that is because of the lower dose compared to in-vivo cell therapies. There’s also a reduced scientific challenge when you treat the eggs outside of the body because there is no immune system.

We’ve partnered with REPROCELL, we’ve licensed the one of the world’s first female allergenic iPSC lines, we created a proprietary manufacturing differentiation protocol, we have our bank that should give us supplies for the next 40-to-50 years, we’ve developed potency assays and batch release criteria, and we can rapidly produce Fertilo vials in a scalable and efficient way.

It was challenging setting it up for the first time in iPSC. There were lots of problems that we had to solve, like figuring out how to fill vials with such a low cell dose. IVF is a great first application of cell therapy because it’s much easier to do clinically compared to in-vivo cell therapies, particularly when it comes to cost, scale of manufacturing, cell doses, and immune rejection.