Dr. Dina Radenkovic takes us to the future

A physician-turned-entrepreneur on how reprogrammed stem cells are transforming reproductive health care.

Gameto, co-founded by CEO Dr. Dina Radenkovic, can trace their origins to donated skin cells. These cells were reprogrammed using cell engineering and turned into an indefinitely available bank of ovarian tissue—effectively a human organ in a dish.

The mere fact that this is possible is enough to astonish most people. But what is even more remarkable is how close we are to using this capability in the clinic.

Soon we will be able to mature eggs outside the human body, which means that fertility treatments that used to require weeks of hormone injections may take just days. It means that hormone-secreting tissue could be re-implanted as we age, making menopause a gentler, more manageable transition.

With a fresh $44 million Series C round to fuel Gameto’s Phase 3 trial, what once sounded like science fiction is quickly edging into reality. And patients across the United States—including those at Maven’s partner clinics—are on the cusp of accessing these new possibilities.

I spoke with Dina about her inspiring journey from scientist to entrepreneur, and how the technology she is bringing to market can open a new era of reproductive medicine:

You were born in war-torn Serbia, and then went on to study math and science in some of the best institutions across Europe. You’ve been a frontline physician during COVID-19, and now a Forbes 30 Under 30 winning entrepreneur. So most basically: what brought you to science?

I describe myself as a builder, and I grew up in a family that was very science-oriented. My father was a professor of embryology in South Serbia, and so I had early exposure.

Where I come from, all human science is considered medicine. Biomedical engineering and biotechnology don’t really exist because the industry doesn’t exist yet. So as somebody who loved doing math, physics, biology, chemistry, etc, medicine seemed like the one and only profession that I could go into that would apply a little bit of everything.

Not all scientists can be entrepreneurs, and certainly not all entrepreneurs are scientists. And yet you are the quintessential combination of both. What made you want to move into the entrepreneurial space?

I fast tracked a lot of my education and moved by myself to the United Kingdom, and then later to the United States.

By being in the U.K., I was exposed to this whole new class of entrepreneurs, and that really happened to me at Founders Forum. I heard about it in my second year of medical school. I had just finished my diabetes clinic rotation, and I got really excited about the opportunity to address gestational diabetes.

In the U.K., when we diagnose gestational diabetes there's only this six week postpartum checkup, and then more than 50% of these women within five years of the verdict developed Type 2 diabetes—even though that type is totally reversible for a lot of people. I started thinking maybe a digital therapeutics program could do something about that.

So you’d never been exposed to entrepreneurs before, but then you come up with this idea.

I told myself, okay if I finish my exams early, I’ll apply to Founders Forum. But then they extended the application deadline so I had no good excuse. I applied.

Fast forward, I ended up as a finalist with some awards in the competition. Founders Forum is really the number one tech event in Europe, and that’s where I learned what venture capital was.

I realized these entrepreneurs were just like me: they're focused on the problem. They like fast paced things. They love science, but they do so many different things, and it's all about the mission. I found my tribe.

Let’s talk about Gameto. I know that the core technology is a spin out of George Church's lab, who's one of the foremost geneticists in the world. Tell me that story.

Okay, so we’ve fast forwarded a decade. By this point I’m a partner at the SALT Bio Fund, I’ve exited my first business, and I still had a research post at King’s College London at the Institute for Research in Aging.

I personally became obsessed with this idea of female longevity. I was like, well, if we keep living longer and not addressing issues like infertility and later on menopause, aren’t we just worsening the root cause of gender inequality in our society?

I couldn’t understand why women’s health biopharma doesn’t exist. And it’s not because smart people are not at all interested, because they are. But the answer is we lack good lab models to test and study the female reproductive system. Mice don’t menstruate, and primates don’t develop menopause like we do.

Hold on. Mice don’t menstruate?

No. Even today, if we’re doing work with rats and rodents on menopause research, we either surgically remove their ovaries or we use a chemotherapy drug and then burn it.

That model can answer certain questions like, oh does this affect their liver? But it won’t actually tell you how the drug affects normal ovarian aging, fertility, and menopause. All women develop infertility and menopause eventually through a more gradual loss of follicles.

Plus, ovaries are very hard to get to. They’re not like testicles. That's why an egg retrieval in IVF is still a procedure done under general anesthetic, and why most women don’t go around saying, yes, please take my ovaries for research.

So the idea of Gameto was that we would take this advancement that Shinya Yamanaka won a Nobel Prize for in 2012— induced pluripotent stem cells—and use this to make human-like ovaries in a dish. Now in our lab we have ovaries of women of different ages, and we can induce different diseases.

Okay, let’s back up a bit. What are pluripotent stem cells?

Basically, it's a cell that is programmed to form pretty much, not every, but pretty much every mature cell of the human body. You take a skin biopsy at one point in time, that cell is converted into a pluripotent stem cell, you expand it into a massive cell bank, and then you never need to have a donor again.

So technically, on our platform we could test how any drug would affect women before women of childbearing age are enrolled for a clinical trial.

Right now, that would just happen with rats, but as the FDA moves towards more organoid testing, that's something that can happen. Now, obviously that's not a great business model in biotech, so that's not the primary thing we're doing, but we leverage the organoids to develop different treatments.

Why would that not be a viable business model for Gameto, if there’s so much widespread concern about how drugs can impact reproductive potential?

Unlike some issues in our category that are just women's health related, this is just that selling technology as a service is hard. If you can leverage the platform to develop assets and sell those assets, that’s always going to be the bigger business.

Secondly, it is easier to get funded, as you know, when you have a lead asset, and then leverage the platform. And then thirdly, if there were more drugs that needed to recruit women of childbearing age, I think pharma companies would care more about it. But also, regulators need to open up conditions to allow more, and I think with organoid testing that will happen. So I'm very optimistic that that is something that we will do in the future, because I think it will enable the whole field.

So you have used your technology to develop a business model that sells your own innovations. One of them, Fertilo, builds off of the science of In Vitro Maturation (IVM). Most of us know what In Vitro Fertilization (IVF) is, but not IVM. What is it, and how are you using it?

We are bringing the world's first cell therapy to women's health, and we're bringing a cell therapy in vitro. So at a high level, right now in IVF a woman undergoes hormonal stimulation and that involves 10 to 14 days of twice a day hormone injections, after which you have to grow eggs.

In vitro maturation means you try to shorten that, and you want to just grow the follicles a little bit and then with a little bit of stimulation or none, you want to take the eggs out and see if they will spontaneously mature, while providing some nutrients and then fertilizing the eggs.

Now, I think anybody who has done a cycle knows why it would be great to avoid two weeks of formal injections, especially given people need to often repeat that several times.

And just to emphasize: not only are those two weeks of stimulations unpleasant, they also make up almost a third of the cost of an IVF cycle.

It’s a big financial cost, a big time cost, and a big emotional burden.

There's so much complexity in bringing drugs to market that support reproduction. Some of it is well founded, and some of it really slows down innovation. I'm curious, what does it look like to collaborate with the FDA on something that has never been done before?

IVF has not had many trials, but the couple of trials that do exist are all for hormone injections. So that helped us set the precedent clinically. Where I think we were having a harder time is, how do you make the product from induced pluripotent stem cells? The nice thing about induced pluripotent stem cells is they’re synthetic, so there's none of these ethical issues.

Certainly, the FDA is the toughest regulator that we have in the world, and they set standards for a reason. I would say, overall though, we enjoy the scientific interaction and have had a positive experience.

Tell me about the phase three trial you have underway. How close are we to an approved, effective form of IVG?

So we're now recruiting. We have sites in all major US cities—New York, North Carolina, Texas, and then Florida is opening up. The first time we will do a readout will be once we treat 250 patients. At that time, we will see, did we reach statistical significance for approval? Do we continue with this trial? What is this trial showing? We've had over four babies born with this technology elsewhere, and the oldest baby is now seven months old, so we’re not worried.

If at that point we have something that is already statistically significant, we may already submit the full BLA for approval. We hope to do that read out at the end of next year, and then we will see.

But if that trial goes well, we’re taking on the market pretty soon, and we’ve seen great interest from patients.

What my team is reading, building, and thinking against:

• To dive deeper into the near future of IVM, this wonderful profile of Gameto in The Atlantic is required reading. As friend of the Preprint Dr. Pietro Bortoletto puts it in the piece, “Right now our treatment options are pretty binary. Either you just put sperm inside the uterus. Or you do IVF, the full-fledged Cadillac of treatment.”
  
  Dina is on the cusp of the first ever alternative — one that would be faster, more affordable, and eventually more accessible.

• My colleagues at Juniper Genomics recently announced $4.6 million in seed funding to commercialize a substantial revision to the way pre-implantation genetic testing (PGT) typically works. Currently, we test primarily for duplicated or absent chromosomes, a controversial practice that is not always effective or valuable in predicting live birth rates. By contrast, Juniper is sequencing the full genome and detecting point mutations that better predict miscarriage. In my view, this would be a major leap forward.

• Male fertility is not a field that has historically benefited from venture capital investment—until now. Our male fertility partners Posterity and Fellow have both announced Series A and Series B rounds respectively within the last year to bring evidence-based semen analysis and urological care into the digital era. These advances promise men and their partners more informed and compassionate paths to parenthood.

• Earlier this year the Maven executive team visited the world’s first fully-automated embryology lab in Mexico City, created by Conceivable Life Sciences at the helm of their visionary CEO Joshua Abrams. We absolutely felt we had stepped into the future as robots precisely manipulated gametes, creating embryos more safely and efficiently than equivalent human operators.
  
  Two weeks ago we learned that Joshua passed away after a long battle with multiple myeloma. He was endlessly curious, passionate, and inspiring. I walked away from every conversation with him feeling a little bit smarter and a little more hopeful. I highly recommend this moving tribute by his lifelong business partner Alan Murry.