The Start-up Making IVF and Egg Freezing Faster and Less Awful

We are in a society where women deserve better solutions. The birth rates are declining, and we think that the right way to solve it is to allow people who do want to have children ability to do so when they feel ready.

Hello everyone. Welcome to another episode of The Kormit Podcast. Memory Podcast. Today we'll be joined by Dina Radakovich. She is the co-founder and CEO of Gameto, and I will be heading into a subject matter that I, I am certainly far from an expert on, which is, which is women's reproductive health and biotech around, um, all of these issues. But, but Dina is, uh, she's pretty remarkable. She's, she's very young. She's a doctor. She's accomplished all kinds of things, um, in her 20s that would, would astound just about anyone and, and has started this company that is doing pretty spectacular things with IVF technology and potentially down the road with, with menopausal technology. And it was something I just felt was undercovered and deserving of attention. And with that, we'll turn it over to Dina. Hello, Dina.

Hi. Thanks for having me today.

Thank you so much for coming on. I feel like I'm going to embarrass myself on this podcast wading into women's reproductive health. This is a field I am actually super interested in. I just wouldn't say It's my forte. So anyway, I hope you will be— you're here to be my guide anyway. So I want to dig into everything you guys do and, and, and your story and the technology is fascinating. And I think maybe just need a little explaining for some people. But, you know, I wanted to start at a particular place where I thought it might be a way for people to understand what Gamido is up to. As I understand it, last December there was a very special baby born in Peru that was really the first one of a big major milestone for your company and your technology. Could you tell us about this baby?

Yes, absolutely. I mean, a lot of founders would say that their company is their baby, but on December 7th last year, that term got a completely new meaning for me and everyone at Gamito. And at Gameta, as you mentioned, we are a company that leverages cell engineering and induced pluripotent stem cell technology. So iPSC, for which Yamanaka won a Nobel Prize. And we take these induced pluripotent stem cells and make cells of the female reproductive system. We use these young iPS-derived ovarian cells to mature eggs outside of the body and change an outdated process of IVF and egg freezing that hasn't changed since the birth of the first IVF baby happened in 1992. 1978 in the United Kingdom. So, uh, what we've had on December 7th of last year was the first baby in the world. It was really a medical first, not just a milestone for Gameto, with iPSC technology, where the eggs of a woman were not matured inside of her, her body fully, but the final step of maturation was done outside of the body, co-cultured with our young ovarian support cells that were derived from induced pluripotent stem cells, therefore mimicking a young ovary in ish, and then leading to that maturation process, after which the eggs were obviously fertilized, months later embryos implanted, and then a healthy baby girl was, was born.

Yeah, and, and we're gonna unpack iPSCs for everybody here in a little bit because it's a topic I'm fascinated in. But, but so the, the premise, a big one premise, an early premise of the company is that you're trying to make the IVF process more convenient, possibly cheaper, and to have some of this, like you just mentioned, this— the maturation of these cells actually take place in a dish and to reduce the number of hormone injections women have to have during the IVF process. And so this was the first— this was the first baby that really bore out all this, this technology that you've been working on for years.

Yeah, absolutely. And maybe to kind of go into what is the current process and why this matters. As I mentioned, IVF, truly a miracle of science, right? Since that year, since Lise Brown was born, over 10 million babies have been born with the technology. I'm sure they're in the audience, so many grateful families to IVF technology. But I also do know that women who have gone through the patient journey have had a very difficult time. And the statistics show that right now to go for IVF or egg freezing, whether or not it's a male or female problem, like I think this is important to mention that yes, like we're altering the female patient journey, but in reality, like infertility is everyone's problem. About 40 to 50% of infertility is also male related. And that is only talking about heterosexual couples, right? Like, even a lot more same-sex couples allow on Science to Build Their Families. So this is really like a, a problem that is affecting us as a society. We're having children later, and more and more people need to access these services. Now, when you look at these services, patient journey hasn't changed. For a woman to mature and get enough eggs in one cycle, she needs to go for about 10 to 14 days, twice daily injections of hormones. In today's day and age, these hormones are still urine-derived from some women, like marketed today in the United States. Or some are recombinant. They cause a lot of unwanted effects because you're giving like hormones to the whole body to act on one own cell type of little tiny ovaries at the back of your tummy, right? So you're kind of acting everywhere in the body. We know that hormones control everything, and to act on women's own support cells, so you're acting on her own, own support cells to try and say, hey, can you mature more eggs? So, and that's only one cycle, right? And then on average, and today in the US, which is one of the highest success rates of IVF in the whole world, a woman needs about 3 cycles for a baby. And let's remind ourselves that nobody's doing and spending all this money and time for fun, right? Like ultimately people do want a baby. So that's where like the, the pain, the physical burden, the emotional burden, the side effects, the risks as well, like really compound and become like a very difficult journey. So what we say, you know, with, with Fertilo is that we really change that. It's a, it's a disruptive technology that is changing this multibillion-dollar hormone injection market and saying like, do we really need this? Why treat the woman when you could treat her eggs? And because our cells are iPS-derived, they're epigenetically young. So you effectively give every woman this young ovary or young follicle, to be more precise, in a dish. So you leverage a little bit of stimulation inside of the body with a Fertilo process. A woman, depending on her ovarian reserve, would still have up to 0 to 2 or 3 injections. And then you then undergo a same egg retrieval process where the eggs are extracted outside of the body, and then the eggs are co-cultured for about a day in the laboratory, after which they're washed, denuded, enzymatically completely cleaned, and then they can be frozen or fertilized. So you— it's kind of like changing like a marathon into a 3-mile run and I'm actually training. I'm registered for a half marathon next week and I haven't done any training and that's already a burden. So imagine like a marathon, whether you tell somebody, hey, can you run like a marathon 3 times? Or, hey, can you do a 3-mile run 2 or 3 times? So like it becomes immediately more accessible, more likely to be repeated. And then all of the unwanted effects mentally, physically, financially as well, hopefully kind of decline as well. And in our studies, you obviously mentioned the first life birth, but Fertilo, which is the product that I'm describing, the program of this for maturation of eggs outside of the body derived from stem cells, as we call it, is already cleared in many markets around the world. We have over a dozen ongoing pregnancies and we actually got clearance. So we are now starting our Phase 3 trial in the United States, which I believe is probably the first Phase 3 trial of any iPSC technology. And this time just happens to be in IVF.

And I wanted to talk about that. Yeah, I saw that it was approved in so many, so many countries already. So the US is just— you can fully do this in about— what was it? I saw it was like 8 or 9 countries, I think. Yeah.

And it's growing. So we have— but it goes around to kind of what is the designation of the product? I think that is where was one of the biggest challenges of running this company is that when you start a biotech or any like, you know, deep tech company, you always start with a premise. Look, like, this is gonna— if this works, it's going to be awesome. I'm gonna help the world. Everybody's gonna, you know, you make the world a better place, you build a great business, but then you start with that risk that you don't really know if it works because you can't really bootstrap and test it in your garage, right? Like, it's not how, how these companies are made. However, you know, an additional challenge of our company was like, okay, even if I make this to work, like, how is this going to be approved? Like, what is this? And from the very beginning, working even with different regulatory experts from different countries and even in the same kind of jurisdiction and the same regulatory authority, they would say, well, you know, this is a device because it is used outside of the body, no action inside of the body. So legally it meets the definition of a device. And then to add an additional caveat I haven't mentioned, but this concept of maturing outside of the body is not new. We did not invent it. Some— it's as old as IVF. Recorded births go from 1991, but there, there are some kind of hybrid forms that have happened even before. Over 10,000 babies have been born with this technology. There are FDA-approved products for this. It's mostly kind of a very much media solution, not a cell therapy like we do. And they were all cleared as, as devices. And then in some places, in vitro practices of IVF are not regulated at all. They're excluded from regulations.. And then in some places, like in the United States, ultimately they've said, look, like, you're part— this is a living cell product, so we will classify it as a biologic. So I think like the time to market and the level of evidence you need to prove in studies to get approved went from, are you completely excluded from pharmaceutical regulations because we just do not regulate in vitro practices? Are you reproductive tissue? Are you a device? Or are you a biologic? And that is something that it really every jurisdiction had to set a regulatory precedent because this is such an innovative product for a lot of them.

And you talked about, you know, part of this is I've seen you give other talks. I mean, this is about this 2-week process of all these injections you usually have to take. Does it fit in with people's lifestyle, how busy they are? You know, it's a lot of work. And so you mentioned already, you know, maybe You have to do 1, 2, 3 injections. You, you know, you also mentioned going because I know people who have done this where they have to go for multiple rounds of these treatments and it gets up to what, like $20,000 if you start.

Sometimes per cycle.

Per cycle. Right. So it's expensive and it just wasn't clear to me in everything I read about you and your company. I got the convenience part, but I wasn't sure if this cuts down potentially on the number of rounds that you have to do.

Yeah, so I think some of these questions are, we're still early in the technology. I can comment on the data that we have, that we have published and that we're about to publish. So there are a few ways of looking into that. So far what we have shown is that with our process, you get about the same number of healthy, good embryos per cycle. Similarly, in places where we are approved, the pregnancy rates are as good as IVF in those clinics. There are some potential signals that in certain patient populations where we actually already know this concept of in vitro maturation works better, like women with polycystic ovarian syndrome, women with high ovarian reserve, egg donors, egg freezers, that this could work better. But I think right now we're still in that early process. We're still collecting more data. What we do know already from kind of doing, and we published that paper in Fertility and Sterility Science last year, for example, about the side effects and the ability to repeat, right? So what I think we're certainly collecting this year is data in specific patient groups to see, okay, like this looks to be potentially more effective in this patient population, let's prove it. And that's the data that we, you know, we don't yet have in robust large patient numbers. But one other thing that you, you, we already can say is that you look at women who've done one cycle of IVF and one cycle of Fertilo, and then the women who've done a Fertilo cycle, 92% say yes, I would do it again. And again, it's only, you know, 2 to 3 days. And so it's about the repetition number, right? Because ultimately you need a few cycles for the majority of people to get a baby. So already from that point of view, you're more likely to get it. And I don't want to, you know, go in detail on the pricing because obviously it differs from one jurisdiction to another. And the final pricing is usually done after approval. And we therefore don't yet have US pricing because we're just kicking starting our Phase 3 trial right now and hope to start recruitment in a couple of weeks. But essentially, current hormone injections are about $4,000 to $5,000, where depending on where you cut it per cycle, and you don't need that many. You also don't need like the clinic monitoring. So we do, you know, believe that this should be a more accessible solution as well in, in, in all jurisdictions where it's launching. So kind of like just from a convenience, side effects, and access point of view, you're more likely to get to that 3, you're more likely to get a baby already. But more studies are currently being in development, and also our Phase 3 trial will also look at our pregnancy rate in the United States, which would be an important data point.

Okay, let's get into some of the science. And please, I'm just a reporter, Dolt, so correct me as we go, but I think Somehow out of the first handful of shows that we've done, we're talking about iPSCs all the time. I think this is like the only podcast that I know of that, that it's following all this this closely at the moment. But so that's these induced pluripotent stem cells. For people who have heard some of our other shows, it's like this amazing technology where, as you mentioned, Dr. Yamanaka won a Nobel Prize for this in 2012. He found a way to take Basically any cell, you could take a, a skin cell off an animal and, and hit it with these, these 4 proteins, this combination of proteins that they call transcription factors, and, and reverse it back to the, the stem cell state. And then we found that then you can, you can mature those cells forward again and, and turn them into whatever you want, a, a brain cell, a neuron, a heart cell. A liver cell. And so in this particular case, you're, you're turning at least some of— yeah, I know you have a wide range of, of areas where the company is hoping to go, but in this particular case, it's ovarian cells, right? I mean, so you're taking— you're synthetically making a stem cell and then turning it into an ovarian cell and then, and then having those ovarian cells do their, do their jobs on the, on the embryo, right?

Well, not on the embryo, on the human.

Sorry, sorry. On the egg.

But other than that, like, you know, you don't need me here. But you've explained it very well. I would say, like, I think honestly, obviously I'm biased, but I do believe this area of cell engineering holds a great promise. We've certainly had kind of waves of hype of regenerative medicine and other, but I do think now we're at the right time where we can see actually the benefits of these technologies, because a lot of scientific major problems have kind of been solved or about to be solved or look like we're getting there slowly. So I think certainly with induced pluripotent stem cells, we are at that place that, you know, they're not embryonic stem cells, they're not human-derived. They can be synthetic, as you say, they can be ethically sourced, they can be mass manufactured. And that is, I think, like a good way to drive the field forward. For example, for Gameto, we've licensed from REPROCELL, a company from Japan, probably the world's first female allogeneic induced pluripotent stem cell line that was fully GMP. And then we took that line and, as you said, converted with transcription factors.

Sorry, what's GMP there? What is GMP?

Well, it's like good medical— it's a kind of a way, good way of manufacturing. So I think that is where we're the highest standard of manufacturing because perhaps in the United States we are regulated as a biologic and our way of manufacturing is regulated like a cell therapy. So more similar to CAR-T cell therapies or other cell therapies, right? So I think that's probably a good way to explain it because every time you have a biologically active product, there are challenges in manufacturing. So those are some scientific challenges that we had to solve to provide. Now we have at-scale manufacturing in the United States and are able to provide, you know, the world's IVF, over 4 million IVF cycles. Now we have, we are lucky that Fertilo is also I would say, an easier way to bring back to the clinic and to commercialize a cell therapy derived from induced pluripotent stem cells. And you might ask why. Well, the reason is because we treat a few cells in a dish outside of the body with no immune system. And some of the remaining challenges from these like stem cells, when they convert into a brain cell or a cell of the pancreas, curing your dementia or your diabetes, is how do you produce enough cells that you can inject into a whole human body not 20 eggs. And then how do you ensure that these cells are then not rejected by the body? Because, you know, they're synthetic, right? They're mass manufactured and they're yours. When again, eggs don't have an immune system, but our bodies do. So I think some of these remaining issues of what they call immunogenicity, that's that immune rejection, but also cost-effective at scale manufacturing are currently being solved for some other programs, and we have a program that is dealing with those issues as well. But Fertilo is therefore a great first application. And I think honestly, it has been a little bit overlooked because everybody went for, oh, like the standard biotech suspects, right? Like the sexy biotech areas. And women's health and IVF was never really scoring there, even though I hope by the end of this podcast I'll convince people it is one of the most exciting areas of biotechnological breakthroughs to happen this this decade, but it wasn't there. And I think that's where we had the first mover advantage, is that even as a small company, we saw it as an opportunity. And obviously, like, me being a woman, I had skin in the game. I understood the problem. I really wanted it solved. I came up with a program idea when thinking about my own egg freezing. I was definitely the target market I was going for at the time. So, um, I think that's why this is a great first wave, and I think iPSCs hold a great promise. But there are still some of these challenges that we have to overcome, although I've seen some great papers come out there about kind of immune covering and other ways. And there are a couple of companies really paving the way for all of us in this space.

No, I mean, you know, not to go super easy on you or whatever, I guess, but yeah, I mean, I was shocked because I've been covering, like I mentioned, iPSCs, especially in the longevity field. There's so much exciting work going on, but, but it's really hard to, to push the stuff from the lab into the real world. And, and there's problems beyond what you mentioned, where sometimes you fire these back up and as a liver cell and it's just kind of overheated and it turns into a teratoma and, you know, starts forming tumors in, in the body. And, and so, you know, it's been a challenge to like you can tell that this technology has so much— I get, at least I get really excited. I mean, it seems like a miraculous kind of thing that we've learned this process of life that we can reverse engineer. And just to— so I was shocked anyway that you were already— I had no idea that not only were you so close in the US on the clinical, the third stage of the clinical trial, but the babies had already been born with some of this technology. And on this point, you know, I mean, Your company, you position it sometimes more broadly as, as almost like a female aging company. And, and this first product is just one of where you're hoping to go. I've seen you talk a lot about exploring where this technology could be used to treat menopause and a variety of female health issues. But I mean, I enjoy how you describe the female aging process as being so different to the male aging process. Can you— could you explain that to the audience?

Yeah. Well, I think the part that you're describing is the way we form our sex cells or gametes, right? That process of gametogenesis. And one could argue that Gameto is kind of changing the playing field of gametogenesis, right? Hence the name. And that is perhaps the main difference that I, you know, I sometimes talk about. And that is that, you know, we as women were born with a finite number of eggs. All the eggs that, you know, we've ever had, uh, were born while we were still in utero. So, you know, there are all these jokes like, oh, I was actually in my grandma's tummy, you know, uh, right? Because I came from my mother's egg that was formed while she was still in my grandma's tummy while my grandma was pregnant. So therefore you're born with a finite number of eggs. By the time you get your first period, you've already lost a lot. And there's variations like different hundreds of thousands, but let's say when you have your first period, you have about 400,000 eggs or so. And then, you know, you, you lose them throughout your life, whether or not they mature. Um, you know, I could lose a few even during this podcast. And, uh, you know, by the time you, you want to use them, you've already have lost a lot. Um, and that time when you want to use them has been changing, right? And the recurrent socioeconomic and demographic factors, I think the, the age of the first birth has been going higher and higher. And ultimately what we have shown is, and what we have found is that yes, it's around the age of mid-30s where, you know, women are super young and every other organ that also declines as we age declines more in synchrony with each other, right? Like our kidney function also declines as we age. If you look at the glomerular filtration rate, the function of the kidney filtration units, it also goes down as you age. And that's why you have age-corrected factors. But you will really start seeing it unless you have some disease from 60, 70 years old and onwards. Whereas with ovaries, you know, you're starting to see a decline in function in your mid-30s and then a complete, you know, stopping of that function around your— the age of 50. Right. The median age of menopause is 51 in the United States. So that's the function, which is, you know, it's a bit odd, right? Like, why are all my organs like aging like this way? And this one is totally aging out of sync think with, with the rest. Like, why are you failing me when I want to use you? If you go back to first principles, doesn't, doesn't make much sense. And I think that's why we said, okay, well, you know, ovaries age faster than the rest of a woman's body. Therefore, women now spend, you know, two-thirds of our lives infertile, and then about half of our life in this stage post-menopause where we do have higher burden of chronic disease, which if you study basic pathways, you can see that some of them are— have clear connections to the lack of hormones that our ovaries produce, right? Like ovaries are an endocrine organ, not just reproductive. So from that point of view, the kind of premise of Gameto is, look, if you know you lose that ovarian function, can we provide you solutions that prevent that decline from causing you harm? And the first version of that is Fertila, which is tackling infertility. And we mentioned why, right? Like it's scientifically easier to do, and we've already kind of got it done. We've established manufacturing, we've proven in large human groups that it works. We published studies, we got approvals, we're in the phase 3. And then you essentially could allow a shorter way for women to freeze their eggs, access fertility preservation, or access reproductive care. And there's now compelling data, and more and more data is coming, right? Like egg freezing is also a new technology, but there's more data that the age of when you freeze your eggs is basically kept. So let's say I freeze my eggs at 28, like late 20s are, you know, for a lot of doctors, a good time to freeze your eggs. And then you want to use them at 38. If you're healthy, if you exercise, if you don't smoke, you know, you look after yourself, you could have the success rate of a 28-year-old because that's when you froze your eggs. Like the uterus, the womb does not age like your ovaries. So that kind of is a great way to allow you maybe 6, 7 more years to reach both your family goals and everything you, you want to have. And there have been numerous studies that shown that a lot of women, even those that do become mothers, run out of time. That, you know, they don't reach their, their family goals. And I, you know, it's very easy to understand why. So I think that's for Tilo. And then beyond that, we look at, okay, menopause. And early menopause, the condition called primary ovarian insufficiency that affects about 1% of women is, you know, what happens during that menopause transition. It's a very brutal reduction in all the hormones your body has been using to make. 8 out of 10 women report some symptoms during perimenopause and menopause, like hot flashes and brain fog. And then some minority experience more severe broad mental health, physical health, sexual health symptoms. But then later on, it can lead to bone decline, it can lead to vaginal dryness, it can lead to pain on urination, it can lead to increased risk of cardiovascular disease. New, new papers suggest even a link with dementia. So then you argue, okay, like, is there something— right now there's this hormone replacement therapy that still kind of, um, doesn't have too much data on. It is probably the best Band-Aid that we have for a lot of people, but we can certainly kind of do, do better. So the idea with our second program, which we called Amino, is where we leverage the same cell engineering technology, but we're basically making an implant like a— that you would put on your arm or a vaginal ring that can provide real-time hormone replacement that you need and therefore delay some of these symptoms and chronic disease that occur during menopause that you could wear for a few years and delay that. And potentially, you know, this is still very early, delay some of the symptoms that come with age and the onset of these conditions. And we have secured some funding for that program and are doing now animal work with the first prototype of the implant. So hopefully, you know, we've started some of the IND enabling studies for Phase 1. So it's a much earlier program, but obviously could have an even bigger impact potentially on kind of the health of women globally, right? Because not and the conditions that affect every woman as they go through menopause, if they, you know, feel that they want some medical treatment.

Is that— and is that iPSC-derived as well, or is it just a totally different—

Everything is iPSC-derived. And the nice thing is that with a lot of things that we've done with Fertilo development, we have already solved a lot of things like master cell banks, a lot of things, right? Like, okay, what are good standards of manufacturing? Even a lot of things that we had to patent. I mean, being the first mover anywhere in an area is very painful. It's very painful because there's very little precedent and it's hard because you have to figure out your own vendors and then vendors don't even know, okay, like what is considered truly like highest standard of manufacturing for these stem cells? And then you're like, okay, I need like a robot and a way to fill my vials. But like, well, nobody has filled the vials with stem cells at this low cell dose. So we have to make our own way of doing it. So we've actually ended up The nice thing is that at the tail end, you have a lot of these know-hows and a lot of patents and IP that you've created, honestly, as just as a byproduct of trying to solve and get your product down. So our manufacturing team has been very, very busy and has managed to solve some of the hardest problems in iPSCs because we just had no other way. And we can now leverage some of that for other programs once they go to a larger clinical scale. Right now, as I mentioned, we're just doing animal work. Work for AMINO. So it's a different—

So for— with AMINO, I mean, what sort of cells are you looking to create in the lab?

So if you look at kind of what we call these ovarian support cells, right? Like, I mean, my dad is a professor of embryology and histology, and he'll probably get a heart attack if I call them all ovarian support cells. But these are different types of like granulosa, theca cells. But ultimately, like, you know, in our ovaries we have eggs. And we have these support cells and these support cells broadly, very broadly. Sorry, Dad, do two things. One is they help eggs mature, right? And that's why you leverage for Rotilo. And then the other thing, they secrete the hormones, right? So estrogen, progesterone, like androgens that we also make as women that affect our drive, lean muscle mass that we also lose post-menopause. These are not made by the eggs. These are made by these support cells. So Or Amino, you could argue, leverage that second function of the support cells. So you leverage kind of the same support cell technology. It's just that because you're putting them inside of the body, you cannot just inject the cells, right? Like it's not kind of how it's going to work. And you want to ensure that they're— so we have an encapsulation method. Then you want to ensure that they can obviously not escape that capsule, that they can be taken in and out at any time because these are hormone-producing cells, right? We know that that was a problem with some of the HRT hormone replacement therapy studies before. And often the reason why women don't go for hormone replacement, they say, well, you know, I'm worried about the risk of breast cancer. So it's a common cancer, right? Like if you, you know, live long enough, 1 in 9 women, you know, happen to develop breast cancer. So you want to ensure that if you're at risk or if you're worried of anything like that happens, you can always take it in and out. Also that you have that choice, right? Like I don't— that, you know, you think Okay, I need this therapy to go down, push this onset of menopause, feel good, keep my lean muscle mass, keep certain parameters well, and then you can taper down. So it has to be taken in and out, but it also needs to be able to release the hormones so that they can provide that real-world replacement. So it's an encapsulation of the cells, and then we'll actually leverage some of the technology of the contraceptive devices. So we kind of use very similar model because that has been proven, it works well. So we kind of use some of that too. And that's how we've made the first prototypes that we're testing in animals. But then again, obviously, as you know, in IND enabling work, there's obviously depending on experimental data ability and to change and iterate depending on the results you get. So I think like we're hoping to build an implant like a ring or like an implant that you can put here in an arm, take in and out, provides real-world hormone replacement. You don't have the negative consequence of menopause. You push away these conditions that come with aging, like osteoporosis, so forth, for a few years, and then you could stop wearing it. But you've kind of got, again, a few more years in a more gradual transition, not like an abrupt transition that you lose 80% of hormones within a year and you don't, you don't feel good, which what a lot of women report.

Okay. What I've seen— I'm going to— all right. This is where I have potential to embarrass myself greatly. What I've seen you talk about this before, you mentioned that I believe this is what you say. Humans are unique in experiencing menopause except for 4 whales that also seem to go through that. Same process. I always see you throw out this fact, but I was so fascinated as to like how we know this and why we think this is.

Yeah. So, I mean, I had the pleasure that I spent some time at the Buck Research Institute where I had the visiting research scientist post and I worked closely with Dr. Jennifer Garrison. And I'm a doctor, like I've only studied humans. I've spent like 6 months doing little humans and that honestly already felt too weird. So I have not studied these whales nor animals, nor checked personally. So I just want to protect myself there. However, the work that Jennifer, Dina, and Mira also at the Buck Institute right now are doing and what they report, and there have actually been some follow-on studies, but so far we've shown that other similar animals do not develop and experience ovarian aging the way we do in humans. I think that is what we do know. Evolutionary biologists say that it is really only humans and these 4 types of whales Some studies have reported— this is a newer paper— that certain primates in captivity would develop menopause, but they don't know if it's the captivity that causes it and just a different way of life that's more similar to human life, or is it that like in wildlife we never really caught it. So I think there is some kind of measuring and other variables.

That's what I kept wondering, is like, who's measuring this?

Yeah, so it's a bit difficult. However, I think like what we do know is that animals that we routinely test on, on and study do not have it. I think that is very important because not only that women's health has been perhaps a neglected area for some other reasons, also like if you look at other therapeutic areas where you don't have good animal models to study and understand the disease, and when you have, I mean, models in the first place, right? Like if you don't have good ways to study and test things, you won't develop things that work. Look at examples of pulmonary fibrosis, right? Like it has been a graveyard for drug development despite billions of dollars being injected in the biggest companies companies competing with, you know, very little ultimately changing. Why? Because it's a very, um, the way you kind of induce it often in animals, at least in the early days, um, science has advanced, but in the early days would be you take two layers of the lungs, the pleura, right? And you burn it with a chemotherapy drug and you say, how can this is fibrosis. So similarly for a lot of these, like, of infertility menopause testing, what you would do, you would take, um, mice, you'd burn their ovaries with a chemotherapy drug like Dr. Rubinstein and Van Christen, and you say, okay, they're infertile, they don't have ovarian function, they're in menopause. So that's not how majority of women will experience infertility and menopause, right? Like, some women will after intense whole body chemotherapy, which is why there's this whole concept of pre-chemotherapy, um, egg freezing, fertility preservation, particularly for, for young women. However, vast majority of us, it's, it's a more gradual, uh, decline, right? So I think I think that concept is more similar for that is that look like what is, and also that it's odd and maybe that it's not necessarily even a biological imperative. I think that's the other way why that fact is interesting. And because it's so bombastic, like humans, 4 types of whales, I think it just makes people interested to read about the topic.

I was fascinated. I just wanted to know more. Yeah.

And there were 2. I think there's one that the age of menopause is associated with women's life expectancy. Again, not causal necessarily, but associated. And there were some reports, and I think this is, um, and again, like, I, I, it's not something that I have myself personally tested, but there are some reports that the age of menopause of your sister, it could be associated with your own life expectancy as a man, right? So I think those are some of these things that just show us how interesting this area of ovarian aging is for studying aging as a whole, um, and how potentially by looking at ovaries, because they age so much faster, we could potentially kind of come to some important insights about the aging process in a more time-efficient way. So I think scientifically it's very interesting, but obviously in the company we're very much focused on products that we know we can develop in a timescale that works for companies and test and bring to market, but the whole field potentially holds a lot more answers and that could be helpful for us.

Yeah, I wanted to ask you about that because I'd seen you mention that before. The— if ovaries— yeah, if they are aging at this accelerated rate where, where with almost all these therapies we want to test on, on people, you know, it's one of the huge problems of the aging field is, you know, you don't want to wait wait 70 years for, uh, to test the therapy to see how it's, it's working. Is— yeah, I guess obviously people have known this. Is this just your sort of typical case of, of women's— women were placed, you know, further down the— we just haven't spent as much time looking at this as we should have because people weren't interested enough in women's health? Or, or why have we not, you know, been studying this, this, this organ and this phenomenon more closely?

Yeah, well, I think I'm not so much of a speculative person. Why haven't we? I think, like, it's just like, if something is worth doing, let's do it. That's more of my approach. But I think ultimately it also goes like, where was an easy way to test it? Right? Like, it's a scarce resource over Israel. Like, we're talking about that. You go through 2 weeks to get a couple of eggs out. You want to maximize them as much as possible because because, you know, per cycle you have about 1/3 of a chance of getting that baby. So I think like, and ovaries are not easily accessible, right? Like to get sample from, it's not like getting a skin biopsy. So I think like we just didn't have the primary source. And that's why I think with some of our technology where you can have a full lab of totally synthetic iPS-derived human-like ovaries, and we have shown that these ovaries beat previous animal chimeric models. With some primary tissue as well. We had a collaboration through one of our scientific advisor, Professor Phil Georgian of Johns Hopkins, where certain organ donors who obviously ovaries are not transplanted between humans, right? Like a heart or a liver could save another life, but ovaries were not. So we had the program that we were studying these ovaries to look at, okay, like are these iPS ovaries sufficiently similar to different ovaries from humans? We've shown that they are, and we can kind of look at the ovaries of different ages. So we do have that program, which is their third kind of platform program that we call the OVO, where you really can kind of build a lot of different ovaries. They can live in the lab for, you know, a lot of— a few months. They can— you can use them to rapidly test certain things. You can induce slightly different age of the ovary. So potentially it is something to test. I think certain skepticism perhaps comes from where people say this question, oh, well, how many drugs have translated from ovarian biology into kind of broad medicine? Like, it's more likely to come from certain other animal models. That's a fair argument, but, you know, it also doesn't mean that it won't. There are some studies in academic centers now looking at certain therapies that have some speculation for aging to potentially look at in ovaries. I think it's at the place where It's a very interesting concept. Nobody really knows if it can, but yes, is it an interesting area of study? I believe so.

And okay, I want to learn more in the time we have left about your background. Before we do that, one last question along these lines, just of stuff that I caught that you were talking about. I saw you say somewhere that women were not were not required to be included in clinical trials until 1993. And I mean, is that— obviously, I guess that's true. I mean, it just seems so stunning to me.

Yeah, well, that is with NIH-funded trials. And yes, that is correct. And I think with animal research, I believe female mice were not required to be included in clinical trials, I think until either 2011 or 2016. That's why I need to check. But we're definitely talking the 21st century. Country. And so I think, yeah, that's the reason why I think it's the most exciting area to be in, because you're talking about a TAM, a total addressable market, of half of the population. And there's so much low-hanging fruit when it comes to basic biology because we haven't studied it, right? Like when I first went into med school, I was thinking maybe I'll be a cardiologist. And since the Framingham Heart Study and all of the beautiful double-blind RCTs and so many therapies is like, it's very hard to come with new treatments. You see that novel treatments in cardiology are looking at gene therapies for your cholesterol synthesis and small RNA. Like, it's just very hard. In women's health, like, you could just go and look, this is one pathway that's known. We know what it does. It's not drug. It's easy to make a molecule. It could work. Like, it's a lot easier to get lucky. I think in biotech, you always need to get a little bit lucky, but it's a lot a lot easier to get lucky. So I think like now we're in this golden age of women's health biotech because it is one of the most exciting areas to, to be in. And honestly, like, I think Amita is just at the forefront of that and is going to start that wave for people to realize. And if you look at, for example, obesity, nobody cared about it, you know, even a couple of years ago. People felt like it's not an area that could be solved pharmacologically, and now it's one of the hottest areas because people catch up So I think similarly that's going to happen with women's health. Just understudied, apply like existing clinical and scientific methods to the half the population has not been studied. And there's so much catch-up work, develop therapies that work, you know, translate, scale them. It's a very simple model where you can derive value and I think make a lot of money.

Well, and, and the, you know, you use that word that they, they were not required to be clinical trials. I mean, so were they just not— yeah, I mean, they must have been using some female mice.

Yeah, it's hard to go when there's no requirements in recording. I think if you look at— and this is perhaps a homework for both of us— to look at, you know, what percentages were women in some of these research studies. And usually if you look at, it's below kind of 50%, and I think It's just about like, you know, you should study treatments in populations that you're going to treat, right? Like, this has nothing to do with anything else. It's just like you want to ensure that the study and that paper you're reading as a doctor includes the patient that you're going to treat so that you can leverage some of that knowledge and results from the trial to make your clinical decision and advise the patient on whether— what they should do ultimately. So I think like some of it comes from the fact that obviously, like, when we were worried about pregnancy, and there have been, as you know, like, drug scandals of extreme harm of certain medications causing harm for newborn babies. So that could have also, you know, played the role certainly about like, where do I feel like more cautious about experimentation? But I think right now, and certainly like, that's another potential use case of our DeOvo ovaries, right? Like, before you test, you know, enroll women in clinical trials, particularly of childbearing age. Like, you could test it in like ovaries and look at, is there something ovary-specific, human-like, that I should be aware of before I test it on a human being, right? And right now, I believe you do kind of generation of rats and you see if they can reproduce. So you would do an animal reproductive toxicology study, but potentially in addition, you could do this, right? There are certain ways where you need a whole organism to do certain kind have, um, kinetic studies, right? Like, where does it go? Does it deposit in some organ? Does it deposit in the liver or the spleen? But then there are certain ways where you want to kind of look at the, the, the actual organ itself. Is there something that it will cause? So that could be an added layer. So I think ultimately, historically, women were less studied. I think that is a broadly true statement that we can agree on without knowing the percentages of women in every clinical trial that's been conducted. Um, and there Therefore, you, it's, you know, if you can do the catch-up work, study and bring a lot of value and a lot of suffering for a lot of conditions from infertility to menopause to endometriosis, polycystic ovarian syndrome, and a couple of others.

Okay, that was helpful. Thank you. Just to go over your background a little bit. I mean, I think you were, you're, okay, well, I saw you were on the Forbes 30 Under 30 list. That I'm sure is very exciting. It must also be frightening as well. There's, there's a strange track record of, of people on that list. Do they, do they prepare you for that?

Well, I mean, I mean, I think like it's a, I don't have much to comment on it. A lot of people, I feel like do basic math of like, I, I think they name quite a, actually lots of people on, on, on like 30 Under 30 and there's a 30 on each list and how many years have been going and you can name like, but like 5 or 6. So actually it's a small percentage, so it doesn't bother me a lot. I just go back to the math.

I was just, I've just turned into a bad, bad, bad joke.

I would say it was a good coverage for the company in general, at least for us. Like a lot of people that afterwards reach out being like, oh my God, wow, I was just thinking about doing IVF egg freezing. I'm really excited about your solution. So overall for us, it was a as a positive. And as I said, 66 is small, so you're more likely to, you know, fall on like a banana or get hit by a bus. And I still go out on the street, so it's fine.

And you were, I think you were born in Serbia or grew up in Serbia, right?

I was born in Serbia. Yes, in Serbia.

And then you got your degrees and your medical degree in the UK. You mentioned your dad. It sounds like he was either a professor or a doctor as well.

Yeah, I mean, he went to medical school but then stayed in academia, so did not practice medicine. And he is a professor of histology and embryology in Niš in Serbia, my hometown.

Oh, so he's still in Serbia. So, but obviously, I mean, this field roughly, I mean, is— you grew up thinking about some of this stuff.

I indeed did. So I went to the lab. Obviously, they had some slightly less technical equipment than there is in the US and the resources here. But they were— I was looking at microscope, I was looking at placental tissue and villi. That was his first— that was his main dissertation project. So I was definitely fortunate to kind of grow up in a lot of science background in embryology. And then ultimately, as you say, I ended up in a similar field. My mom is an entrepreneur and my dad is a a professor of embryology, and I'm technically an embryology entrepreneur. So very much, you know, a mix of the two.

Yeah, absolutely. And then, yeah, I'm always curious about doctors who really lean into being entrepreneurs. I mean, it just seems like you've already made such a huge commitment to your studies and all the tests and the effort to get that degree. And obviously it's not like you're going super far afield, and I could see how maybe even, you know, you probably think, um, could help even more people this way. But it must be a difficult decision on some level to, to go so hard into the business world after you've, you've gone so, so worked so hard to get that degree.

Yeah, well, I mean, as if you look at— that is true, um, and yes, um, certainly it was. And there are certain perhaps areas that you miss from clinical practice But on the other hand, again, like, I don't, I'm not an outlier there. I'm an outlier in many things, that one not. Because if you look at, for example, all biotech, biopharma, even like mainstream pharma CEOs, most of them are like MDs that have done medical training, worked for like a couple years and, you know, not like the whole product and went into the industry and ultimately ended up there. So I think a medical degree is, I mean, a lot of people say, well, you know, now ChatGPT knows more than you and what were you doing just memorizing books? But I think, I think it's a great degree that prepares you for a lot of things because ultimately you study humans and a lot of business is making human relationships. A lot of hiring is doing exactly that, like trying to understand like how does this person work? How do they work under stress? A lot of business is forming relationship of trust, which is very similar to what you would do in a patient consultation when you try to form trust in like 15 minutes with someone who's never met you before, and they're about to tell you the biggest secrets, some things that they perhaps are themselves embarrassed of. So I think like some of these things are actually very helpful. Another element is just brutal hard work. Like med school is not easy and nobody cares, you know, like they're like, yes, these are— this is anatomy and you gotta know it by tomorrow. And I don't care if you don't understand your book, like go and do it and you go figure it out. And I remember the first time I read Gray's Anatomy for Students. It's not even original one I have in the background is the For Students, but also is thick, just more diagrams, slightly less text heavy. And I was like, I don't understand any of it. And then, you know, 4 weeks later I was like, oh no, I'm a master. I was doing like my cadaver dissection, pointing everything. So I think that those are just good skills to have in life. And that's why med school is good. Like it's hard work and you learn a lot of things. And I think it provides you with a good understanding of like holistic human biology, what patients want. I also practiced as a physician for a little bit. And I think those things have made me a much better biotech CEO because ultimately what am I trying to doing? I'm trying to build things that will ultimately help patients. And if I don't understand that, I feel like a lot of it can be missed. So yes, like it is a step up, but I feel like it's a natural one. And for me, it was a better decision. And I like kind of things moving really fast. I like the daily challenges. I like I like the different type of challenges that I face. I like the basic science angle, working with people, and I have enjoyed learning about the business angle on the job over the past decade for sure.

It's a fascinating story. I mean, you've done, we'll put some show notes, you know, along with this, but you, we haven't even had time to get into like all the things you've accomplished in your career and your 20 is, is quite staggering. Um, just, just to close out, to give people a feel for where your company is going and, and the big picture, um, you know, we outlined your current product and, and then the one that you're trying to develop around menopause. And, and I, you know, I just didn't have a sense as to, um, is this going to be a company that you think just has many— or I, you know, I don't know the number, but like several therapeutics aimed, aimed at women, or, you know, are these first two products really the anchor and those are meant to be these giant, giant businesses? And I just didn't— I wanted to get a picture of like where you think all this, this goes.

Yeah, well, I think like right now we're a small, nimble but very mighty team. I always say that a unicorn is built from and by unicorns. And I think like I'm very fortunate that I have I have a lot of really great motivated, hardworking colleagues on my team who are all unicorns. And right now we're laser focused to get going with our Phase 3 trial. The information about specific sites, we're going to be at 15 different states in the US starting to recruit. That is an incredibly exciting project. The biggest undertaking we've done as a company. We're also working through providing Fertilo to the places that we are clear to commercialize where there is a lot of interest. So we're now available, so for interested patients in Australia with Virtus Health IVFA, which is one of their largest clinic, you know, top 5 largest clinics globally. We're looking to expand across Asia Pacific, Latin America, and certain Middle Eastern regions next year. So really kind of trying to do the final clinical development as well as early commercialization and strong post-market work of Fertilo. We think that in itself is huge. We're looking currently for partners in Japan because we are in a society where women deserve better solutions. The birth rates are declining, and we think that the right way to solve it is to allow people who do want to have children ability to do so when they feel ready. So I think that's where our solution can help. And so the priority for now is to to get that going inside. Obviously in the company we are advancing the menopause solution. As I mentioned, we have our Logbloq, our other platform for ovarian health, ovarian disease testing. A lot of it is now kind of just in the lab itself. We certainly will be opportunistic if new opportunities arise, but are kind of sequencing different programs and currently funding these two to advance to the clinic to ensure capital efficiency. And then we'll see where things take us. I think like we a lot on our plate right now. And I'm really, really excited. I mean, like, to see Fertilo change lives and the amount of interest after that first, like, birth, it has really been insane. And I think that's where we really want to meet the demand and bring it safely and appropriately into hands of people who want it and need it and cannot wait for it as an easier way to build their families. So that's our focus, uh, for, for next year and probably foreseeable future.

It seems like, like plenty to do. Uh, thank you, thank you so much for your time. I feel like I, I learned a great deal, and it's, um, it's just, it's like amazing to see, um, really like the progress you made in a relatively short time. And, and as a— I don't know how I ended up as PSC nerd, but here I am. It was really exciting to see what you've done with the, with the technology. So thank you. Thank you so much for your time and, and, um, definitely, you know, keep us posted on, on how things go.

All right. Well, thanks so much for having me. It was a pleasure chatting with you.

Core Memory is hosted by me, Ashlee Vance. Our guest today is Our guest today was Dina Rudegović. The show is produced by me and David Nicholson. Our theme song is by James Mercer and Jon Sortland, and the episode is edited by the Jon Sortland.