First in Human Episode #20 featuring Dr. Dina Radenkovic

Sitting down with Dr. Dina Radenkovic for episode 20.  Find out what the CEO & Co-Founder of Gameto had to say about chat GPT and what it could do for healthcare in the next 12 months. First In Human is a biotech-focused podcast that interviews industry leaders and investors to learn about their journey to in-human clinical trials. Presented by Vial, a tech-enabled CRO, hosted by Simon Burns, CEO & Co-Founder & guest host Co-Founder, Andrew Brackin. Episodes launch weekly on Tuesdays & Thursdays.

Simon Burns: Dina, thank you for joining us on First In Human.

Dr. Dina Radenkovic: Thank you so much, Simon, for inviting us and for working with us at Gameto.

Simon Burns: Of course. Gameto is a very interesting mission. You guys are doing some fantastic work. Maybe tell us a little bit more about what it means to redefine female reproductive health and the great work you guys are doing.

Dr. Dina Radenkovic: Thank you. So, basically, at Gameto, we’ve clarified that the mission is to redefine female reproductive health by developing therapies that improve lives. The big problem there was that, women, we start making our gametes [our sex cells] while we were still an embryo. So these gametes or the eggs as we call them. We have a finite number. We start losing them throughout life.

We’ve already lost quite a lot by the time we get our first period. Our ovaries, which are the organs that contain these eggs keep aging at a much faster rate than the rest of our body. We end up with reproductive aging that is much faster than the rest of our body. It happens at the pace. And then we express certain symptoms throughout, right? We first develop in functional infertility that occurs in women already in their early to mid-thirties, and then later on, menopause and all the conditions that occur during menopause.

And we’re effectively patients from the time we get our first period all until death. And there has not been a single company that is really providing treatments for women throughout their journey, right? Throughout their reproductive aging cycle and dealing with the consequences beyond that. The second thing was that it is providing treatments that actually are developed by women for women. I often say that if you just take a man going through an IVF cycle, which I mean if a man has male factor infertility, women are often gone through IVF.

And if one pharma per man would’ve gone through that cycle, they would’ve changed it. They would’ve come up with better solutions. We give these type of injections still to women that haven’t changed for over 20 years. Fundamentally, we believe around developing medications that will have more precise and different mechanisms of action that will try not to disturb or already delicate hormonal cycles.

We think the conversation around fertility, which is the first application of our cell engineering technology is in the assisted reproduction IVF/infertility space. That is an incredibly exciting field to work in. For example, if you take the UK, where I’ve done my medical degree, egg freezing has increased tenfold from 230 cycles in 2009 up until 2,400 cycles in 2019.

One in six couples suffer from infertility in the United States, but, only 2% of babies are born by IVF. It’s one of the very few fields where we can have, very high growth, that can double or triple within the next five to ten years. Even if you look at metabolic disease and pre-diabetes, no matter how many Dunkin’ Donuts you sell, it’s unlikely that we can double or triple it because we’re not reproducing at that pace. There’s not that many people.

However, IVF is a fast-growing field. For women, as we are the current socioeconomic and demographic factors, the fact that the age that women gets her first child is the age of 30, we are balancing careers and many other things at the same time, modern women will want better control over their timeline. If men can make sperm throughout life, why wouldn’t women have the opportunity to do free, cheap, convenient, without major side effects, affordable egg freezing, just to have it as an option, to get more control over their timeline?

That’s the big mission around women’s health. Solving the conditions that a lot of them don’t even have first line medication, following women throughout the trajectory, building that relationship, that trusted science-backed brand providing treatments for women throughout their life. Then initial application on infertility, given that is this fast-growing field, that is really, not fit for purpose, is rapidly evolving. We can use that it’s still embryonic, no pun intended, as a smaller company, try to make significant big wins to allow us to tackle some of the other things that we’re excited about in the future.

Simon Burns: We’d love to double click there on your first product Fertilo. Tell us more about what it is, what it does, and how it compares to some of the fertility treatments in the market today.

Dr. Dina Radenkovic: A lot of our other science with Gameto was done in stealth with the Sponsored Research Agreement that is still ongoing with George Church’s lab at Harvard Medical School. Some of the work that we’ve conducted there, we have published. We have certain things, the bio-archive, a few more publications coming up in the next couple of weeks.

But really is that we take stem cells, engineer them into different cell types of the reproductive system. We built the first stem cell derived organoid reproductive system. We use a specific engineered ovarian supporting cell line to derive a biologic treatment which we [00:05:00] grouped under a unit in Fertilo which essentially mimics what normally happens in the ovaries.

 Normally in our ovaries we have ovarian supporting cells. They mature eggs and they produce the hormones that control our cycles. We replicate what normally happens naturally in a woman’s body, but we do it in vitro. For a full in vitro fertilization, you get a more in vitro experience. We take out that woman’s bodies are essentially part of this lab setup. We try to do it more in a dish. We use our product to mature a woman’s immature eggs in a dish and also improve the quality of a woman’s eggs in a dish.

We increase the success rate, the yield, of the current assisted reproduction cycles. We can reduce the number of cycles, and most importantly, we can reduce the need for the hormonal injections that women get. People often ask me, “Wait, why do women need hormonal injections? Why do you need your drug? Or, why do you need your treatments? Why do you need your media? Why do you need injections?” If you’re taking women’s own eggs, you’re not making artificial eggs.

The reason is that the extraction process for men and women is very different. Men do not require proprietary medication. Their extraction tends to be quite easy. Whereas for women, we do require, a series of medications in order to get eggs, more eggs, mature eggs out. And the extraction itself is still a lot more invasive. It is still something that you’re given a general anesthetic. You have a needle that goes through your vagina to both ovaries to extract the eggs.

So we cannot change the procedure because anatomically our ovaries are at the back of the abdomen. What we can do, we can cut down all these hormonal medications that cause quite a lot of side effects starting with mood swings, inability to do daily activities, sports, things like abdominal bloating, distension, constipation, and then later on ovarian cysts and, a disarray of things even in the mildest form. And, obviously, carry some of the other side effects and increase the cost and inconvenience.

 Making it as short and easy as possible for a lot of women. Reducing the side effects so that more people can access assisted reproduction, which seems to be a trend if we’re going to tackle the infertility problem.

Simon Burns: You guys have been very successful, in fundraising. Give us a sense of lessons learned throughout that process. And if a young biotech founder approached you to raise their first capital with a new therapeutic, what would you advise them?

Dr. Dina Radenkovic: Yeah, so firstly, I would like to acknowledge that we’re in a different fundraising environment than in a fundraising environment which Gameto was raising. Founders raising right now probably don’t have that much to learn from me and they shouldn’t listen because frankly, there’s very little I can tell them because there’s much less external validity. There’s a lot less that can be passed on.

However, if I was to guess what could be useful advice. I would say, especially in this market, try to build a long-term relationship with a few specific investors who you think are likely to be interested in your venture. You make these people invest and they get invested into the project even before they’ve actually deployed capital. If fewer deals will get funded, you try to get them committed, invested, and you differentiate your company from all the other companies that they could fund. 

Proof of concept is always very important. Obviously that is much easier in technology than in bio. In bio we often have to start with the idea because, guess what, proof of concept is at least a few million dollars. Another thing that is very exciting there in biotech is that you can often start from building your case from already approved research. Finding what was the research done all over the world with some research grants. Finding previous papers. Look globally

We’ve learned lately, just mapping out the system, there’s so many places where there was one good scientist, there was some government, funded grant.. And then, it was paused. The company never formed. A lot of this could be put together to at least make a case that what you’re doing is scientifically plausible. Therefore it is a scientific hypothesis we’re testing as you do in a round.

Seed funding still seems to be relatively spared. Although it is a much more difficult fundraising environment. I think it’ll be harder for all of us. You’ve recently raised a round led by General Catalyst. Congratulations. Maybe you have some thoughts to share in your podcast. But in general, seed round funding seems to be relatively sheltered from the wider picture. The final thing, I think it is really ensure space for your partners.

 Be reasonable when it comes to all the terms. Find the people, invest in those relationships, make them commit even without committing capital. Focus on building the scientific case from the resources that you have or that have already been done if you don’t have the financial resources and the setup to do your own proof of concept. Then, get a little bit to get going and ensure there are a lot of good players and that everybody’s got a chunk of the pie.

Simon Burns: Is it right that you guys are not even two years old yet?

Dr. Dina Radenkovic: Yeah, something like that. [laughs] 

Simon Burns: Tell us more about that. Hyper speed is not typically something that people used to describe biotech, but something about the culture that Gameto has, operates at an accelerated pace. What is it about the culture you built that enables that?

Dr. Dina Radenkovic: I would say that it’s too early to celebrate any success. Retrospectively, there are certain methods that worked back then for us for a specific period of time. The same methods won’t work for the next phase of the company. We change as a company very quickly.

 We had one period from March until August. [00:10:00] Then from August up until now, we’ve learned a lot. I was so happy that at our meeting, just recently, everything that we’ve done in August, we were so naive. So it’s that rapid growth. And for different phases you need different methods.

 The one phase that we could isolate where we did have high growth, high execution, rate and we’re, hitting our milestones in advance, was certainly that period last year for which we now have enough data to guess reflect on. Some of the methods that I could isolate there, that worked very well for us, I was very, rigorous on the fully in-person company in the office.

 Now it seems so normal, right? Most people are coming back to that. But if we think about the Q1 of ’21, it wasn’t so much the case. A lot of people told me that I would not be able to recruit talent because everybody wants to work remotely. I had people being, like, “Oh, but I want to work from two weeks in Miami.” And I’m like, “No, this doesn’t count as two weeks in the company. It’s not how it’s going to work with all the trips.”

 It might be more difficult to hire people, but I need to hire maybe 15 people. I don’t need everybody. It’s not like I’m building a country. I’m building a tiny little company. I do want to have those evolutionary pressures in those selection criteria because that will end up bringing people who really want to be here. We ended up moving people. The vast majority of people who joined Gameto in the beginning are people who moved to the state of New York, the city of New York to work for Gameto in person. 

People from all over the United States and abroad who said that this is a match for them. Finding your job is a matchmaking exercise, right? The job needs to be good, and you need to be good for the job. If you’re good at it, you’re going to love it. And then you initiate that cascade of the positive multiplier effect.

We ended up with people who are committed. They moved in with their partners, they moved houses. They wanted to be here. And for that reason, they were even more excited to give all in because you’re going to push a bit harder since you’ve moved, right? You don’t want to decide after two weeks out, we’re not going to do it because we’re not recruiting enough patients now that I’ve moved to New York to do this. 

That turned out to be very positive. Even though initially, there were concerns from others. We definitely try to hire different people that compliment each other. Knowing what your strengths and weaknesses are and knowing how to map them and trying to find different people.

One of my investors, Kristina Simmons from Overwater Ventures, when I started going for, more feedback and training, like how do you pick the right people? One of the questions that she did tell me was, you should ask them what is the most difficult challenge you had to overcome?

She [Kristina] had worked with Khosla Ventures, and in Andreessen Horowitz, in Lululemon, hired a lot for her portfolio companies to harvest her own funds. That was one of the best questions that I started asking in every interview. I’ve decided to acknowledge my background, a medical doctor. As doctors, we are detectives. We study people.

From the moment a person comes in, you start observing their behavior. What they say, how they look, and you try to picture them. You try to predict what type of a person they are to make your diagnosis. Sir Arthur Conan Doyle, the author of the Sherlock Holmes series was in the end the physician. I try to embrace even the things that I used to do when it comes to psychiatric assessments on my placements around trying to analyze people.

 One of the two key things that I try and do when I do the interview process is how do you react to stressful situations and how resilient you are under pressure. What’s that most difficult challenge you had to overcome? I try to picture it. You were in those situations. In addition to all the skills match, I think that resilience, that pressure is one of the most important factors of working successfully in a startup. Because a startup, especially in biotech, especially in this climate, is essentially in an adverse environment. You need to be somebody who thrives in that adverse environment and gets excited by the difficulty rather than put off.

It’s not for everybody. I certainly don’t recommend this to everyone, especially during the early stages. But I think with that group of people who compliment each other, have good communications, who are highly resilient, very motivated, and have already put a lot… it’s personal, they made them move to be here to do this. They’re excited about the mission. We managed to really gather a group of excited people. That helped us deliver in that phase. Now, obviously different methods for different phases, but that was one positive.

The mission that you mention certainly helped. Because it is a unique mission. There’s not so much funding in terms of biotech for women’s health. It is a neglected area. It’s not difficult to really get excited about this. Those are some of the things, that, helped us select the first few people who really built the company up until now.

Simon Burns: When people talk about founder-led biotech companies, they talk about this new movement of not started at, at a Cambridge studio, not professional CEO hired to run a company, but rather personality driven, mission-centric, Silicon Valley-type companies. I can’t think of a better case than you. You seem to have kind of a reality distortion field around the company, incredibly mission oriented. You really built a very distinct company culture. Is this the starter of a lot of companies you think that’ll look like Gameto? And how do you think of founder-led biotech now and into the future? 

Dr. Dina Radenkovic: Gameto was a very unique example that we started with the sponsor research agreement. Through that sponsor research agreement, we had the ability that before raising a Series A, we had a lot of the basing underlying science done. We were able to license retrospectively some of the work that was doing adapted for Gameto’s first product idea that we came up with.

The sponsor research agreement was definitely helpful. And it’s a hybrid where a lot of foundational research could be de-risked. It’s an efficient way to look at the biotech businesses. I do believe that with [00:15:00] founder-led biotech, there is that component of just love, love for your product. If you break down love down the Medicare terminology, you’re in very high neurotransmitters. It’s like giving a people general anesthetic in order to operate on them.

When you really love and you’re passionate about a mission driven company, you’re going to go through hardship and just do more. Even if it’s harder, there’s nothing they can do to you because you’re happy and you’re in love. You’re numb. You basically have strong neurotransmitters that are acting for you to be resilient during that process.

 It’s very strong, it’s powerful, it is captivating, it is charismatic, it brings people along and it gives you more energy to power through. On the other hand, the disadvantage of founder-led biotech can also be because of that love, emotions can cloud your judgment just like in any other, scenario. An important trap there is that, in the end, you cannot mix that with your personal identity.

You cannot mix that with, “oh, I really love this, this is the impact we want to choose,” but actually economically it’s a different decision that is best for the impact, for the company, for the return of the company shareholders. It I think that is important you get that love and personal touch in order to drive things forward, but also remain in control. Don’t let the passion and your inner involvement cloud your judgment and prevent you from making rational decisions for the business.

That can even be realizing who you need to bring along above you or step down or change roles. In terms of biotech, the problem is it’s so expensive to build something from start to finish. I do believe that we are beyond that model where you can just like, hire an executive who has done 50 of these jobs and he or she doesn’t really care that much about that.

They could very easily be defeated by somebody who was more mission driven, who cares more about the topic. However, I still feel the right balance would be something, like, founder-led biotech in more biotech incubators where you could create certain, places, collaborations with, the know-how, things on manufacturing the regulatory. A hybrid of something like that would be the best stage forward.

Hopefully, other advances in this space are going to enable that it becomes less capital heavy. But it’s because of this regulatory component some of our hybrid will probably win.

Simon Burns: At Vial, we think a lot about exactly that. How to reduce the capital costs to run clinical trials. How to do that technology. But there’s lots of other enabling technologies making it easier to start biotech companies: virtual labs, all sorts of other things. Is there something you’re tracking closely that you think will come through and enable a whole new generation of biotech companies to be started?

Dr. Dina Radenkovic: At Gameto, we built our largest omics library of reproductive cell types. That’s going to enable us to build that platform. We sequence. That’s going to enable us to do better in the future. We use software like Benchling where we recorded from all of our trial sites. We had the same results coming in from Peru, United States and Spain when we’re doing the first phase of our pre-clinical studies.

We are excited to partner with companies like, Vial to work on digitally- oriented clinical trials, patient recruitment and patient engagement. Often, why clinical trials end up getting negative results is because they don’t end up reaching the clinical significance in their large population because reproductive care is one of the easiest to drop out. You got into a trial and you’re just going to baby. Your life is falling apart!

It’s a huge event. You don’t care about the trial at that given point. So What we see is this large dropout on follow-up, and the speed of recruitment. In reproduction we are focused around people who are still relatively young. They all use their iPhone. Reproduction is still for the first half of our lives, often.

With technology we can recruit people with more targeted recruitment and we can engage them. We can focus on engagement. So there’s no loss of follow-up. If you look at the numbers there, you could reduce the cost of a clinical trial by 30%, 40%. That is also something I’m excited about. Those are things that are potentially already available that are cutting. In the future, I’m already seeing labs that are with liquid handling robots, a lot of robotics working 24/7 in the labs We built the Deovo program. The first ovaried, stem cell derived, female reproductive system. Recently, the FDA has passed, I’m sure you’re aware, that animal research may not be necessary. Which, essentially, means that we’re going to, in the future, see a lot more organoid work and organs on a chip for the early phases of drug discovery. We can have a liquid handling and other robots in our lab testing this 24/7.

That is super exciting. We work seven days a week. Because we work with clinics and hospitals. I’m a physician, so for me any day is a working day. It is incredibly exciting. That can lead to a lot more efficiencies, faster development. Another thing that is also super exciting is obviously AI. Everybody’s talking about ChatGPT and what could it do. But, what could it do for healthcare in the next 12 months? How will we be inventing? 

Historically, AI has not done that much for drug development. I don’t know what your thoughts are, but my personal opinion is that we haven’t yet seen that [laughing] huge impact. Because we haven’t doesn’t mean that we won’t. Will we need, biotech CEOs? [laughing] What’s going to happen? How quickly is that going to come up with novel companies? That is really exciting. It’s difficult to predict how drug development is going to work in 10 years. Seeing that right now, I hope it will be a lot better. I’m absolutely positive around the use of technology to program biology.

We’re already there with all of the cell engineering. There’ll be more tools to get this up and going. And it’s really important for the United States to stay on [00:20:00] top of that. I believe that who stays the leader in life sciences is going to be hugely geopolitically important, globally. 

Simon Burns: Well, with that, Dr. Dina, it’s a total thrill, chatting with you today andt o partner with Gameto. Thanks so much for the time.

Dr. Dina Radenkovic: Thank you so much.

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