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Steve Uden: Co-Founder and CEO of Rallybio · BioBoss

• 0:00
  John Simboli: Today I'm speaking with Steve Uden, CEO of Rallybio, headquartered in New Haven. Welcome to BioBoss.
• 0:07
  John Simboli: Steve.
• 0:09
  Steve Uden: Thanks, John. It's great to join you. I'm really looking forward to the conversation.
• 0:12
  John Simboli: Steve, what led to your role as co-founder and CEO at Rallybio?
• 0:17
  Steve Uden: Like so many things in life, it's a mixture of the poetic and the prosaic, really.
• 0:19
  Steve Uden: On the prosaic side, I was working with Martin Mackay, the other co-founder and Jeff fryer at Alexion, and Alexion went through some big changes. So we realized it was you know, we were, time to go and do something different. So that's the sort of the prosaic. You know, so often in life circumstances sort of move you in a particular direction. The other side of that coin is I've sort of made a point in my career, in my life, quite frankly, of always taking on a new challenge, I've had the good fortune to work right across the entire spectrum of the R&D space for everything from sort of discovery research all the way through to setting up Medical Affairs, I've worked all around the world. As you know, I've worked in Japan, I've worked in the United States. So to some extent, this was the next big challenge, create your own company and build it in your own vision. But I think everybody in the company, actually, because many of us were from Alexion, had been bitten by this idea of treating rare disease. So you know, a bunch of things all came together, you know, circumstances that were making me think where to go next, a desire to try a new challenge every time and then there's sort of interest and passion around rare disease and the opportunity to make huge differences for patients for whom there are no therapies at the moment. All sort of linking back to my origins as a physician, and going to medical school, because I wanted to sort of improve people's health.
• 1:40
  John Simboli: What were you hoping to achieve at Rallybio that you might not have been able to do, really, anyplace else, just because of the factors of what you were looking to create?
• 1:48
  Steve Uden: I mean, fundamentally, you know, you're creating your own company from the ground up. And it's sort of an opportunity to sort of bring all of that together, the best of drug development, the best, you know, the best therapies for patients, the best group of people, create the right culture, and do it, you know, from the ground up. And so that was really what the attraction was, to be able to apply all of this experience that I have, and Martin and the other colleagues who joined us to really sort of then create a company that was going to be passionate about great science, great drugs, doing things the right way.
• 2:23
  John Simboli: Did you and Martin and Jeff, at any point, say, we have an idea for a really interesting approach, perhaps we'll find an existing pharma company that will allow us to build this within? Or did you know, from the beginning, it had to be built from scratch?
• 2:36
  Steve Uden: The issue is always the culture of the place you're going to go and the sort of political dynamics, I think the idea that, you know, you could go in and change anything that's. . . and to create what we've created here is, would just never happen. But I've never been naive enough to go in and think you can change, you know, 50-60 years of what's gone before.
• 3:00
  John Simboli: When I talk with people about the work we do in biopharma, what people often jump to is Big Pharma, and selling a product, as opposed to the idea of developing an idea and the science that leads to that. So in one, they kind of picture someone in office and in another one, it may be hard to picture exactly what a CEO does, and it may be hard (of a biopharma company), it may be hard to explain to others, "What do you do all day?"
• 3:29
  Steve Uden: I think if I'm explaining to somebody for the first time, as you say, the first thing is you got to really go right back and talk about what is different between biopharma and pharmaceuticals. I think, you know, most people have a vague idea of Pfizer or Bristol Myers Squibb. But even though they think of them usually as sort of large marketing organizations and you often have to go right back and say, Look, you know, the drugs come from somewhere. And despite what the press would have you believe, that the vast majority of drugs are invented in companies. But they're not all invented in big companies. Very often, it's small groups of people, like Rallybio, who take great ideas from other scientists and put them together into a plan and a package that people find interesting enough that they'll invest in you. So you know, what do I do all day long? I work with our team of people. If we're not thinking about the science and the minute-by-minute stuff to move the program forward, we're thinking about how can we raise money to keep doing that? What is the right company strategy?
• 4:28
  Steve Uden: How do we sort of work well with our stakeholders, that's obviously the board, obviously investors or potential investors, obviously, the scientists and the academics who are interested in our space.
• 4:41
  Steve Uden: Then we've got all of our partners who help us get the work done. I mean, you know, these clinical trials, employ armies of people to actually make them happen. We don't employ them in Rallybio, we use third parties, so you know, you're working with those. So a lot of my job is really just sort of stakeholder interactions, thinking about the company's strategy, making sure that the teams have got everything they need to get the job done. We're really lucky, you know, we've got a very mature group of people. So very rarely, if ever, am I having to deal with sort of human interactions, Fred doesn't get on with Mary. But, you know, we've been very careful about who we chose. And we're very privileged in leading a very experienced team. Many of us have worked together in the past. But it's all around, you know, finding a way to take great science, turn it into a drug that could potentially change the world.
• 5:29
  John Simboli: What have you found about your management approach or your way that you deal with people that works for you?
• 5:34
  Steve Uden: I think number one is being very clear about what it is that we set out to achieve. I think that this sort of concept of how, you know, selection and maintenance of the aim, as they say, in the military, what is it you're actually trying to achieve, and let's get everybody, make that really, really clear. I think that's the most important thing that one can do as a leader, which is set the goal, set the vision, set the direction of where you want to go, then everyone's aligned. The second thing is, I think it's important that you actually know your people. I mean, genuinely know them, you know, what sort of people are they? How do they like to work? Are they, you know, extroverted? Not through sort of Myers Briggs, just by sort of human interaction. What about their families? You know, what do they do when they're not at work? What what is it that sort of makes them tick, I think is also important. I prefer to work by setting goals, and then sort of leaving people to get on with the job in the way that they think is best. I trust people but then make sure that I do check in with them on a regular basis. One of the habits I've got into over the years is I tend to meet with everybody who reports to me directly one on one. But I do think it's good to check in, partly, to really understand the work that they're doing, partly to reassure them, that you respect them, and want to work with them. And just to make sure that, you know, there aren't course corrections needed, or, you know, people are over-engineering something or missing the point. So, close interaction with the team is important, I think. So those are the fundamentals for me.
• 7:01
  John Simboli: As you recall, as a young person, eight, nine, ten, whatever the age may be, your interests, how you thought your life might go, and perhaps what you perceived your parents thought was in your future. What did you see, as you recall it, and how does it connect, if at all, to your professional life?
• 7:17
  Steve Uden: Even by that age, looking back, it was beginning to become clear where my career would go. So I'd already got sort of an interest in science, you know, as best as one can have as an eight year old, but I still love when we did, like, you know, general science.
• 7:30
  Steve Uden: Secondly, I wasn't I wasn't a weakly child, I had a couple of sort of health issues, minor health issues that required me to go into hospital and maybe go to the doctor a bit more often than your average sort of eight, nine, ten year olds, so sort of medicine began to intrigue me just working with, with other physicians. And then my father was relatively older, he was of the war generation. So he'd been an officer and sort of risen up through the ranks. So about that age, he was the founding headmaster, school principal, of a brand new school in London, where I was growing up. So I sort of saw him as, he was a leader, a great leader, a great manager. So you know, those those three factors all coming together–an interest in science, even at that young age, I'd interacted with the healthcare system and found it really kind of inspirational in a kind of a way and then having a father who, you know, was clearly a leader in his own right, and fascinated by what he'd done during his life. And here we are, you know, 50-60 years later, and it's all sort of come together.
• 8:35
  John Simboli: When people say, Steve, who is Rallybio, how do you like to answer that?
• 8:40
  Steve Uden: I like to answer by saying that we are a biopharma company, our mission is to take devastating diseases and devastate them. We are passionate about working on therapeutics that in one way or another, will transform people's lives. We're what's known as a portfolio company, we're built around the team of people rather than the platform technology.
• 9:01
  Steve Uden: And you're probably aware, there are sort of two flavors of biotech, there's the platform, gene therapy, antibodies, what have you. And then there's the portfolio where you build a strong team and then bring ideas in. So that's our business model. There's about 25 of us, all of whom have had an amazing track record. And with that strong group of people, we were able to attract the financing and then bring in the programs on which we're working. So we're a portfolio company, we're focused on rare disease, our mantra is devastating diseases and devastate them. And that can be anything from, if you like, our lead program where the vision is to eliminate a disease, or a preventative approach, all the way through to our programs in complement where we are wanting to have a therapeutic that will not be at all burdensome for patients, and enable us to apply that sort of pharmacology to a vast range of diseases which currently, where we know complement almost certainly has a role but currently, there's no drugs.
• 9:56
  John Simboli: In the time that I've known you, I've known the work that you've done in terms of rare disease and complement and many other things as well.
• 10:01
  John Simboli: But I want to ask you about the rare disease part of it. When I first worked for a company that was focused on rare disease, working with Alexion, it was so different than anything I've ever experienced because of the proximity of the science team to the people that they were helping. I can't think of a better way to say it than proximity. But at what point in your training and your work experience did you first encounter the rare disease component? And and how did it affect you?
• 10:30
  Steve Uden: Probably my first foray into rare disease in its broadest sense, was just prior to working at Alexion, when I was working at Novartis Oncology, and I was there at the time that, you know, this sort of patient-specific therapy was now really beginning to take off, that you're not just sort of blasting patients with chemotherapy, but you're finding the subtle mutation and trying to, alter how small subgroup of patients interact. But it was probably, in a more traditional sense, which is the sort of non-oncological, it was my time at Alexion. And, as you say, you can see the impact much more clearly. One of the the interesting things is, of course, that, typically, your understanding of the disease itself is much greater, because, typically, rare diseases are due to discrete genetic differences.
• 11:23
  Steve Uden: And if you can fix that, you can then trace back from that genetic component, you can trace all the way back through to describe and understand the pathology etc. Whereas when you're dealing with these more sort of public health type problems, diabetes, what have you, it is multifactorial, and what might have made you diabetic could be very different from me and from the guy down the street. So it started at Novartis Oncology, seeing the way that understanding genetics could really sort of help simplify, if you like, the the pharmacological approach, then at Alexion, on how to take it to the next degree. You can get to clear go/no, go pretty quickly.
• 12:03
  Steve Uden: Now, having said that, with our lead program, it's a different approach to prevention. So that's quite a monster. But we once we get into patients, I think we're going to know pretty quickly whether or not the drug works. The issue, of course, is bearing in mind that we're going to be treating pregnant mothers.
• 12:18
  Steve Uden: The journey there is not as quick, simply because there's no room for error. Not that there's any room for error when you're developing a drug, but with a healthy mum, there's zero.
• 12:30
  John Simboli: Steve, can tell me something about Rallybio's lead drug candidates and why, what the need is?
• 12:36
  Steve Uden: Our lead program is an approach to prevent something called fetal and neonatal alloimmune thrombocytopenia, FNAIT. Now, what FNAIT is, it's due to a genetic mismatch between a protein on the surface of the mother's platelet and a protein on the surface of her fetal platelet. There's an antigen called human platelet antigen, while we all have it on our platelets, in a small number of people there's a single amino acid change. The protein still works, but there's a shape change, hence it's immunologically active. So if the mom has this rare mutation, if at any time, but the baby's platelets get into a circulation, bleeds from the baby into the mom are quite frequent during pregnancy, and certainly at delivery. And if at any time that happens, the mother's immune system will recognize these platelets as foreign. They've got the normal protein, she's got this slightly abnormal protein, her platelets here will make antibodies against this protein. Antibodies readily cross the placenta so now they're these antibodies flood into the baby and destroy the platelets. The antibody now finds the platelets inside the fetus, but the level of the antibodies can be so high that the destruction of the platelets overwhelms the ability of the little fetal bone marrow to replace the platelets. Now, although the baby is all wrapped up inside the mother's womb, if there's no platelets, the smallest bleed will just bleed and bleed and bleed. So hence you get intracranial hemorrhage.
• 14:09
  Steve Uden: It's the most common cause of intracranial hemorrhage. It can cause miscarriage, major problems with delivery, etc. And of course, because it's an immunological phenomenon, once the mum's mounted these antibodies, all future pregnancies will be at risk, not just that pregnancy, but the next one and the one after that.
• 14:26
  Steve Uden: Our approach is going to be to prevent this. In other words, identify the mums where this mismatch occurs, and treat them during pregnancy to inhibit them having this immune response.
• 14:37
  Steve Uden: Now, the good news is that there's a much more prevalent red blood cell mismatch. That's something called Rhesus disease of the newborn. Now many people have never heard of this. Now when I was a medical student this was the big breakthrough that had occurred in the decade before I went to medical school.
• 14:57
  Steve Uden: If you think about your blood group, this positive-negative thing is due to something called Rhesus. Now Rhesus negativity is very common, 17% of the world.
• 15:09
  Steve Uden: So this mismatch between red blood cells was quite prevalent back in the day. Now instead of causing no platelets, it would destroy the red blood cells, so the baby would be catastrophically anemic inside the mother and go into heart failure. Now, the interesting thing is that we speak to people, even people of our generation, John, they've never heard of this syndrome. It was the scourge of obstetrics up until the 50s and 60s, and the treatment approach is exactly the same as we're doing. In other words, check the mum for risk when she first turns up, if she's at risk, give a small dose of an antibody during pregnancy and delivery to prevent the immune reaction and get rid of the disease. Now, the difference is that this mutation on platelet is much rarer than the Rhesus red blood cell platelet.
• 15:54
  Steve Uden: So, it's only recently that the biology was worked out. But our lead program, so to get right the way back, in our lead program is to identify mums at risk of causing this catastrophic loss of platelets in their fetus, Identify early during pregnancy, treat the mum during the pregnancy with an incredibly small dose of an antibody—a naturally occurring antibody—prevent her from having an immune reaction. So the baby comes out healthy, she hasn't had an immune response. So the next pregnancy will be fine, et cetera. I can think of nothing more inspiring, quite frankly, than, if this works, to have a therapy that tackles a catastrophic rare disease, but it doesn't tackle it by treating it. It tackles it by just preventing it from ever happening. And my vision for the future is that 30 years from now, people will be on a podcast, and they'll be saying, well, there's this thing called FNAIT, which has completely disappeared. So I'll have to tell you what it is, because, you know, when I was a medical student, this was the terrible thing. And now all due to this company Rallybio, it's disappeared. So that's what it is, an approach to prevent a rare disease, that if don't prevent it, can end up with a child that grows into an adult with lifelong disability. Back to your earlier point around you're much more intimate with the patients in rare disease than other diseases, there's a mother who lives on Long Island, who has visited the company who had a child with FNAIT. We've met the patient support group, this is a mum, who's had a grandmother who had a family with this syndrome. So, you get to know these people and just hear the stories. It's really quite awful. So that's our lead program. If it works, we will actually eradicate this disease.
• 17:47
  Steve Uden: Can't wait.
• 17:49
  John Simboli: How do your choices about the pipeline express your vision for the company?
• 17:52
  Steve Uden: Two things drove the pipeline. Number one is would the therapy have a transformative effect, the potential for a totally transformative effect in a rare disease? And secondly, is the science that underpins the idea strong? We've looked at when looked at, it must be 1000s of potential opportunities. And they often failed most, usually, most typically, because the science was pretty weak, one way or another. So with our lead program, we found it in a very small, what I would call academic startup. It was in a company based of all places in Tromso in Norway. The mutation that causes this platelet problem is, the further north you go, the more prevalent. So there is nowhere further north than Tromso. So that's probably why. But great academics, they worked out the fundamental biology, they've worked out the approach, how you could prevent it, but they didn't know how to move a drug forward and do the testing to be confident, as one can be, that you can treat mothers. That's where we stepped in, we brought our expertise to bear to say right, take it to the next step, because then we can work out how you can do the safety testing and create animal models, how we can work with investigators to be confident that we can take this into mothers, etc. If I look at the complement assets, great drugs, I mean, if this drug works, it will mean the patient can treat themselves with a small injection, like giving themselves an insulin shot once a week. Low cost of goods. So you know, you could explore the entire gamut of rare disease.
• 19:28
  Steve Uden: The problem had been that the drug was produced in E. coli, like a lot of biologics, but there'd been some sort of problem with the manufacturing that was causing major side effects. But everybody thought it was the drug itself. It wasn't. it turned out it impurities that were leaking from the manufacturing process into the drug product. And we were able to work with the company that had the original technology to fix that. You know, our approach in hypophosphatasia. We looked at some some work that had been done in what's called a double knockout mouse and we realized that maybe you could treat this with a pill once a day.
• 20:03
  John Simboli: When people hear the Rallybio story, what do they get right? What do they get wrong? How do you help them get onto the track that as you see the company?
• 20:11
  Steve Uden: I think early in the days of the Rallybio story, this whole concept of this FNAIT was very difficult for people to get their heads around—prevention.
• 20:19
  Steve Uden: What you're going to treat pregnant mothers with? Like many rare diseases, no one had ever heard of it. Now, through a lot of hard work, we've educated vast numbers of stakeholders in what is FNAIT. And so, increasingly, people come to us knowing what we're trying to do.
• 20:39
  Steve Uden: The next bit of the story that's tough to tell is that these are pregnant mums, we've got to be very step-wise. We're having to be, for obvious reasons, very methodical, I think most of them pretty quickly get to understand that this is a really experienced team of people. One of my colleagues, Amanda, our Head of Business Development, she was at Bio, the big partnering meeting. And she was talking about our portfolio to many companies, who might want to partner with us, and feedback from big players, big, credible pharma companies, and gosh, the science that comes out of your team is the best we've ever seen. That's one thing, they pretty quickly realized that this is a team of people who really knows what it's doing.
• 21:20
  Steve Uden: Early this year, J&J got into a collaboration with us. We're trying to prevent the mum ever having this immune response, their approach will be to find the mums who sadly had this immune response, and then try and damp down, in future pregnancies, the impact on the fetus. Totally synergistic approaches. I think, for me, the best bit of news was, look, you know, we're not the only people worrying about this, there's another big credible player out there. We're not in competition with them, we are working together in a collaboration to cover the whole waterfront. In complement, there's a lot of people's playing in the space.
• 21:56
  Steve Uden: Explaining why we're going to do something very, very different.
• 21:59
  Steve Uden: The good bit is they very quickly get the science we're doing is first class and the team really knows what he's doing.
• 22:07
  John Simboli: The word partner can have many different meanings for a biopharma company like Rallybio, but let me just ask, broadly, who is a good partner for Ralybio?
• 22:16
  Steve Uden: If I'm thinking about investigators, and people are working with us on our clinical trials, these are obstetricians who are passionate about making a big difference in their practice. And then amongst those, obviously, some people have really given their life to FNAIT. I was on a call with an obstetrician a few weeks ago, who said, I've divided my career into three epochs, or decades, I'm in the final epoch. And what I want to do is work with you guys to eliminate FNAIT, it has been the scourge of my practice.
• 22:47
  Steve Uden: So people who are really keen to get involved in research. If I think about investors, it's got to be people who really understand FNAIT and are prepared to be in for the long game. And then we've got all of our partners, because to get the work done, we need a lot of you know, CROs and CMOS. So again, we take great care to select people both their scientific prowess and the quality of the work that they do. So it sort of depends on the stakeholder, but fundamentally good science and good quality underpinning everything they want to do, we'll get on with it very, very well.
• 23:24
  John Simboli: Steve can you bring me up to date on where the progress is with your lead asset and what you anticipate in the coming weeks or months?
• 23:33
  Steve Uden: I think we've done everything, we need to get ready to start phase two, whether that's talking to regulators to agree on the package of data that would satisfy them. We are now getting ready to start the phase two study. We're going to start screening mothers for our phase two. Now, screening is the key word because earlier on, we talked about prevention. So if you're in prevention, what you'll need to be doing is testing. It will become standard practice as it is today. You know, when a mum goes to the doctor, the first time and says I'm pregnant, the doctor runs a series of blood tests. Is she diabetic, is she Rhesus negative, what's her blood group, etc. So the first thing will be to screen all of the mums going to the doctor to see whether they have this mutation, and whether they are at risk of causing this problem in the baby. Now, the goal is by the end of this year, all of the centers that are going to be involved in the studyhave started to screen mums to find a mum who may have this mutation, who we could then treat to try and prevent her from having this immune response. I think it's going to de-risk three big things for us. Number one is the regulatory risk. So that's the first bit of de-risking. And the next bit of de-risking, of course, will be, will mothers take part in a clinical trial?
• 24:45
  Steve Uden: We spent a lot of time talking to investigators and doctors who look after patients and it's been a consistent feedback that once a mom knows that the baby is at risk, they will do whatever it takes, but we need to de risk that. And then the third thing, how does pregnancy impact the pharmacokinetics. We all know that over the nine months of pregnancy, the mom's blood volume goes up by 40%, her metabolism changes, etc.. So will the dose that worked well in the phase 1 proof of concept studies provide adequate drug level when the blood volume has gone up 40% Or will you have to adjust the dose for the mom during the pregnancy or, if at all, et
• 25:26
  John Simboli: How did Rallybio choose to start off in New Haven?
• 25:31
  Steve Uden: Many of us were at Alexion. And many of the people at Alexion had worked in one or other of the big pharma companies that had in their heyday, major research facilities in and around southern Connecticut. Pfizer up in Groton, Bayer, in West Haven, BMS at Wallingford, and of course, still Boehringer-Ingleheim. Now, the good news is two things, there is a sort of nascent biotechnology hub here. There is a commitment to try and make Connecticut a place for biotech.
• 26:02
  Steve Uden: There's a huge pool of talent, there's a huge number of people here who are very experienced and know the space well. So it was sort of we were here, it's a great place to be, the state is trying to support us. And there's just so much talent that we could tap into who was passionate about rare disease.
• 26:20
  Steve Uden: There is a benefit, I think, in being able to just walk across the green to a lab in Yale or up to Science Park.
• 26:30
  John Simboli: What areas of thought leadership regarding the future of biopharma are currently the most engaging for you personally?
• 26:37
  Steve Uden: I think there are two actually, they're almost at the sort of opposite ends of the spectrum. The first is how will artificial intelligence change what we do? And how can it be best employed? There are some obvious possibilities around helping out with a drug discovery process. In fact, use of computer models, and computational chemistry has actually been around for quite a long time, particularly in Connecticut. But will the impact be as revolutionary as people predict? Or will it be incremental? Or, would it not make a huge difference? And we've been through a number of these big, this is going to change the face of our work, whether it was high throughput screening, or now we've got the human genome and what has tended to happen is they're all incremental, rather than revolutionary. And in fact, one of our projects, this pill to treat hypophosphatasia, is in collaboration with a company that has for about the last five or six years been using artificial intelligence to them in medicinal chemistry. So that's one end, AI, is how much of a there is there there? The other end actually is sustaining our industry. How are we going to train, develop, educate the next group of biopharma leaders and innovators? I didn't know it at the time, but I had the huge good fortune and luck to start my career at Pfizer. I mean, not only was it, and it still is, a great company, but it was just such a great place to learn the ropes of drug development and how the industry works and interact with colleagues from all different fields. If you go straight from academia into a small company, you're never going to get that experience.
• 28:21
  Steve Uden: And how do we prepare the next generation of leaders? And I think people sort of despai, well, you know, you can't do it working hybridly. I sort of approach it differently. Our challenge is to make it work, bearing in mind that the future of work could well be hybrid. So we're not always going to be able to sort of stand by the water cooler or sit somebody on your knee and sort of teach them from the master. So the question is, how can we do that? But I do worry about that, because it's such a great industry, great work that we do. How are we going to make sure the next generation is best prepared to do that?
• 28:57
  John Simboli: Steve, thanks for speaking with me today.
• 28:59
  Steve Uden: Quite searching questions, John. It's quite nice to sit back and actually reflect on how one got here in the first place. I hope some people find it interesting. I've certainly really enjoyed talking to you.