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Iain Kilty: CEO of Sitryx · BioBoss

• 0:00
  John Simboli: Today I'm speaking with Iain Kilty, CEO of Sitryx therapeutics, headquartered in Oxford, UK. Welcome to BioBoss, Iain.
• 0:09
  Iain Kilty: Thanks, John. I'm looking forward to the conversation.
• 0:12
  John Simboli: Iain, what led to your role as CEO at Sitryx?
• 0:15
  Iain Kilty: So I took on the role relatively recently, actually just a couple of months ago, but I've been working with Sitryx for just over the last three years. I was the CSO before transitioning into the CEO role, and it was a great opportunity for me to lead a company that I'm passionate about and really believe that we have a chance to have a huge impact on patients who suffer from autoimmune diseases. And that's really been the area I've spent my whole career in different guises. So prior to Sitryx, I was working in Cambridge Mass actually, with Atlas venture, as a CSO for one of their immunology companies, but also as an entrepreneur in residence, helping them seed new companies in that space. But spent the bulk of my career actually at Pfizer. I was at Pfizer over 20 years, both US and UK, always in the immunology space, but a variety of roles, from leading early target discovery teams through to leading clinical clusters in rheumatology and dermatology, before ultimately being responsible for their preclinical portfolio in INI.
• 1:17
  Iain Kilty: And as part of that role, actually, I was doing a lot of work, working with biotech, and whilst, I guess lots of fantastic things about Big Pharma and Pfizer and had an amazing time there, learnt a huge amount, had the opportunity to contribute to marketed therapies now, but the dynamism, the opportunity to impact things, to really drive programs at speed and take risks was was more available to me in the biotech world, and I've really enjoyed making that transition.
• 1:48
  John Simboli: What's it like to be a CSO and then become a CEO?
• 1:51
  John Simboli: What sorts of understandings do you have now? I know you're in the job relatively a short time, but what's it like to be a CSO versus what's like to be CEO?
• 2:01
  Iain Kilty: Yeah, so it's, as you say, relatively early in my CEO experience, but the previous CEO actually is chap called Neil Weir. He was the CEO from the start of Sitryx, and when the company was founded, and he's still within the company, he's now president of the company.
• 2:14
  Iain Kilty: Which is great for me, because Neil's been a mentor all the way for me since I joined Sitryx, and this was part of a succession planning it was even discussed as I very first joined as the CSO. And obviously, as a CSO, you're primarily focused on driving that scientific portfolio. And I joined at a time the company was really evolving from having some early targets to driving those targets towards development candidates and needing to become more of a professional drug discovery or drug development organization, which was a huge amount of fun, and we've now been able to deliver multiple programs through those stage gates. So with respect to the transition of role over this time, Neil's given me opportunities to be heavily involved in the investor discussions, the pitches, the strategic thinking of the company and so on. So it's less of an abrupt you're the scientist. Oh, now I want you to be involved in all of these other things than a transition over time, which has been great because, obviously I know the company very well. It's not like coming in as a CEO and trying and learning the science, learning the strategy and so on.
• 3:20
  Iain Kilty: I've been involved in building the company to this point, and that was one of the reasons this was a really exciting opportunity for me. Because I said earlier, I think I have great belief that we have a chance to really make a difference for patients in what we're doing. I really like the team, and I think we have some really quite exciting assets to take forward to the clinic now.
• 3:42
  Iain Kilty: The key thing even in these early days, is my focus is moving away from that management of that scientific portfolio on a day to day basis to all the other pieces, thinking about the discussions with the bankers, the discussions with lawyers working with the board, and that's an interesting reporting relationship that's new for me, I've always had a direct boss, and whilst I report into the chair of the board, Pierre Legault, and he's been also a great mentor for me, you have lots of other players on the board as well who are from different institutions, different organizations that you're working with. So huge amounts for me to learn on that front, lots of connections, lots of talking to people and a lso important for me within the Sitryx organization, that it's not just the science part of the organization that feels they know Iain. Now we're small enough for 45 people that I knew everyone anyway, but it's a different relationship now to make sure I'm interacting with the finance team and in a different way, the operations team and so on and so forth. So yeah, lost lots to learn, but it's a transition more than any sort of revolution in the way I'm doing things
• 4:49
  John Simboli: From early on in your in your career, your 25 years with Pfizer, did you picture at some point being a CEO? Or is this something that sort of evolves as time goes along?
• 5:00
  Iain Kilty: Yeah, so when I was at Pfizer, I don't think I necessarily pictured myself as being a CEO. I think actually, as I developed in my career at Pfizer, I would take on new levels of responsibility and always enjoy it, and once you got comfortable with that, you'd look at the next role and think, well, I could have more impact in that next role. And then look for those opportunities to build out my toolkit, build out my experiences to be in a position to take on those next roles. And as I mentioned earlier, actually I spent a bit of time in the clinical phase of drug discovery while I was at Pfizer, which was not my initial background. I was PhD scientist, very much lab based early on in my career, but really research focused. But that experience for those few years was hugely impactful in how I then did my job leading a portfolio through to development, candidate, nomination and early, early development, So phase one, 1b type work. So in a similar guise as I talked about, I was interacting quite a bit with biotech companies when I was at Pfizer, and that's what really fired my interest, that a dynamic place to work. I could really try and influence things.
• 6:06
  Iain Kilty: I felt I could bring experience from big pharma into that biotech setting and add value.
• 6:12
  Iain Kilty: And to me, that's one of the most important things. Am I able to add value here and really progress towards making drugs?
• 6:19
  Iain Kilty: Because fundamentally, that's what I want to do. I want to make drugs that change people's lives. And there's no feeling quite like being involved in a program that you get the first clinical data and you see it's working, and you think I was involved in that. That was an idea that we had on a PowerPoint slide and so on. So that drove my transition into a biotech and CSO was the obvious area for even my scientific background.
• 6:41
  Iain Kilty: But in a similar guise, my first CEO, I worked with a lady called Sam Truex at Quench Bio, who's a good friend, and again, another great mentor. I've been really lucky with the people I've interacted and worked with through the years. And there were lots of elements of what Sam was doing that she gave me the opportunity to learn about.
• 6:58
  Iain Kilty: And I thought, well, there's areas here that I think I could really help too, because I bring a different style, I bring a different way of thinking. And even then, I wouldn't say I was 100% sure that my next goal is to be CEO, but I certainly felt there were areas where I thought I could bring value again as a CEO with a slightly different background. Sam's background was more business development than a core science and so on. So joining Sitryx was similar and coming in as CSO, not necessarily absolutely setting my heart on CEO at all, but, but it really felt like there was an opportunity here, given what I've already described through the transition with Neil moving into a role as president and so on for me to take that next step. And I really do enjoy the business side of biotech as well as the scientific side. And I think it's you bringing those two pieces together that give you the best opportunity to deliver those new drugs for patients. And another quick comment, some of the exposure that I've had on that business side has also come through my entrepreneur in residence role at Atlas, and I'm a venture partner with SV health investors right now in London, and those things, you start to see those elements of the job. And again, felt, well, I think there's value I can add. I've got experience pre clinically, and clinically, the company's moving to more of a clinical phase now, and it's the next step in development for me, and hopefully I will be able to add real value to Sitryx.
• 8:30
  John Simboli: I want to ask you about the leap of faith part of this. You were well prepared, as I've understood what you just told me, and it's quite logical in some ways, in most ways, to follow that path that you follow. On the other hand, there is, I would say, probably, for most people I've spoken with, there is a leap of faith about going from something that's very big, like Pfizer or BMS or wherever it might be, to something that's new and getting started. And I remember a conversation with two founders who, one co founder spoke to the other and said, I'm thinking about starting this company, would you like to join me? The other guy said yeah, and they were both really excited as they told me the story, and then they said, then we went home and told our wives. So that's the part of the question I want to ask you about when you come to grips with that, this is exciting, but this is an unknown. How does one negotiate that?
• 9:17
  Iain Kilty: Well, you're absolutely right, and you've been in the environment, in Big Pharma, but you've been reasonably successful. It's reasonably comfortable. You're well compensated, and you've also, you've got teams you really like, generally, I did anyway, that's the hardest piece, in many respects, was leaving some of the people.
• 9:34
  Iain Kilty: You're also leaving value on the table, because you have various options and all the rest of it.
• 9:37
  Iain Kilty: So it is an element of leap of faith. It was interesting. I didn't need to go back to my wife and sell this. She knew that I was really ready to go, probably before I did, in some respects, because she could see how energized I was when I was working with those biotech teams, through some of the work I was doing for Pfizer at the time, and how I'd come back and talk about it and the receptions I'd been. And chatting to those guys, and I obviously discussed, I think I could, I could have an impact, that I could, I could do something that's valuable. And she, she was very encouraging, actually, well, if you believe it, just go, you should do it, which was fantastic. It's fantastic to have that sort of support at home, because yeah there's definitely a nervousness, and it's really interesting because one of the things I was most nervous about, actually, was job security moving into a small company. I was the fourth employee at Quench Bio when I moved there, so it was a small company at the time. But I'm not sure that actually, now I've been in that world for a number of years, I don't think that's really the right thing to be concerned about, because the reality is that with any of these, with any of these investor ecosystems, if you do a good job within that ecosystem, there's always need for people with experience and drive to join other startup companies or establish biotechs.
• 10:50
  Iain Kilty: There's no shortage of roles.
• 10:54
  Iain Kilty: Now, your company name may change more than it would at a Pfizer and so on, but, but I just don't think actually there's that there's such a big difference in job security. It's just a different type of security, as long as you could deliver. And I guess then the other piece that you always have, and you have as you step, well, I have as you step, from a CSO into a CEO role, is there's always an element of, you know, can I, can I do this effectively? You know, there's always a bit of imposter syndrome. And mind you, those sort of things, you know that those things keep you sharp, keep you focused, make you work hard, so I think that's just all part of the process.
• 11:27
  John Simboli: So here's a related question about how people think of a CEO as compared to another C suite job.
• 11:35
  John Simboli: So I spoke with a person who was the Chief Business Officer at a biopharma company. And he told me that he was accustomed to going into the meetings with CEO and the other members of the team and posing options, you know, we could do this. We could do this. And then he said, when he became CEO, he just without even understanding that he was he was doing that, he was explaining to his team we could do this and this. And he said frequently, suddenly they would turn to him and surprise, he was surprised by this, and turn to him and say, yeah, but which one are we going to do? So there is a collaborative aspect, but there's also an expectation, right, that the CEO will be a final decider. So again, probably early in the cycle, maybe I should ask you this in six months, but do people look at you any differently as the CEO than they did as the CSO internally?
• 12:26
  Iain Kilty: I think so. I mean, my natural style is I do like to make decisions. And we've done various analyzes with our LT, you know, all the different Hogan type analyzes and things to look at our different styles and I'm probably the strongest decision maker style within the team. So that piece is quite natural for me, and I quite enjoy that, being able to make a decision and move on. I like to make a decision before we leave the room. But yeah, obviously I like to listen to the team and so on. Now, as a relatively early stage biotech just moving our first wholly owned program to the clinic now, a lot of what we're talking about is in my area of expertise, because it's the drug discovery piece. So I feel comfortable around that drug discovery development. It gets a bit more tricky if you're talking about decisions you need to make around a legal decision or a decision about some things we've been talking about recently, the lease and lab space we might want versus not, and some of those things. So yes. So I think as you move more out of your comfort zone, those sort of decisions get harder, don't they? Now what's great is I have a really good leadership team who I can rely on to advise me and to be involved in that debate around any of those sorts of decisions that need to be made. But yeah, no doubt there'll be challenges in the future in that way. I think actually, one of the things I've already seen is just people treat you differently once you're the CEO, because you're not quite a peer anymore. And some of those, you know, much of the team, it's many of the team were my peers previously. And whilst you don't, I don't personally feel any different.
• 14:01
  Iain Kilty: You do notice the style of people's interaction can be subtly different. And I think you just have to get used to that, that you know you're in a slightly different position.
• 14:11
  John Simboli: When you first came to Sitryx, do you recall what it was in particular about the science that grabbed hold you? I'm sure you looked at hundreds of other options and possibilities at that time coming from Atlas, you saw many different things, I'm certain.
• 14:22
  John Simboli: So my question is, do you recall what it was specifically about Sitryx that made you say, I really want to investigate this?
• 14:31
  Iain Kilty: Yeah so there's, there's a few elements to it, actually. So I had the privilege, again, working at Pfizer, to work on particularly jak kinase inhibitors, which have become drugs and other programs which have really had an impact on patients, which is great. The way that those approaches work is that they're suppressing elements of the immune system, and from there you can drive a certain level of disease remission, but we kind of got stuck with the amount of disease remission we can achieve in rheumatoid arthritis, in inflammatory bowel disease and other indications. So we need to start thinking slightly differently about how can we really move that needle to drive greater therapeutic benefit for patients and drive more patients, as I say, into true remission and sustained remission at that. So actually, when I was at Pfizer, we were looking at different areas we could invest in to do that. And one of the areas we felt really had that potential was immunometabolism. So we actually had a group there, when I was at Pfizer, focused in this space.
• 15:34
  Iain Kilty: It was a space I knew pretty well. And the fundamental thesis for immunometabolism is that by modulating the metabolic pathway cells are depending upon, you can modulate the phenotype of those cells. So you can move a cell from in effect, a pro inflammatory cell, to more of a regulatory or homeostatic sort of type cell, and that has the potential to really drive much greater efficacy for patients.
• 15:57
  Iain Kilty: So the disease area was interesting to me. I think the other elements were, it's a small molecule company. I've got a lot of experience in that space. And going back to the point I made about, do I think I can make a difference in that organization and really add benefit? And then, fundamentally, it's super important it's the right team.
• 16:17
  Iain Kilty: And when I met previous CEO, Neil, Neil Weir, and some of the other leadership team at the time, I really felt that this is a team that would be fun to work with, but know what they're doing and have a clear vision of where they want to go. And equally, we have a great investor base, and that's also incredibly important, as you know, in the biotech world, seasoned investors who really understand drug discovery and development and I had the opportunity to meet with a number of the investors as well before I took the role and and again, was really encouraged that they would be great people to work with. So it was a mixture of the science made sense to me, I already knew some elements of it, the team were great and the investor base was good.
• 17:02
  John Simboli: When you tell someone who's from outside the industry that you're the CEO of Sitryx therapeutics, what do you think they picture you doing all day, and what do you do all day when you try to explain to them, no, I do this.
• 17:15
  Iain Kilty: So usually, if I'm asked, what do I do for a living? I would say, well, I work in a company where we're trying to make new drugs to help people with autoimmune diseases, diseases like arthritis and inflammatory bowel disease, eczema and so on. And then people have usually got a reference point there that they know somebody who who struggles with one of those diseases. And then perhaps, if that piece is clear, and they say, oh no, I understand that. But, is it pharma biotech, then I would jump in and say, well, I built a lot of my experience and skill set working in Big Pharma, but now I work in biotech and enjoy working there because of the dynamic nature of that business.
• 17:52
  Iain Kilty: But it's an ecosystem. Big biotech needs Big Pharma. Big Pharma needs biotech, so we still work closely with pharma and spends a lot of time with those teams. And then to what do I specifically do there? Well, I'm a scientist at heart. I'm focused on developing drugs that'll change people's lives, and perhaps tell them a bit about our lead programs in eczema. A lot of people know eczema, and so you know this, this, it's a small molecule, it'll be it's a pill. If it works people, it'll really help those people with more severe disease. So, so trying to find those reference points that make sense to people.
• 18:30
  John Simboli: Can you recall when you were eight or nine or 10 or some formative stage and you were thinking, my parents, this is as a kid, of course, my parents think I should become a kind of connected to, gee, I'm interested in this. Does any of that have anything to do with how your professional life played out?
• 18:46
  Iain Kilty: It certainly does, to a degree. I think my parents and probably even I as a child, always knew I'd be involved in the sciences somewhere. I was a sort of kid who asked the why question all the time. I wanted to take things apart, understand how they worked. I used to love all the sciences, actually, so I didn't know which path I would follow. Would it be physics, chemistry, biology? It always felt like it was going to be something in one of the in one of those directions, because that was what fired me up as a child, reading about nature, being out in nature. I grew up in Cumbria in the northwest of the UK, and it's a stunning area. It's right by the net Lake District National Park. So used to spend lots of time out in the Fells and so on there and that used to really inspire me, that the again, just being in nature and trying to understand it, geography also. So did I know I'd be in a biotech company? I probably wouldn't have known what a biotech company was at that time. But did I think I'd be doing something scientific?
• 19:44
  Iain Kilty: Probably, that's probably what I would have told you. I want to be a scientist or a doctor or something that has a link to science. But yeah.
• 19:54
  John Simboli: Do you recall at a later stage, when you were in at university or in medical training, whatever's the appropriate part for this question, can you remember, yeah, that's exactly the part of it that I want to investigate.
• 20:07
  John Simboli: Maybe, as a professor, maybe it was an idea that, yeah.
• 20:11
  Iain Kilty: Yeah, so I actually, I did my first degree in Cambridge in the UK. And the scientific degree you enter Cambridge in is called natural sciences. So it starts quite broad, and I actually entered thinking I'd be a chemist. So my first year, I was third chemistry, third molecular work, molecular biology, and then a third sort of zoology type work.
• 20:34
  Iain Kilty: But it was really with a view to chemistry and moving forward.
• 20:37
  Iain Kilty: But actually, once I got there, I got really inspired at an electrical Bruce Ponder, he was one of the guys who identified the BRCA gene mutation in breast cancer. And I remember he, I still remember when he gave a talk about this, and I thought, this is amazing. This is actually the world I want to go into at that point, because this is changing people's lives. He's worked out one of the causes of, you know, familial breast cancer. So it was fascinating.
• 21:02
  Iain Kilty: And really it was the influence of people like him that that moved me from the chemistry focused more towards a molecular biology and biochemistry. And as part of that, I did pharmacology work and so on. I think the other thing that made me think is, I'm probably not a long term academic. I really want to think more about the applied nature of this medical research or scientific research, and then it just, it really just evolved from there, went on to a PhD and then into an industrial postdoc after that.
• 21:42
  John Simboli: If someone says, who is Sitryx therapeutics, how do you like to answer that?
• 21:45
  Iain Kilty: Yes, Sitryx therapeutics are an immunology focused company, but within immunology, we're exploiting immunometabolism to drive a greater anti inflammatory response in chronic, autoimmune and auto inflammatory diseases.
• 22:01
  Iain Kilty: The real potential here is this fundamental thesis around immunometabolism, that by modulating metabolic pathways, we can reset the phenotype of inflammatory cells, so we're not blocking a single pathway or a single cytokine. We're moving the cell to more of a non inflammatory cell type, so that's not immunosuppressive. So that's quite different to current anti inflammatory therapies, and we think offers that potential to drive much greater efficacy for patients.
• 22:29
  Iain Kilty: It's a company that was founded by a number of the leaders in the immuno metabolism space. One of our founders, Luke O'Neill, has really driven a lot of the literature. Jeff Rathmell, Mike Rosenblum, Jonathan Powell, all great scientists working in the field, and that's given us a great basis in scientific knowledge. And then what we've done is combine that with a team who've got both big pharma and biotech experience, certainly within the leadership team, so they know what good looks like, but they can also work nimbly to then be able to exploit that science and deliver novel therapies to the clinic.
• 23:02
  John Simboli: Is there a way to talk about the mechanism of action for the lead candidate for the eczema candidate that you'd like to talk about?
• 23:10
  Iain Kilty: Yeah, so our LEAD program is a PKM2 activator program. So PKM2 is an enzyme that's involved in glycolysis.
• 23:17
  Iain Kilty: It's been a well characterized enzyme for a number of years, but about a decade or so ago, it was shown that as well as this role in glycolysis, this enzyme has a moonlighting role regulating gene transcription within the nucleus of cells. And the way it regulates whether it's driving glycolysis or driving gene transcription is whether it exists as a dimer or a tetramer, so it says an equilibrium between the two in cells, and the dimer will drive the nuclear pro inflammatory gene transcription. The tetramer will drive glycolysis. So our small molecules induce formation of that tetramer, so skew you away from that nuclear activity and maintain that metabolic activity. And the net effect of that is you could, you reduce, particularly lymphocyte T and B, lymphocyte proliferation, cytokine production and antibody production.
• 24:11
  John Simboli: How do you see the lead candidate in terms of your vision for the portfolio as a whole? Where does it fit in?
• 24:19
  Iain Kilty: So our lead candidate has helped us really build our understanding of how to prosecute immunometabolic targets. And one of the things I haven't really touched on yet, but is absolutely critical in prosecuting this target class, is looking at cells in the appropriate cellular context.
• 24:36
  Iain Kilty: And what I mean by that is, if you're growing cells in media with lots of glucose, amino acids, oxygen and so on, that's designed to keep cells alive.
• 24:43
  Iain Kilty: That's nothing like an inflammatory site where the cells are competing with each other for all of those things, amino acids, glucose, and it's often hypoxic and so on. So if you really want to reveal the pharmacology of modulating metabolic pathways, you need to modulate the environment the cell is in and build confidence that's relevant to the inflammatory state in disease to understand the pharmacology. Now our lead program is a great example of that where the pharmacology is only revealed under conditions where the cells have depleted extracellular serines, the amino acid serine, and then what happens is cells need to make their own serine.
• 25:22
  Iain Kilty: Under those conditions, they up regulate this serine biosynthesis pathway. That's when you see the pharmacology of PKM2 activators in T lymphocytes and B lymphocytes. So there's a lot of reasons that's exciting, because that means you've got a very laser targeted approach to it sites where serine is being used up, not just in the blood, where you'll have high levels of serine, but at those inflammatory sites where you're getting competition. But it also provides, if you'd like, an initial way to think about any new target that we bring in. So not every target is going to be dependent on serine. Other targets are going to be dependent on other mediators, and they may be relevant to different situations. So those sort of insights have been important in how we've then prosecuted the future portfolio beyond PKM2. But I say we're very excited about PKM2. There's clear medical need in eczema, and a small molecule, once or twice a day pill that could really drive efficacy for those patients in a safe manner would be hugely beneficial.
• 26:23
  John Simboli: Sometimes, when I talk with folks on BioBoss, I find the discussion is largely around the scientific puzzle, how do I unravel this? How do I make sense of this? How does our company move this forward? And then other times, the discussion will also include, if this works the way I think it will I can't wait, because I can see how this could have an effect on patients. And of course, the two are intertwined. You couldn't do one without the other. But there's like a shifting thing that happens over time in my experience. So where are you on that process? Are you, are you focused primarily on understanding how this all may work. Do you also allow yourself to think about, jeez if this works this is going to really do some good for some people.
• 27:07
  Iain Kilty: Yeah, absolutely allow myself to think the latter. I think that's the thing that makes you jump out of bed in the morning. So if I didn't believe it had that potential, I wouldn't be as excited about it.
• 27:14
  Iain Kilty: I think the potential here is that we can really drive a shift in immune cell phenotype from driving inflammation to more of a homeostatic or non inflammatory regulatory phenotype, and that has the potential to drive sustained remission for patients which which would be huge. Our lead program is focused on eczema, although we do think this asset could have value across additional indications, and there's clear medical need there that there's a real breakthrough a number of years ago when dupilumab dupixent was approved.
• 27:48
  Iain Kilty: It's a biologic that modulates L413. But that that drug, about 50% of the patients get a 75% improvement. So that's similar to an anti TNF in psoriasis. So significant, makes a huge difference to patients, but there's a lot of medical need remaining, and the next wave of compounds were Jak inhibitors. I worked on some of those when I was at Pfizer. One of those is now an approved drug, which is great, and they do give slightly more efficacy because they integrate more pathways than that 413 pathway But there are some limitations around the label and the safety of those assets. So if we could achieve efficacy similar or better, but with a much safer therapy, that for patients would be have a huge impact, and that's what makes me jump out of bed in the morning. I think we have some really nice data to say that that may well happen, but we've got to generate the clinical data to say, is that true? But I truly think that that is exciting.
• 28:40
  John Simboli: Do you see that as a potentially incremental change for patients? As something greater than that? It's going to vary from patient to patient, but.
• 28:49
  Iain Kilty: I think it has the potential to be greater than that. I think it will vary from patient to patient, which is nearly always the case. Always gets some really good responders and some people who are not responding as well to the therapy. But just because of heterogeneity within the disease, but also, there's a huge element of convenience here for patients to be able to take a pill on a day to day basis, as opposed to a two weekly injection. I think for a lot of patients it'll increase access as well. More patients will actually be able to get hold of that drug, I would hope, and therefore get that benefit.
• 29:21
  John Simboli: When you tell the story about Sitryx and people get it wrong, do you ever see a pattern about why they're getting it wrong, even though you said it a different way, they heard it a different way, and then you can help them to get back on track. Another way of saying this, how might people misperceive what Sitryx is about?
• 29:39
  Iain Kilty: Yeah. So I think the biggest misperception we see is actually more on the safety side of things, if you're interfering with metabolism. So getting people comfortable that we're not interfering with fundamental electron transport, chain type metabolism. What we're focusing on are those metabolic changes we're seeing at inflammatory sites, those cysts, those pathways which upregulated to make a TH17 cell more active or or a macrophage produce more cytokines and so on, and to really helping people to understand that by targeting specific enzymes which upregulated at those sites, but also the importance of cellular context that we talked about earlier will drive a very focused pharmacological effect.
• 30:26
  Iain Kilty: So it's not a broad effect that you'll see across all tissues, and that tends to be a place where people can, yeah, they come in, possibly with a bias that I can't see how you could do this in a safe manner. Now, the nice thing we can do now is that we have a program that Lily opted into at IND last year. So we show that we can generate good margins through GLP talks, which gives you some confidence that this isn't a type of approach which can never be safe. And now our lead program is at a similar stage within Sitryx, our wholly owned program, as well, where, again, we've shown good margins through GLP talk studies. Which so I think as we build that data set, people will get more comfortable with that. But conceptually, that can be a challenge early on.
• 31:12
  John Simboli: For the people who like the devil's advocate approach, sometimes the question for the CEO becomes, well, that's a great idea, but if it's such a great idea, how come nobody else did it? So I'm sure you get variations on that from time to time. What's the best answer for that?
• 31:27
  Iain Kilty: Well, I think the science is evolving all of the time, and people actually have focused on immuno metabolism in cancer in the past, which actually has been a good source of targets and certainly tool compounds for us to validate mechanisms and pathways, and it hasn't necessarily been the most efficacious therapy in cancer, but you're trying to do something very different in cancer. In cancer, you're trying to block a pathway to kill a cell. What we're doing is blocking a pathway to drive rewiring of the pathway to different metabolic pathways within the cell and changing the phenotype of the cell. And that's actually what was seen in some of some of the oncology studies. So we've learned from the oncology studies, and then applied that to immunology. So I think it's actually reflective of the evolving science, and that we're part of the first wave there. And then I'd go back to again, that we just have great founders who are a number of the leaders in the field that have helped us move at speed.
• 32:17
  Iain Kilty: And we continue to work really closely with particularly Luke O'Neill and Mike Rosenblum for completely different things, actually, but work closely with those guys as we drive forward our portfolio.
• 32:29
  John Simboli: Who makes a good partner to Sitryx therapeutics?
• 32:32
  Iain Kilty: We're really lucky, actually. We have some fantastic partners at different levels. So going to some of our founders, academic partners, I've mentioned Professor Luke O'Neill a couple of times from Trinity College, we have a postdoc in his lab, but we have joint lab meetings with with Luke, and a really open dialog. And I think that really helps us, because that keeps us at the cutting edge of the academic science in this space, and also helps, from his side, he learns more about the pharmacology, and we're getting great tools, which he can then use in his science. So there's joint benefit there. But the other really good partnership we have is with Eli Lilly. So we signed that deal, actually just before I joined Sitryx, and they've worked with us on a number of programs. They opted into one of our programs last year that was IMD, which they now fully run, and it's in phase one development. And we have a second program we're working on with those guys. And the way that works so well, actually, is that we just, again, we have joint project teams. It's really open between the two companies, and we bring different skills to the table.
• 33:33
  Iain Kilty: So we own the strategy at Sitryx, but it's hugely helpful to be able to pull on the knowledge of the Lilly team and ensure that we're fully aligned as we're moving things forward.
• 33:42
  Iain Kilty: The last thing we want to do is provide a package that doesn't align with their needs. And they're very good as well.
• 33:47
  Iain Kilty: They're not, certainly not obliged to, but they do help generate various data from databases they can access that we can't, that help us move forward more efficiently. So I think the similarity in both cases is that openness. I'm really trying to work as one team with a common goal. The science has to be good. If a science isn't good, then doesn't matter if you put the best team in the world in it, you won't deliver drugs. But you can have great science with a team that's not functional, and you're not going to get there either. And I think the culture that's been built at Sitryx has really enabled the company to move rapidly to the point we are today, and it's just a fun place to work for those reasons. And I think, as well, has facilitated this close collaboration, with a couple of examples I was giving you earlier, around the academic collaborations and the industrial collaborations.
• 34:34
  John Simboli: If I were to ask people on your immediate team, you know, what's Iain's management approach, how do you think they would answer there?
• 34:41
  Iain Kilty: Yeah so, I think they would answer that I'm approachable and very calm. I've always been told I'm a very calm person, which is great. Like to listen to everybody's views, but I really do like to have a decision made. It doesn't always have to be my decision. I just don't like leaving a room without a clear plan. And I think they would probably reflect that ss well in their feedback. And I'd certainly hope, as I said, that they would feel that I'm accessible and they can chat to me. And there's certainly elements of evidence for that that I take comfort from, that that's true. You get bits of feedback, but as we went through the transition, a number of those quite junior team members would come and chat to me about, oh, if in this new role, will I still have chance to ask you about this, and can I share these thoughts or whatever it might be? And I was really pleased that people were willing to come and take some time with me to talk about any concerns they had about any changes within the company.
• 35:33
  John Simboli: How do you know when it's time to make a decision versus when it's time to look for more information?
• 35:39
  Iain Kilty: Yeah, it's a great question, especially in research, because I don't think you ever really know, are you at 60% of the information? Have I got 90 or actually 20? How far do I need to go? So a lot of this, I think, comes from some experience, and also just the importance of the decision and the impact of the decision. So if this is a relatively small decision, it's $5,000 to be spent on study x, or whatever it might be, then I think you can be pretty comfortable making those decisions with relatively small amounts of information. If the decision really could impact the future of the company and the direction you're going to go, and maybe something you couldn't easily undo, then you really need to make sure you've done as much diligence as you can. But I do think one of the things from my experience in both big pharma and biotech, that if you get into a place where you can't make a decision, then you're in trouble, because you've almost made a decision by not making it, you're just static, and if you're not moving forward, you're moving backwards. So I think you've obviously got to be careful.
• 36:41
  Iain Kilty: You're not ready fire aim. You need to give yourself chance to have really thought things through and had the appropriate diligence around a decision that you make. But it can be comfortable sometimes, especially for the more difficult decisions to say, okay, let's get back together in two more weeks, and we'll do research X and come back to this decision. So I just think, you know, you have to be careful, because you've, you've actually made a default decision there.
• 37:06
  John Simboli: Is anything about the origin story and the community that is there in Oxford and in UK in general, that would be interesting for you, in your opinion, to talk about?
• 37:19
  Iain Kilty: Well actually I was in Cambridge, Mass for 10 years before I took this job, so that was quite a different environment. So first I can comment on that. So I originally was in biotech, working with Atlas venture in tech square in Cambridge, and it's a hugely vibrant atmosphere there. It was a fantastic place to first be involved in biotech, and I worked with Bruce Booth. He was the chairman of our board, and again, another great mentor. So again, as I say, luckily, through my career with people I've interacted with in that way. The Oxford ecosystem offers something slightly different.
• 37:50
  Iain Kilty: It's not as developed as the Cambridge mass ecosystem, and we're more spread out. We're not all in tech square. We're at a science park, but there's an incredible amount of high quality science in the UK and excellent scientists, which offer a great opportunity to think about new approaches to developing new drugs for patients, whether that's for Sitryx, specifically within immuno metabolism, or beyond that, in my venture partner role with SV health investors. So I really enjoyed becoming part of that UK ecosystem and starting to think, how can I bring some of the experience that I have from the US into the UK to help us, you know, make more from from the really good quality substrate that we have.
• 38:32
  John Simboli: Thanks for speaking with me today, Iain.
• 38:34
  Iain Kilty: Thanks, John. I really enjoyed the conversation.