Science, Startups, and Playing the Long Game - with Dr Jon Moore

Speaker A: Coming up in today's Ideaspace podcast, I

Speaker B: think a lot of people do something to be noticed to make an impact on the world and it's obviously a good idea to do that with improving human health rather than just chasing the money. Generally speaking, one ends up gravitating to high risk ideas where one can make a bigger impact with lower amounts of cash, but you're sort of operating in more dodgy ground about whether it's successful at all.

Speaker A: Welcome to the Ideaspace podcast. I'm Ben Hartley, head of IdeaSpace. IdeaSpace is a community of entrepreneurs, founders and their teams, many of them working alongside each other in one of our three offices based in and around Cambridge. Our AH members share knowledge, experience and expertise to help themselves and others in their high impact venture creation. Today I'm thrilled to be speaking with Dr. John Moore, a scientist turned founder turned biotech leader. John is the co founder and chief scientific officer at Epitopia, a cancer immunotherapy company based in Cambridge and Montreal which is pioneering a new class of tumor specific antigen with the potential transform RNA based cancer vaccines. After a long career and leadership roles at companies like Finalis and Horizon Discovery, he made the jump into entrepreneurship and first co founding Phenotherapeutics and then Epitopia before stepping away from the CEO role in 2024 to focus on what he loves most, the science itself. In this conversation we'll go deep into those early messy moments of building a company. We'll touch on what it's like leading through uncertainty, the importance of building great teams, and why Cambridge is a uniquely powerful place to launch a biotech. Hello John.

Speaker B: Hello Ben.

Speaker A: Thank you very much for coming into um, Ideaspace to do our uh, podcast. Thanks. We're very lucky to have you um, on talking with us. So yeah, thank you. Before we dive into Epitopia, can we start right at the beginning? What were you like, were you the curious sort of scientist type early on or is that something that grabbed your attention later on in life?

Speaker B: No, I was always very much interested in science, not necessarily biology and certainly not molecular biology because that's not readily found in school books or um, or the popular science ones. Obviously I was interested in dinosaurs and volcanoes and things like that. So I would say, you know, in my teens I was considering being a geologist, but an aspiration to be a scientist, whatever that meant, was always sort of part of my character from an early age.

Speaker A: And then you studied biochemistry and later A, uh, PhD. So what was that like early on? Were you fully immersed in that Academic world through university.

Speaker B: Well, I think if one takes it back a little bit further. I was at a former grammar school that had got independent going into A levels as a concentration. I had an inflated opinion of my own ability in mathematics so I was doing double maths. That did not go well. Physics, chemistry, which are kind of dull Chemistry I thought at the time, mainly done so in the A levels. I realized I kind of picked the uh, wrong subjects. And so when I was applying for university I was quite keen to get away from what I was in but remain within a science. And that left the option of biochemistry, which I knew very little about but seemed very interesting. And so I applied to five universities, uh, and got offers from some of them and I went to Bath picking it for industrial placements which were unusual in those days. And um, high A level grades as some sort of barometer of quality which I think a lot of universities an even higher number try now. So I started studying biochemistry uh, in October 1985 at University of Bath, which is a very beautiful place and um, I really, really enjoyed it. It was really interesting. Um, the first year was all new to me even though the rest of my sort of compatriots in the class had all started at Biology A level. And so I just found it really interesting. I like the placements, I like being in the lab making plasmids. Uh, so I did one, what's now ucb, uh, in Slough. I was obviously committed to science rather than nice places to live. And then one in Oxford which actually was even more unpleasant than Slough, um, in terms of where I was living. But I really liked that. I was kind of definitely wanted to do a PhD and it's a question on what and you can apply for a number. And I chose to go to Newcastle in search of big cities and um, quality football. Uh, they have been relegated to what was then the second division by the time I arose. But at that time we could just walk up to St. James's park at five minutes three and get in for four pounds. And so I had full advantages of Newcastle. It was a really great place to live. I had more of a undergraduate like social life for the first year. Really enjoyed it, made some good friends at the time, got in with my colleagues at the department which was quite small and um, started to do proper discovery science in what was an obscure area that no one wants to hear about. But um, after three and a half years of that I got my PhD. I stayed a bit so my then girlfriend, now wife could finish Hers. And uh, I left before she did to um, go from postdoctoral work. So as I uh, indicated my weakness of languages before, um, the United States was an obvious option. Quite a different country in those days. And um, I had a sort of flying around the US on a standby air pass, um, going to interviews.

Speaker A: Did you end up at Duke?

Speaker B: I did end up at Duke, yes. So Duke was like um. It wasn't a good decision but it was a safe option because in the placement course at Bath some of the people who've been on my course had been to Duke and liked it. They did warn me about the weather which was you know, sweaty.

Speaker A: Right.

Speaker B: Um, like it is a bit like it is today actually nothing like it today. It's another order of magnitude of sweat. But so I went there and I was doing some really cool science at that time, uh, with a non cool boss. So um. But yeah that was hitting the big time at Newcastle. There were some people who had been big in the years before and we're now cruising because they haven't, didn't have money or couldn't get the, the top class people. They wanted to compete in international science. But that was no problem at Duke. So I initially um, worked on molecular motors. That was seriously cool. Machines that turn the energy of ATP into motion. I had a project to try and get one that went the wrong way to change direction which I wasn't successful at, though two people later were. And I changed labs after a year um, to go and work for a new professor who's only been there a year called Sally Kornbluth. Uh, she was an American daughter of an opera singer. She'd done a second undergraduate degree at Cambridge and met a um, son of one of the professors in the physiology department and they sort of been together ever since. And she'd come down from New York uh, and uh, a postdoc in San Diego. So she set up a lab and I was their first postdoc. She's now gone on to be president of mit. Oh wow. And but at that time her lab was tiny. The people in it were spectacular. I can't say I taught them everything I knew, but it was a really good time. We work on Xenophus X extract. So it was a system where you had. The frog would lay eggs after being injected with positive um, indications of pregnancy because um, they were used in pregnancy tests. African cloid frogs. And we get the eggs. We'd uh, take the frog aside and go back in the tank with its other froggy friends. And then we'd smash um, the EG up in a centrifuge. And they had amazing powers. Like you could put DNA in and it would form a nucleus, it would replicate the DNA and have a go at dividing it if you let the extract do it. And so we had this powerful system where it only lasted 2 1/2 hours so there was no point in late nights. And uh, that was great. So I worked in uh, the xenopho's egg extract system, doing some biochemical genetics if you like, for about seven years, uh, and three years more at Duke University. And then I'd come back to England in 98, um, to work for what's now Cancer Research UK up at Potter's Bar. You know, it's a forerunner of the Crick Institute. And um, eventually I got a science paper there on um, I did played all the things for the academic cards because that was the career I wanted. So I was working with Nobel Prize winner. I got into a science with a three author paper, three pages long with just one page of supplementary data. And we got the um, mitotic cycling which usually drives mitosis, to do uh, replication instead by fiddling about with how it was controlled and where it was located. So it was just. I was impressed with myself in terms of the science you pulled off, but it was hard, it was hard to do technically and took a long time. So at that stage I was very keen for an academic career. I was applying to, for lectureships in London, Oxford and Cambridge and my money ran out. So I got a job in industry at a company called Riber Targets down in Grants park, now became Vinalys and still remains there. And um, so I came into industry, which I don't think your audience would see as a transition to the dark side in I would say August 2002.

Speaker A: Okay, um, and prior to that, had you thought about anything entrepreneurial at that point? Were you ever thinking about sort of commercialization of the work you're working on? Or didn't that really enter your mind until after you'd, you, uh, know, gone into industry?

Speaker B: So I wasn't thinking of the commercialization of the work I was doing. I did have colleagues who were interested in commercializing, but it was fairly trivial stuff like antibody tags that were alternative, et cetera. What I would say was that prior to doing my PhD while I was still an undergraduate, I was interested in uh, a research career. And I recall when I was in Tim Hunt's lab looking at the demise of big pharma oncology research in the UK with I think gsk, if they were even GSK by that time had moved theirs um, over to the US exclusively and there was only AstraZeneca left, if indeed they were called AstraZeneca that early. So um, I was definitely thinking about it as a possibility but I was kind of out of what it was like. So while as an undergraduate I'd done some work in industry. I hadn't had any more experience um, since then. So I was like nine years out of it. No, 13. And so um, you know, it's a different position so I was always open to the idea of it. But at that point I very much wanted to be the author of my own destiny and all that sort of stuff. And so that clearly wasn't going to happen by joining a pre existing company. So it was ultimately necessity which took me in that direction.

Speaker A: Okay, interesting. So we'll touch on some other startups that you might have had involvement in. But in terms of that first spark for Epitopia, how did that opportunity come about then and what made you decide to just go for that?

Speaker B: Okay, so um, to get to that position we have to sort of skip through a few years. So um, I learned to be a biologist in drug discovery at ah, Riber Targets, which became Vinalis. And I was there for 10 years altogether, um, working out what small molecules anti cancer drugs in particular did to cellular pharmacology, signal transduction. So you're getting this sort of transferable skill set about what's hot and what's not and what's doable in terms of oncology drug discovery, which is of course so much of industrial pharmaceuticals. And then um, I joined Horizon Discovery as a sort of successor to Chris Torrance who'd set it up maybe eight years before. And um, had kind of wasn't having the real influence he wanted in that company. And he had an opportunity to work with the Cambridge Academic to set up the company. It became foremost. So he was already looking for a successor and I was one of the people uh, he trusted and thought was good. So I was sort of seduced in to Horizon Discovery and my race was kind of over at um, Vinales, so I was very happy to do that. And Horizon is a fantastic company. Uh, this was um, in Darren Disney's heyday. He was, he had a good vibe with investors. The company was preparing for a public offering on London markets. It was a real sort of viewed as a success. It had momentum, it had big sales growth, had a lot of good people working there in the lab. And um, at this point the CRISPR revolution had just happened and Darren had been very good at getting some prominent people in the field to join the sab. So um, my role at Horizon really became to evangelize CRISPR Cas9 as a sort of target ID and validation tool to the biotechnology industry in Boston. So I became adept at pitching highly technical things to discerning audiences in small groups, which is the sort of skill set required to pitch VC ideas. Um, and we had a bit of spare cash at Horizon which Darren wanted to put to use in sort of entrepreneurial activities. So we um, we were trying to do a synthetic lethal based spin out, um, to sort of follow Kudios or do something similar to what Archeos is doing now from Horizon using targets we discovered using CRISPR technology. Uh, and so I ended up pitching that to a number of London based VCs and one of them liked me, but they didn't like the idea in its specifics and offered me a job as an operating partner.

Speaker A: Wow.

Speaker B: Uh, okay, so an operating partner, it's a role which sometimes an entrepreneur in residence, it's got different sorts of names but it involves kind of being part of the fund and evaluating usually university ideas which their tech transfer organizations have put forward as a new co idea, testing it out, usually adapting the slides aesthetically, uh, and then developing the business plan, usually giving a bigger budget than the university professors would allow, allowing more time to get to clinic because it's not easy to do. And then um, working out which of these ideas is um, is fundable. And the fundability of a life science company is really about the viability of the exit plan. So one has to look at how it's going to look. VCs as I think most of the audience will know, have to lock up their money for a number of years with uncertain returns and probably a bigger cash demand than they might expect. And um, so you want a reasonable confidence that the project is competitive enough to finish first in a race with an unknown number of players, unknown positions in time starting and um, that the success will be something which will drive a competitive sales process to pharma companies. So um, there's some opportunities that have those sort of characteristics and many that don't. And what works is very much a time and space thing about access to the buyers and, and it being what's required then. And farmer requirements change with time. So generally speaking one ends up gravitating to high risk ideas where one can make a bigger impact with lower amounts of cash. But you're sort of operating in more dodgy ground about whether it's successful at all. So uh, Epitopia was the second company I did um, I think we'll talk about the first one later on but, but it was almost at the same time because it took so long to get going. So this was a case of um, my colleague at Advent, one of the general partners reading a paper in science translation medicine which he read out of interest because the company he founded, Oxford Glycosciences had been interested in this sort of area specific targets on the surface of cancer cells. But as technology was improving, in this case mass spectroscopy, um, the resolution of these techniques and their sensitivity to find things there but there at low levels became greater. And so at the time this paper came out in early 2019 it was possible to resolve sort of 5,000 peptides from um, the surface of a cancer cell population of about 500 MIGs. And um, this sort of study had been done over at the University of Montreal because this was um, I think it was a kind of a second division univers university in the town. It was a highly regarded institute which had some analogies with the curric. We've encouraged to be multidisciplinary in its own building and labs with limited teaching responsibility. And it came out from a long collaboration between an immunogenest, Claude Perrault, former stem ah cell transplant, bone marrow transplant operative and Pierre Thibault who had um, was really running the university's mass biological mass spec core facility. And they collaborated for a number of years on what sort of targets were on the surface of cancer cells. But they'd gone from a bottom up purely empirical response. A fishing expedition as some would pejoratively say. I'm not into fishing but you have to admire an unbiased take on it. At this time I think it might have been the peak of cancer genetics. A number of companies have been set up taking a vaccine approach to come up with personalized medicines. These include Biontech which is still doing that today, uh, Neon which biotech acquired, Gritstone which went bankrupt and a couple of other companies trying to build a fully personalized vaccine Where a company would build an individual vaccine for each patients picking out the best mutations found in their tumor, where they thought the peptides were going to be presented. But what this University of Montreal discovery allowed was an alternative approach. They really couldn't see any mutated peptides on the surface of cancer cells. They were few and far between and arguably at a non useful level even in melanoma where mutations are rife. But fortunately there was something else. Was there a load of cancer specific peptides encoded by cancer specific genes coming from junk DNA as, as some people call it. This was a case where the annotation of all the Human Genome project hadn't been complete. There was this sort of biological dark matter which was encoded in the genome and people knew it was transcribed, but the discovery was actually translated into proteins. And uh, that's trying to digify them because some of these like 20amino acid pieces of trash which aren't even the last five minutes in the cell. But what are they presented among isn't down to how much there is a steady state. It's down to the rate at which they're made because generally that's equal to the rate they're destroyed. And that was the cancer specific material that was found on the surface. So, so it's diamonds in the junk if you like. And there was a lot of sharing. So I thought we could take this technology of the personalized vaccine, depersonalize it and come up with cheap to manufacture off the shelf therapeutics which would be available to patients immediately and um, be the first to do it. Both the general partner Advent and myself, we thought this is a compelling opportunity and we set out to build a company. It took a couple of years to work out what it should be called but we chose Epitopia, um, consciously to rhyme with Utopia. Thomas Moore. Not a descendant, not an ancestor of mine, but does share my name, different spelling. And we had um, Epitope, Epigenetics and various encyclopedia in there as well. So I chose the name Epitopia to capture all of those. And that name had universal appeal with the university founders and the VCs are interested. And then after a lot of hard work, hard work by the lawyers and a big bill we were able to get the company together as a sister company in Montreal and Cambridge and bringing Cambridge Innovation Capital and Advent on the UK side and over in the Canada CTI Life Sciences and fstq.

Speaker A: It's fascinating how you reached that point and we'll jump ahead again just to understand how you might have financed that early element of it. But you'd already co founded Phenotherapeutics by that point which we'd mentioned earlier. So did that experience for you change the way that you approached building Epitopia?

Speaker B: Not so much because I was doing both at the same time. Because Epitopia took so long to get going. We thought of the idea and by uh, the time I um, got the Funding. I'd already been CEO of Phenotherapeutics for two and a half years. Ah, so I wouldn't say the experience of one influenced the other because they were kind of simultaneous. So Phenotherapeutics was an Edinburgh University spinoff. So Advent are one of those rare cases. Company forming VCs, uh, operating on lower budgets than third rock and flagship, but aiming to compete in truly innovative companies. Of course done with more capital efficiency. Uh, Edinburgh University had pitched a number of ideas to Advent, um, maybe a year and a half before I'd arrived. But Advent didn't really have a funding vehicle available. So as soon as I arrived we went on a tour of Scotland to Dundee, Edinburgh and um, Glasgow to look at what was available to sort of keep our contacts warm. M But the centerpiece of that trip was a pitch by Siddharthan Chandran, who was a London origin medic, who was big uh, news in Scottish neuroscience, and Neil Carragher, who was really cancer focused phenotypic screener. Uh, they got together to come up with this idea of phenotypic screening for compounds that would um, be predicted to remyelinate neurons in patients with Ms. And we thought this was an idea whose time would come. So um, Phenotherapeutics was their choice of name. Uh, we sadly vetoed the original Jaga Therapeutics. Uh, I'm not sure if that was a good idea, but we thought that could be off putting to some other investors to have this obvious Rolling Stones referencing what we're doing in our spare time. So we went for the rather more sedate Fino as a name and Advent funded it towards the end of, towards march, uh, 2019. So I was the founding CEO. It was a two day a week job, but that was different. That was really a university project which was run with university scientists in the university. And my job was really to pay the bills and look at whether our assumptions about which pharma companies would be interested in it were true. So that project was pretty soon interrupted by the COVID pandemic which did uh, make it difficult to do lab research, especially lab research as complicated as this. Uh, so Fino continues. I stepped away in March 2022 and I left them with a present which is now their lead assets. Um, so while Fino was, as the name suggests, a phenotypic screening company, that of course is not the only way to um, make progress in therapeutics. And as an alternative, um, of course one evaluates the competition for every board meeting. And so it was clear that there was Some um, genetically validated targets which uh, when knocked out the mice in this case are viable but they just remyelated their brains a little bit quicker. They don't go too far, they just do it faster in development. So this was an interesting target and I was looking to see if any university or any drug discovery company even better made any progress in this. So I was really looking for any sign of industrial activity against this target. And eventually I got a hint that UCB in Belgium may have had a really serious go at it. And so I contacted them. It took months and months to get a reply but eventually I was handed through to the right person and um, we were able to uh, after quite a few months and me already having left in this time, we were able to execute a deal for Pheno Therapeutics to acquire what would have been the work of I'm guessing 100 person years of medicinal chemistry. And the price is undisclosed. But it was low.

Speaker A: Yeah, yeah, but a uh, success in the sense that it was uh, gone full circle for you.

Speaker B: Yeah. So uh, the scientists who took over running for Pheno for me were far more adapted to a neuroscience company or experts in the area. We now have one of the original UCP compounds approved for clinical trials. We have um, backup compounds which have been discovered by um, fino funded research to go in and that company is just waiting the cash and it can begin first uh, time in human trials almost within months.

Speaker A: Yeah. Great. So we're now back with Epitopia and um, concurrently. And it took a long time as you've said. But how did you fund the early stages of Epitopia then?

Speaker B: So uh, Apitopia's early stages of setting it up were funded by Advent. Advent were paying me. I was working a day and a half, a week on it for about a year and a half building a business plan, uh, working to uh, get the investors in and then working with the lawyers on uh, a complex exchangeable share structure linking the Canadian company operating under civil law in Quebec with a common law organized UK company headquartered in Cambridge. And um, we spent quite a lot of money on the um shareholders agreement which regulates the company, how it works and understanding the tax implications of various exits. So we ended up in a situation where the two companies can lend each other money, uh, they can charge each other services, um, so we can have a clear sort of tax, um, residence of various projects. Uh, we set it up so we could claim R and D tax credits in both jurisdictions. Um, but in terms of an exit, we can exit as two separate Companies, as long as the buyer is the same and pays the same price. Or we can combine the day before, uh, into the UK company.

Speaker A: Wow. So obviously that's quite a complex, um, setup. Complex for many people, uh, who don't know.

Speaker B: Oh, it's complex for me as well,

Speaker A: who don't know about it. So you obviously got very good advice. But was that based also on experience that you'd picked up?

Speaker B: I think it was. To do this wasn't a choice, but it was the only way to make it happen. And I was the kind of point man putting it all together. Half the money came from England, half of it came from Quebec. And Advent needed a UK company, um, because a certain fraction of their fund has to be invested in UK companies because the British Business bank are a cornerstone investor. Uh, Cambridge Innovation Capital needed a major presence in Cambridge. So the way to satisfy all of these was to have both a UK and a Montreal company and then we had to link them in some way. So there's a sort of common board, it alternates board meetings between the two countries and we don't think it will be too scary for a buyer, um, to buy both companies together and we can combine into one the day before, if need be.

Speaker A: Great. Just focusing on Cambridge, what do you think makes it such sort of fertile ground for biotech companies? I mean, beyond the obvious that the

Speaker B: universities, you know, it's the reason why the workforce are here. It's a hub. I think the move of AstraZeneca into the area from Audley park and Charnwood, I suppose came back further, has been very helpful for the, if you like, worldwide pharmaceutical profile of Cambridge. But it was already very strong. The nature of a hub is that it becomes safe as an employee to work for a small company which might only be here three years because there'll be another one you can walk within 10 miles that you'll be able to, uh, move to if they like you, without moving your whole life around. So I think, um, hubs arise where they are historically and they're very sticky things. So clearly the university, Cambridge University has made a massive impact in 20th century life science, which it continues to do,

Speaker A: I was going to say also the organisations that sprung up around it. Obviously there's Cambridge Enterprises, that tech transfer office and innovation arm, um, of the university that's grown massively just in the last 10 years as well. So that an idea space and all of the other organizations here that that whole ecosystem is built up with it. It's not just the university.

Speaker B: I think, um, The Cambridge University sort of allied organizations, CIC as well, I um, think they're responsible for about half the bandwidth of the ecosystem. There's an independent side of it which kind of rests on the history of Cambridge to be located there. Companies that I started off working for Riper Targets was an LMB spin off which had changed direction. But yeah, that was a University of Cambridge affiliated organization funded company. Then you had Cambridge Antibody technology across Grounds park, that was another one. And so I think you could say AstraZeneca's location here built on the success of MedImmune and therefore Cat. And so the university, if you take a long term view of it, has had a massive impact on, you know, life sciences employment which is massive in Cambridge. And um, it is, I mean I spent for many years not being involved in the harbor. I was right out in the periphery at Grantham Park. And then when a company is 100 people you tend not to have strong networks with organizations like Cambridge Enterprise and One Nucleus etc. But for smaller companies a lot more important it provides that uh, sort of critical mass of socialization. So you're not like three people in a Ford cabin, you know, completely on their own. Like if you set up a company in Devon.

Speaker A: Right.

Speaker B: Be like. And yeah, we saw um, occasionally I think some of the chemical suppliers tried to launch Construct Discovery in Cornwall, but I don't think they got very far.

Speaker A: Yeah, I was going to say that's why communities like Ideaspace are important for those small individual companies. Oh, and I didn't say you were um, actually an ideaspace member at IdeaSpace south, weren't you as well?

Speaker B: Yeah. So um, from my personal perspective we were coming out the pandemic, so I hadn't done any socialization with scientists or anyone else for a very long time. Cambridge Innovation Capital said there would be space at the Milner Therapeutic Institute, which was very good in concept as a lab because it had fantastic equipment that had all been bought and you could access it for effectively £3,000 per head per month. So that was invaluable for setting up Epitopia because we needed expensive equipment and we didn't have to buy it as one off pieces and spend a lot of money on Capex because we could use or share the equipment was really there. IdeaSpace south came into its own for several reasons. Um, at the time it was quite, there was a lot of space which meant a lot of chances of getting a meeting room without needing to book it, which is important for my lifestyle. Um, and it was very very close to MTI as well. So I think there was something about IdeaSpace being in the LMB, where so many scientific greats had walked in the past and so many big discoveries have been made there, but they'd moved to other side of the camp. Uh, the building is one of those ones that you go, is this really distant? But, um, I think IdeaSpace was great for me because of the location. I like the staff working with, um, Ben. Hello, Ben. And with Kirsten as well. And there were a lot of efforts being made to have an entrepreneurial network, which I didn't make that much advantage of, but would have been invaluable if I'd been less settled in Cambridge.

Speaker A: Thank you. More recently. So obviously Epitopia has, uh, grown. I was going to say quickly. You'll say slowly, but it still feels quickly. And then obviously, uh, you made the moves to concentrate on what you clearly are so keen and passionate about, which is the, uh, science side of it, becoming the chief Scientific officer, which you're doing now. Um, what did you sort of learn during that, uh, transition?

Speaker B: Well, I think one thing I do know is that the more people you have in a company, the more conversations trying to have with third parties, the more complicated it is. And, um, it does become too much. And one needs to bring in experienced people with a focused role. I think in my dreams and also the investors dreams, I would have been spending all of my time engaging literature in lab meetings, discussing things with science. But there's a hell of a lot of admin to do, you know, to make sure people get paid. And, um, that we're adhering to employment law, uh, we're dealing with, um, career development issues, which is not. Which is interesting and a pleasure in many cases. But I don't spend as much time on the science as I thought I would. So what has been great to see is that the people I've hired have been doing that and really been growing into what we're trying to do. So to be specific, we're trying to be world leaders with a team of 15 people, mostly in their early 30s. And um, they've got to be good and they've got to become better, support us off. Because we're competing with Moderna and Biontech.

Speaker A: Yeah.

Speaker B: With um, 10,000 times the amount of money we have in the bank. Or is it just a thousand? But they certainly have 100 times as many people. And so, um, so we have to be intelligent now. Choices. We have to, um, learn from what they've done, find a better way to do something similar and take advantage of all of that. So what I've tried to do apotopia consciously is to get a good team which I think will work together and give them the freedom to explore and not have a pyramidal structure where every piece of information has to come up from its silo through me down to the other one. And um, I had a meeting with a colleague this morning and I think that's gone very well. And really in the last sort of few months I've seen this enormous growth in the capability of the team and they've really done this themselves up the skill set, behaving in a better and better way and becoming really, really close knit. And I've certainly tried to do this, but it seems to be more successful than I deserve, uh, given the effort I put in. And I'm looking at it and go, whoa, what have I created? This is amazing.

Speaker A: That's fantastic. Um, what an excellent way to be able to think and to know that, um, you're being incredibly modest having built that team. But, uh, to have that much trust and faith in the team and to

Speaker B: see what you've built, I think trust and faith is essential. To get anything done. One has to delegate. But really we've got operating principles for how we should work with each other and a clear mission of what we're trying to do, of which patients are at the center, as most companies would say. But what I say to every biologist coming in is your job at Episopia is design the next human therapeutics. You and two other people can do it together. You know, we're world class what we want to do. You've got a chance to help us take that final step to galactic level excellence. You have the chance to design a therapeutic on this piece of paper in front of you. You're not, you're working for a chemist, seeing if a compound works. What we're trying to do, we're working from antigens which are cancer specific, uh, transcriptional and translational level. The safety risk is low. So it's not like small molecule drug discovery where you need across the project, 50 person years of effort to understand tox liabilities, et cetera. Most of that has been worked up earlier in terms of the, um, you know, the antigens and the way they're picked out by UDM for selection. And so we just have to put them together, just have to put them together in the right order, in the right context, build a competitive vaccine platform. But there's this sort of ownership of therapeutic design. Which I think is enormously attractive to biologists. It is to me. And um, because I'm a generous guy, I let the team do it all. And I think they thrive on that. So we've got a very high hit rate of interviews to acceptances. And, um, we have a strong team, which is very female heavy, which is

Speaker A: fantastic in stem cells. My daughter's just, she's desperate to go into biology. She's first year of A level and I couldn't be more excited for her.

Speaker B: Uh, well, I can guarantee it won't all be done.

Speaker A: So for listeners who might not be totally immersed in cancer biology and understand a lot of it, much like myself, can you just, in very basic terms, talk about what epitopia is, is doing and why it matters? I know for the, for the scientists who are listening, they will know of you and understand that.

Speaker B: Yeah. So, um, I think there's been various schools of thought in cancer biology over the last century and a half some. And so if you talk about what can really make a difference to the burden of mortality and morbidity it places on societies worldwide, there's various sorts of, um, ways you can look at it. So it's a disease of aging. And as the global population gets older, there'll be more and more cancers. Um, even if lung cancer largely goes away because of smoking cessation, there's plenty more of lifestyle things driving incidences in cancer. So more and more people are going to be affected. And it's something everyone, once they're past a certain age has heard of. They know it's a bad idea, bad thing that can happen. It's a worry. M. Both my parents have various sorts of cancers, but neither of them were captured by it, at least not directly. So it's um, I've always attractive because if I'm successful, people go slap on the back and go, yeah, well done, John. That was an important contribution. But then how it's done is into the detail specifics. So I think from through the 90s and you could say, and 2000s, the leading sort of approach was to develop small molecules or antibodies against the drivers of cancer. Things like imatinib gleevec for bcr, abl, cml. You know, we've had small molecule KRAS inhibitors, um, which is a massive technical success. And all before that were antibodies against the HER2 target. So there was this big current of trying to move away from chemo into, let's say personalized medicine, where 15% of patients would be able to take a particular sort of targeted approach. So um, but another, there was always a group looking for new global treatments to cancer. Cancer metabolism was a sort of failed idea in that direction, or at least failed so far. Um, cancer epigenetics was another one, but the one that made it, or at least partially was immunotherapy. So this is uh, an old observation by William Coley back in the very early years of the 20th century, if not earlier, that some patients who had horrible fevers ended um, up curing their cancers. So there seems to be this sort of um, interplay between cancer and immune system that if a patient has a cancer, the immune system probably had an opportunity to deal with it, failed to deal with it, but still, you know, is being held down by the cancer, ah, to ignore it. So there was various insights to um, sort of exploit this. And this led to the discovery of CTLA 4 and PD L1, which are uh, I suppose immune checkpoint genes. I might generalize too much, but you could say these are things that the placenta and the baby used to hide from the mother's immune system. Obviously there's a lot of genetic differences between parent and child and um, with a child living inside, a parent has to uh, find a way around that. But cancers can co opt these mechanisms. And the insights of Jim Allison and um, a Japanese guy whose name escapes me who discovered the real big one PD one were through and M. They both won Nobel prizes in 2018 for their work. Um, now a company that one of my colleagues at Advent had found, founded Medirex, had worked on CTLA4 and PD1 antibodies and got acquired by BMS. And so that was one sort of current in immuno oncology. And then work by Ono and um, uh, Shearing Plough and Organon in one of their sites came with the other antibodies which were acquired by Merck. Pembrolizumab. So pembrolizumab and to some extent ipilumab, BMS's equivalent, have become the biggest selling drugs in the world as a class. Um, before GLP1 antagonists came along. And um, they have the difference they have to previous cancer treatments is that while a lot of people benefit a bit, there is a sort of tale of patients who really benefit and get cured. So I think uh, Jimmy Carter had melanoma, he had ipilumumab. He just had it once because it's horrible. But his cancer, his melanoma was cleared up by it, just by one injection. Now that's a rare response. But the thing that's attracted me and Everyone else to it was that you get really durable responses to this. So what epitopia is, it's one of many activities in the world to widen the number of patients who benefit from immunotherapy. If you like having immunotherapy for the many, not the few. And there's been many ideas tried to take these response races from 20% to 60%. And um, we think obviously that we've got the best approach to it. And what we're trying to do at Epitopia is educate the immune system to become aware of cancer antigens. It's ignored before because of technical reasons of presentation. So we're going to deliver the antigens as a vaccine using LMP MRNA technology that's going to be injected into arms. So it'll be a peripheral immune response like it would be to uh, an infection. And then the T cells raised, they're mobile creat and they'll go and find the tumor and deal with it. So on its own that sort of approach is unlikely to clear up a big tumor. But there's many cancers in which post surgery and initial chemo the tumor is small, in remission and in abeyance and we want to get in that opportunity and stop it coming back. That sounds, it sounds quite difficult and in many diseases it might take a while to show positive results. But, but uh, the advent of circulating tumor DNA and also some diseases recurring ah, quite reliably unfortunately quickly gives us an opportunity to pick a number of cancers where existing treatment options are uh, either ineffective or intolerable or both, come along with something which is merely inconvenient and um, deliver what we hope will be long term remissions. Ah so I think Moderna's results in melanoma suggest that this is possible. There are other, other situations where all cancer vaccines from the past uh, have been tried prior to surgery in breast cancer and half the death rate. So I'm pretty confident that the approach will work. And I think epitopia's um, particular take on it is um, is one I'm very happy with. And you know I am a scientist who goes to conference, look at other people and go oh God, I wish I was doing that. That's really cool. But I don't think that anymore.

Speaker A: What you're doing is very cool.

Speaker B: It is, yes. And so I'm very happy with it.

Speaker A: Yeah.

Speaker B: And I'm a self critical person and uh, I thought, you know, what we're doing is very cool. I think it will work and I think it will Be affordable.

Speaker A: Yeah, amazing. Um, it's incredible to hear from. Yeah, it's funny I say early, it's not early stage. And it takes a long time to get to this um, point for you. But uh, what are the sort of next milestones then for you?

Speaker B: The next milestones? Repertopia is we have a bigger C level team now. We've got four of us in four countries actually. So we've hired a Klaus Edvardson, who's worked at two cancer vaccines in the past with AstraZeneca in Cambridge. Other big pharma companies, well respected in the field, has run trials and we're taking our vaccines. Uh, our first product, you know, is for gynecological cancer and we aim to be in the clinic within the next nine to 12 months. So hopefully by the end of March next year the first patient will have been dosed with our vaccine. We're manufacturing it in Calgary. And uh, so there's big milestones are ahead. So there's a long way to go for Ethotopia as a company and both off the shelf cancer vaccines as a field. The future is very exciting, uh, in

Speaker A: both those respects, incredibly exciting. And we'll have to obviously get you back again. I know we don't have massive, um, amounts of time left, so can we get you back at the, the next stage? Which would be amazing. I uh, just really in the last sort of few minutes I'd love to be able to just get your thoughts on, on some of the um, almost like the impact has had on you and the learning experiences of this kind of journey up to this point and what you might sort of pass on to um, other people who are at a very early stage, as you were, uh, you know, three, four, five years ago.

Speaker B: I think it's um, it's difficult to generalize about. Anything that's worth doing is often hard, either intrinsically or because it's competitive. I think because a general experience is a failure, frustration or deferred success at best, um, one has to be prepared for a bit of a struggle. And then the question is, you don't get anywhere by giving up, but you don't want to flog a dead horse or use too many cliches in conversation. So it's uh, I think having good advisors, both peers and more experienced people about when to carry on, when to give up, what you're good at, what's a weakness. Because weaknesses can be complemented. Sometimes they can be overcome personally, but in many cases you're more successful as a team. Large or small. So I think to anyone who wants to make a difference, there's a certain pleasure in taking an idea from your head into reality and having, in case of Epitopia, 25 employees or not. And uh, I am proud of it and it's a good feeling so it's worth persevering. But I think anything that's successful has to be differentiated and not have um, too many obvious competitors. It's nice to have some for socialization and to, you know, that can try out other ideas which you thought of and see if they work or not. So um, the advice is to be a good listener, uh, be very honest with yourself about how things are going. Work hard, but not so hard that you don't have time to come back up and ask a big question about is this something I should be doing? Or do we need a bit of a course change? So I mean being your own boss is you never, only never really your own boss. Few people can do or no one can do anything that's unconstrained. So I think it's finding the right amount of freedom and um, autonomy that sort of balances obligation and um, uh, self realization. So I think a lot of people do something to be noticed to make an impact on the world and it's obviously a good idea to do that with improving human health rather than just chasing the money. So I think it does, um, it's obviously a privilege to try it. It's lucky to be reasonably good at it. This is certainly a great time to be a biological scientist and um, there's lots of discoveries to make and there's lots of translation of that into human health, but we'll see. So, um, I don't know how much I've learned really.

Speaker A: It sounds like a lot like from, yeah, from, from where you're sitting it might not feel like it, but from where I'm sitting a hell of a lot. John, thank you so much for um, coming in to talk to us. This definitely needs a, um, round two because where you, you will go with this and where you'll take it could be life changing for many people. So um, on that. Thank you John.

Speaker B: Cheers Ben. That was fun.

Speaker A: For more information or any inquiries about joining Ideaspace, please contact us via ideaspace.cam.ac.uk or via any of our uh, social media channels.