The Bioinformatics CRO Podcast

Transcript of Episode 8: Peter Joyce

Grant: Welcome to The Bioinformatics CRO podcast. I’m Grant Belgard, and joining me today is Peter Joyce. Peter, can you introduce yourself please? 

Peter: Hi, Grant. Good to be on. I’m Pete Joyce, CEO of Grey Wolf and co-founder of the company back in 2017. Good to be on the podcast. 

Grant: Great. We’re glad to have you. So, can you tell us about Grey Wolf? What are you doing? 

Peter: So Grey Wolf is a company developing small molecule inhibitors of two enzymes called ERAP1 and ERAP2, and by inhibiting these enzymes, we’re aiming to increase tumor visibility to the immune system so that we can promote the attack and destruction of cancers and act as a novel immuno-oncology therapy. So the company closed series A funding in April of 2018 and excitingly in the last few months just nominated our first molecule that’s now making its way through formal, nonclinical development against ERAP1. And so we aim to be in the clinic in the next couple of years. 

Grant: And if successful, where would this fit in the menagerie of oncology drugs?

Peter: Yeah, it’s a good question because immuno-oncology is certainly a very exciting and hot space, and the anti-PD1’s and anti-CTLA4’s have been game-changing in the area. We see an awful lot of very interesting approaches following up after the anti-PD1 and anti-CTLA4, going after various other checkpoints, for example, or driving activation of the immune system in different ways as well as potential vaccine therapies.

Peter: And whilst, no doubt, some of those will be successful, there isn’t really any therapy looking specifically at the tumor visibility problem. What’s apparent from these checkpoint trials that have been running with anti-PD1 and anti-CTLA4 is there’s a good proportion of patients that aren’t responding to them. Apparently the tumor is not as visible to the immune system, and that’s where we think ERAP1 and ERAP2 sit, is the ability to modulate how the tumor is perceived so that you can promote their recognition to the immune system. And so it dovetails quite nicely with something like a checkpoint, and really gets at that visibility issue. 

Grant: And, how large is that patient population, approximately? If it works amazingly?

Peter: Yeah. So the promise of any ERAP1 inhibitor or the ERAP2 inhibitor in theory is relatively broad. Even in cancer types such as metastatic melanoma or lung cancer where these checkpoint inhibitors have worked particularly well, there’s still a lot of patients that unfortunately aren’t seeing that prolonged benefit in excess of 50% in those diseases where we are seeing really high, high benefit. And then as you move down the visibility spectrum into cancer types that maybe are seeing more like a 20% durable response rate, as you can imagine, there’s a lot of patients there that unfortunately don’t see that survival out beyond one to two years that 10-20% of patients are seeing. So it’s very large. It’s quite hard to calculate, but that’s why there’s so much interest and excitement in this space, because whilst there’s a lot of exciting work that’s happened, there’s a lot still to be done.

Grant: Great. Can you tell us a little bit more about Grey Wolf as a company? How the company works, why you decided to organize it in that way, and how it was affected by all this madness around COVID? 

Peter: Yeah, happy to. So maybe just to introduce the company itself, it’s a company that I started with Tom McCarthy in Oxford, in the UK. We started it in late 2017. I was previously at Vertex Pharmaceuticals as a drug discovery scientist there, and the company itself is, I guess, a virtual company. We don’t have any labs of our own. We operate with a number of different specialists, academic and contract research organizations, and really we coordinate and direct the research. Because you know, drug discovery and development is so multifaceted, and requires an awful lot of expertise.

Peter: That’s a hard thing for a very small company to have all in-house. And we run the company as if it were a project team inside a larger organization, really making sure that all of these different parties, of which The Bioinformatics CRO is one, are all working together with the with the clear aim of trying to deliver these novel therapeutics into the clinic and testing these hypotheses out clinically. So that’s how the company operates on a day-to-day basis. In the context of COVID, we’ve been remarkably lucky, I think. Because of that virtual nature, we do have our own offices because face-to-face contact continues to be very important. We do make a lot of effort to go and see all of the various different groups we work with in terms of trying to build up that project atmosphere.

Peter: So COVID hit us in the way that obviously we couldn’t meet face to face anymore, but we were all very well set up virtually to be able to continue to operate. And we’re very lucky in the sense that it hasn’t really affected any of our timelines this year, apart from things like Zoom fatigue and the usual things I’m sure we’re all suffering from, but we can count ourselves lucky in that. We’ve not had to lay any staff off. The major objectives of the companies overall continue to be met throughout the course of the year, and we’re excited as we move into 2021 in terms of the next phase of the company. 

Grant: Can you talk a little bit about the genesis of Grey Wolf? When you were at Vertex, what led you to jump ship and do your own thing?

Peter: Yeah, it’s a good question. I was pondering this earlier today. I initially came into Vertex as a bench scientist working on actually amyotrophic lateral sclerosis, so motor neuron disease, then moved into more of the oncology space working in immuno-oncology as well as DNA damage repair. Then laterally I was working in rare diseases, which is the often genetically validated diseases, which is the major focus of Vertex now. And through that process, I think I was exposed to a number of other podcasts and avenues that talked about this idea of setting up your own company. I always thought that was something I would like to try in terms of the ability to mold that company’s direction and drive it in the way in which you think it potentially could work.

Peter: Also the idea that a small biotech has that potential to be very nimble, operate very quickly, have very quick and efficient decision-making, and so that had always been percolating over the last couple of years at Vertex. Then Vertex exited oncology in 2017, and there were some interesting ideas in the literature. One of which was ERAP1 that I thought was particularly interesting and worthy of following up, because it was altogether quite different. So the two things really came together, and obviously never set up a company before and it didn’t know how to do it really. I spent my evenings and weekends trying to figure out how you set up a small biotech company. It was during that journey- I think it was in 2018. I was lucky enough to have been introduced to Tom McCarthy who’s the exec chair of Grey Wolf and been very successful in the biotech space, taking a small molecule all the way through to proof of concept in neuropathic pain and then partnering that with Novartis.

Peter: And he was looking for his next challenge in the space, and we decided to join forces. He actually made an initial seed investment in the company, and that’s what allowed me to step out of Vertex, get the company going. Then we essentially became a double act, raising series A or raising seed investment from signatures in addition to the money Tom invested. Then raising series A in April of 2018 and really leveraging all of the excellent contacts and skill sets that Tom has in setting up companies to get the company going, and we’d been working together ever since. 

Grant: Fantastic. What have been your biggest surprises on this journey?

Peter: Probably the biggest surprise is how almost addictive it is running a biotech. As scientists, as we all know, waiting for that next data point is always really exciting. That’s always something that feeds us and is why we do what we do. And then you mix that with the premise from which you decided to go off and set up a company and an ability to finance and get investment into that company. The two come together. Those two worlds come together, and as a result, it’s very hard to switch your brain off because you love what you’re doing. You’re really wanting to push to the next stage of development and investigate whether the idea is a good idea. And if it is, to really try and capitalize on it and push it into patients and ultimately test the hypothesis out.

Peter: So I would say yeah, on a day-to-day basis, that’s great because there’s nothing like loving what you do. The other element is learning. Learning more about my leadership style, learning how to leverage deep expertise across the Grey Wolf team in the various different facets of drug discovery, drug development, and operations to enable us to get the outcomes we want. And that’s certainly a growth within me as I set up the company with Tom and continues to be an active area of development for me, something I think you can always get better at and learn from. So probably those are the two key things.

Grant: That’s great. So Pete, tell us where the name for Grey Wolf came from.

Peter: Yeah, happy to. So as I do enjoy a bit of fly fishing, which I do with my father-in-law. I’ve had many fishless days, unfortunately, but there is one fly that seems to be lucky. It’s called a grey wolf fly. It’s a mayfly mimic, and I thought it was setting up the first biotech company, you know, it’s a bit of a lucky charm, so decided and it was also a bit of a different name. I decided to call Grey Wolf Grey Wolf therapeutics as a result after that fly, although the spelling is different for those who do Google it afterwards.

Grant: That is really interesting. I would not have guessed that. So let’s go back to the very beginning. Where did you grow up? Were you interested in science as a kid? If so, what got you interested in it?

Peter: Yeah. So, I don’t think, during what we call primary school in the UK, I was particularly interested or not interested in science. My grandfather was a keen bird watcher. I do remember being fascinated by birds at a young age and just interested and a bit of a twitcher back in the day, as you say. I think probably my interest in science probably really stemmed in secondary school, and I spent a portion of my time in high school in the US in Atlanta. I had a chemistry teacher, Tony Locke, who was probably really the person who got me very motivated initially. 

Peter: I was probably best at science out of all of the disciplines, and he put it across in a way that I found it quite fascinating and interesting, and ultimately encouraged me to go down the biochemistry route, which is why I then jumped off and did my degree back in the UK. And I think from there, obviously I stepped into the PhD. I fell into doing a PhD in the sense I didn’t really know what else to do, if I’m honest with myself. Then as I started working through that PhD, and as everyone waited till the third before you start generating the specific results or data. It’s two years of no results. That’s when the bug probably started to hit in a way, in the sense of the idea that you’re finding out something entirely novel here that people haven’t really discovered before, and you get to frame the questions that you want to ask. Probably that’s how it started, and then moving into my degree.

Grant: And, on a bit of a side note, what brought your family to Atlanta? 

Peter: So my father worked in the cement business. He’s a chemical engineer by background, always had moved around quite a lot because managing different cement plants and ultimately being responsible for more and more plants, there was an opportunity for him in the States. We actually almost moved to the Philippines before that, but that fell through for a couple of reasons. But then we went, moved to Atlanta and I moved at the age of 15 and came back at the age of 19. 

Grant: Nice. I guess Atlanta is our nearest big city, along with New Orleans. 

Peter: Yes. I guess you’re not too far, are you, actually from Atlanta?

Grant: It’s all relative by American standards. 

Peter: Yeah, exactly. By our standards, this is a long way.

Grant: So what did you do after your PhD? 

Peter: I actually took a bit of a detour. I worked at Wyeth pharmaceuticals in the UK doing something very different, so not research at all. I worked in the regulatory affairs group, working on post marketing. Sorry, post-approval marketing regulatory affairs. I think, probably if I’m honest at the end of the PhD, there’s always ups and downs during that process, and I wanted to explore what else there was potentially out there. I wasn’t really sure of what the next step would be. Yeah, I took that job on, and I think I knew very quickly within the first four months that this was not what I wanted to do. It was really useful and interesting learning about that side of a pharma business and actually probably useful as we move in closer to the development phase of Grey Wolf.

Peter: But yeah, I quickly realized I wanted to get back into research and science, and so from there I went and worked at the MRC in Oxfordshire at the animal unit. I was working on- that’s when I stepped into motor neuron disease, working in a highly collaborative group between the MRC and UCL at the Institute of Neurology and in London. Working at developing novel in vitro and in vivo models of ALS disease was the aim of the project, and so did that for three and a half years. 

Grant: What kind of models?

Peter: Cellular systems, but predominantly it was mouse model systems, and it was using a mutagenesis screen. So the place where I work was a place with Harwell and they used chemical mutagen ENU to essentially drive a whole number of point mutations throughout the mouse genome. Then the job was really to go in and find genes that were interesting in the context of ALS that we knew cause familial forms of the disease. And I try and identify intriguing mutations that have been created through this mutagenesis.

Peter: We found some interesting ones. One gene, we found some in the first gene, so two genes that we know cause the familial forms of the disease. And then the job was to rederive those animals and then phenotype and characterize them, as well as start to understand what are the potential mechanisms by which ALS could be caused in those model systems. The whole premise here was there’s a number of mouse model systems that rely on transgenic overexpression. The fear in this field is always that they could potentially lead to artifactual effects because you’re just driving such high levels of expression. Whereas this way was looking at the endogenous expression of these genes to see. Can you look into a more physiologically relevant environment to see if the pathology is the same as what we see in these other transgenic systems? 

Grant: What about after Harwell? 

Peter: So after Harwell, there was a job advertised at Vertex. I knew I wanted to get back into pharmaceutical research. I really enjoyed the postdoc at MRC, but I knew I wanted to get into that applied research in the pharmaceutical space, and lucky enough that there was a job advertised at Vertex. So Vertex is a Boston based company. They have research sites in Boston and at the time they had one in Canada. They also have a center in San Diego, and they have one in Oxfordshire. And so there was a research site there that was advertising for an ALS scientist to come in and help with the ALS program they were doing. So I applied, got the job, and was working on developing complex in vitro systems initially to try and help with some of the drug discovery programs, as well as driving new target ideas for the ALS programs.

Peter: ALS is a tough area for drug discovery in all honesty, and I think you can see that by the challenging trials and things that are going on. There was a slight refocus, and that’s when I moved into oncology immuno-oncology and DNA damage repair. That site in the UK was really strong in that space, both in IO but also in DNA damage repair, having put the first ATR inhibitor into clinical trials, which continues to do well now. So then, we started learning an awful lot about immuno-oncology, which I found fascinating and worked and led some programs in that space, before then transitioning into rare disease because of the transition of partnering those programs to Merck. Then, I was responsible for helping build the early programs in the rare disease space at the Oxfordshire site and leading some discovery projects there. 

Grant: So looking back across all your experiences and education, what experiences do you think prepared you the most for what you’re doing now and why?

Peter: Good question. I think all scientists go through that period where nothing is really working or you’re faced constantly with negative data. Certainly the first couple of years in my PhD were certainly like that. So I think that level of resilience is really important because you go through a lot of ups and downs in setting up and running a biotech. That is certainly from a personal perspective, it stands you in good stead. I think that also came through- I did a lot of sport growing up, and the same getting used to winning, but more importantly, getting used to losing and being a good loser. No one likes to lose, but I think you’ve got to do it. You gotta get accustomed to it and pick yourself up and get on with it. So, yeah, I think that from a personality perspective is really important. I think that the other key thing that was- it’s a bit of a corny sporting analogy, but it’s also very, very true in drug discovery.

Peter: And I learned quite early on at Vertex was you can never know everything. It’s so highly specialized it’s like being on a basketball team and thinking that you can’t be a point guard, a guard, and a forward. It’s just physically, that’s not possible. So you learn what you can do, but you learn enough about the areas that you can’t do. You know what the questions are you need to ask or where you need to rely on other people. And I think there’s someone stepping out to set up a biotech, particularly in the discovery phase, I was aware of what I didn’t know, what the skill sets I needed to bring in, and that continues now, as we start to move through the development phase. There are people who know more about development than I do. It’s about harnessing everyone’s capability and skills to achieve the outcome, so those are probably two key aspects of spring to mind. 

Grant: And as you build a virtual biotech, how have you balanced what you bring in-house and what you do externally?

Peter: So as we are purely virtual, the emphasis for me initially was trying to build that on the R&D side, was trying to build that project team as would exist in a pharma organization and what we had in Vertex. And so that means you need expertise across each of the scientific disciplines- biology, chemistry, DMPK, safety, toxicology, formulation, CMC at the appropriate points. In the virtual space, you don’t need full time employees across all of those things. You need to have expert people that can fill the various different roles as and when you need them to. A lot of the people we work with work on a consultancy basis, and then we have some more full-time employees or consultants working with us. Then the other aspects, which is really where Kirsty, who’s our chief operating officer, and actually is married to Tom, but has got a deep experience in running tech companies actually over the last 20 years. We needed to be able to operate the company.

Peter: One of the key aspects of having a small biotech was the ability to be nimble, was the ability to decision-make quickly. We make good decisions and if the decisions weren’t good, we can change the decision quickly, and that relies on having an operations area that operates incredibly efficiently. Because you’ve got to go through legal paperwork, you’ve got to go through the financing aspects, all of the investment agreements and everything. They all need to be done efficiently, but to the right level of detail. And so really we lean heavily on Kirsty, and she’s built up that aspect of the organization as we’ve gone along. The two work in parallel, and that allows us to operate efficiently as we go forward.

Grant: Do you think you’ll ever stop? Post Grey Wolf, what do you think you’ll do?

Peter: We’ll probably do it again. It’s the aim. I always really enjoyed time in Vertex coming up with novel or different ways of approaching drug discovery problems or coming up with therapeutic hypotheses that you think worthy of testing and really spending a fair amount of time on that target identification and what is a good target. Stewart Hughes who runs Pathios Therapeutics as a company. I’m also involved with them, we used to work together a lot on that aspect because getting that bit right is so important to everything else that follows.

Peter: And so, yeah, I’ve always got an eye out to the literature and academic groups that we work with and talk to about what could be an interesting possibility of a target idea. Not for prosecuting now, because I think we’ve all got our plates full, but in the future. Because ultimately, it’s not a chore getting out of bed, doing what we do. We’re ultimately trying to make a difference, but at the same time we get to do something that’s very, very interesting. So no, probably I don’t think I’ll probably ever stop.

Grant: Good answer. So, what would your advice be to current industry bench scientists who might be considering doing what you’re doing now? What kinds of skills should they build? What kinds of co-founders should they look for? 

Peter: The number one thing is to be a bit of a sponge and always continue to be a bit of a sponge. You can always do things better. You can always learn. The adage of growth mindset, and whilst it gets overused now, is really, really important. There’s always areas you can be interested in. There’s always things you can find out more about. And it’s not always with a view to you becoming an expert in everything, it’s with a view to understanding how everything fits together. So I would say, yeah, have that level of intrigue and interest. Be curious and absorb as much as you can on the specifics of setting up a company. At least in this iteration of Grey Wolf, one piece of advice I got quite early on from a family member actually was to identify someone who’d been through the drill, been successful because there will be tough times. There will be difficulties. There will be things that don’t go right, and we will know that as scientists, but even on the company and business level, there’s always going to be challenges you’re going to face. So having someone alongside you that has been through all of that before is a great source of help and benefit.

Peter: Tom and Kirsty both have lived that, so that’s a real source of help. A problem shared is a problem halved and all that. So, those are two definitely key things I think you should think about. And then to be honest, the third I would say is the “why”. Make sure you’ve got the “why” right, because there’s times where things are difficult or challenging. You’ve got to really understand why you’re doing what you’re doing. Otherwise, you’ll find it very hard to motivate yourself and get yourself out of any issues and things that you’re doing. You know, I think in our space, the “why” is quite easy. If you’re trying to develop a novel therapy that ultimately is going to help patients, but you can lose track of that at times when things are maybe a bit more challenging or you’re on your 15th Zoom call of the day. But yeah, I think that’s another important thing.

Grant: I guess on that note- you don’t necessarily need to go into specifics if you can’t- but what’s been one of the hardest things that’s happened with Grey Wolf since you started. 

Peter: Probably the hardest thing was, even though I was very, very excited about the next step, the hardest thing was finally saying and actually having those initial conversations with Vertex because it was a company I hugely admired. I had a lot of colleagues there that I really enjoyed working with, and I believe the science was really interesting. So it wasn’t like I was leaving a job that I didn’t enjoy or potentially wouldn’t have a good future in. I had two kids at the time. I have three kids now. At the time, my wife wasn’t working because we just had our second child.

Peter: And so the hardest thing was making the jump and the step, and some people thought I was probably a bit crazy, a bit mad. But it was always something I wanted to do and give it a go. So that was probably the hardest thing from a personal perspective. There’ve been hard things along the way. I think we’ve been very lucky at Grey Wolf. Particularly the ERAP1 project so far has gone quicker than any other project that I’ve been involved in, and the science, for the most part, continues to prove out the idea founded in the literature. So there’s been ups and downs. There always will be, but I think we’ve been quite lucky in the way that’s operated.

Grant: Great. What do you think is some common advice or conventional wisdom that’s wrong or at least that has been wrong in your career? 

Peter: I think probably one thing, and it’s prompted by a book I read recently actually called Range, was in the sector of science, you can get caught up with being a hyperspecialist with really knowing everything there is to know about one thing. And I think that gets drilled into you during your education, really. You get more and more specialized as you go to the point. Though if you start to follow an academic career, you get really stuck down into a niche. And I think the beauty of drug discovery development space is you have to have to lift out of that.

Peter: Although even within that, you’ve got this idea, this notion of a specialist always. You’ve always got this notion of a specialist, and I think in the experience I’ve had today, you no doubt need the specialists. You need them for the particular areas and the particular depth of experience on a particular problem, but you absolutely need the people that range. So people who are able to see the larger picture, can take something from over here and apply it to something all the way over here, which you wouldn’t connect if you’re stuck down in a specialism. And so I think conventional wisdom certainly pushes specialism, but I think we should be also mindful that there’s an equal, if not bigger place for people who can see the bigger picture.

Peter: And I would suggest that that needs to come down further into education in the early phases of education, because you see it with the top academic scientists. Those are the ones who actually are seeing the larger picture and can connect these amazing collaborative networks together and do and ask some pretty fundamental questions because they’ve not gotten down, drilled into this tiny little niche.

Grant: So how do you think we accomplish that? Project based learning? 

Peter: Yeah. Project based learning’s one idea. Broader education for longer, problem solving as opposed to just learning lots of different facts, learning the skills from which to do that. Education’s going that way in a lot of respects. Good question. It is interesting. They talk about the Roger Federer example or the Tiger Woods example, and the Tiger Woods example- being a two year old that picks up a golf club. He was fantastic and was amazing at it, but all he did was play golf. 

Peter: That’s all he did. Roger Federer was pretty good at about four or five sports, apparently up until his teenage years and continues to be a pretty impressive athlete and only really focusing on tennis later on. He exposed himself- or his family exposed him- to multiple different facets for as long as they possibly could until he just chose to specialize.That really does apply to our sector. Those people who are really successful and develop game changing therapies are the ones that can see the bigger picture. 

Grant: So I guess that goes back to being a sponge. What do you think are some of the most effective ways to be a sponge? Some reading on the side on the weekends or trying to get very different work experiences? 

Peter: I think the first thing is figuring out the best way in which you learn. You know, some people learn by reading. Some people learn by talking to people, because that will be the fastest route to which you can be a sponge. You know, obviously we all read the scientists. We have to read publications and everything. I’d probably learn faster by actually having conversations with people and asking questions. I think I was lucky at the time in Vertex because I was able to attend meetings covering a broad range of topics and things. Being a little bit pushy in a nice way to expose yourself to the different facets of whatever sector you are in to broaden your horizons. I also think you can get a bit workaholic. I think giving yourself some downtime, letting your brain reboot, whether that be exercise or whatever it may be, I think is important.

Peter: I think we all talk about it. Certainly there was a period during the first lockdown over here in the UK where I wasn’t getting an awful lot of headspace at all. And then it becomes quite hard to have that “sponge mindset” of trying to absorb and learn lots of things because you’re not giving your head, your brain, the time to download all of the things it’s picked up.

Peter: And you mentioned Pathios earlier. I was just wondering outside of Grey Wolf, what other kinds of things are you involved in and why? 

Peter: Grey Wolf takes up almost all of my time. I do some advisory work with Pathios. I think it’s a really cool idea and interesting idea of targeting macrophage conditioning and modulating the way in which they can go from being immunosuppressive to a more immunostimulatory or pathogenic macrophage. So I’m involved somewhat in that. Outside of that from a work perspective, I’m just really focusing on making sure Grey Wolf delivers, is my primary aim. I think in the future, I’d like to take on some non-exec type roles or, as we were talking about, thinking about what is that next company down the track, but at the moment, yeah, very much focused on the job in hand.

Grant: Makes sense. It’s all consuming. I mentioned this in my email. I don’t know if you’ve had a chance to think about an area in which you think most people are wrong. Or was that the range answer?

Peter: I mean that was what I was thinking with respect to that. There’s this focus on that type of learning. I only think about that with my children now, not just pushing them down one particular avenue, like being a chess champion. It’s exposing them to multiple different things so that they can start to pick and choose what they enjoy and what they’re good at. Often the two tend to coincide. But I did have an episode interestingly during lockdown. I think one of your other questions in the email is what hobbies you have and enjoy. Most sports. I used to play a lot of table tennis growing up because my dad built a table for my old brother in the garage.

Peter: And so I spend most of my weekends doing that. About a year ago we’ve got a garage- or garage, as you’d say in the US- at home and we bought a table tennis table for it. During lockdown, I got quite excited because Will, who’s my oldest, him and I would play probably most evenings, actually. It was a nice way of having a bit of downtime, and he was getting pretty good. He was actually having some very, very good long rallies, but I realized whilst I was really enjoying it, he was trying to not enjoy it so much because he started to get a little bit competitive. I think he got a bit repetitious for him, actually, to be honest, as much as anything else. A part of me is a bit disappointed because you know I love table tennis, could probably play at 10 hours a day every day, but I had to acknowledge that it’s not something that he loves as much as I do quite yet.

Grant: I guess it goes back to letting kids try lots of different things and finding what they like. Hopefully it’s not just some social media. 

Peter: Yeah. Or video games, it’s  constantly video games in our household.

Grant: Cool. Well, hey, thank you so much for joining us today, Peter. It was really great. 

Peter: Thank you. Really enjoyed it. Good to speak to you.