Developing Accessible and Cost-Effective Immuno-Oncology Solutions With Gregory Frost of EXUMA Biotechnology

Startups get the party. Startups get the party started. Startups get the party. Startups get the party started. You want tech and tacos, tacos and tech you know we got tacos and tech is on smash border green guacamole keeper captains counting beans Contador quentan frijoles Founders trying to raise some queso la vida San Diego school of rappy rapping fire tortillas round jalapenos in these modern times a crappy and coffee my coding yoga posse fold the body origami we be surfing coronado eating tacos el gordo the tacos standing puesto lucha libre and sombrero Got a shout out to cost angels by the ocean watch the sunset la Jolla shores Entrepreneurs trying to get funded when San Diego Startup Week is popping in the summer Oceanside, the Tijuana esti be full of hustlers from couch surfing to penthouses right on the beach Tech leaders believe stars are within reach. We interview and founders who be shooting for the moon SD Tecos with your host, Neil Bloom. Startups get the party. Startups get the party started. Startups get the party. Startups get the party started.

Welcome to the Tacos and Tech Podcast. I'm your host, Neil Bloom and I'm thrilled to have you here. On the Tacos and Tech podcast, we interview builders of technologies, of companies, of communities, and we do it weekly. So thanks for tuning in. Every Tuesday, a new interview and on Fridays we talk about what's new in the San Diego tech ecosystem from a news perspective. Welcome back to the Tacos and Tech Podcast. I am your host Neal Bloom here and I'm thrilled to have Greg Frost, chairman and CEO of Exuma Biotech. Hey Greg, thanks for joining the podcast.

Thanks, Neil. It's a pleasure to be here.

Yeah, I'm really excited to chat with you about current state of biotech right now from where you're seeing it, but also kind of where we came from and where we're headed, especially with Exuma kind of at the core around that. You want to give us a quick overview of what Exuma Biotech is all about?

Sure. Well, I think you know the best way to think about Exuma Biotech is it's a molecular engineering company that's driving three horizons of innovation to address some of the most important challenges of cancer, cell and gene therapy. So while the company's just coming up seven years old, that time's been invested in some very exciting multi year programs that are just starting to reach key inflection points. The first Scientific horizon I think we set out on was a relatively specific one, which is whether or not we could engineer cellular therapies to work for solid tumors in a CAR T type format without damaging normal tissue that also express the target antigens. So this one, of course, requires really careful and cautious testing in the clinic, but I think we'll have some very definitive answers on this by the first half of next year for some very thoughtful products that have gone to clinical trials in the past few years. The second horizon is something we started seven years ago, but it's perhaps even bolder than the first and required, you know, solving two challenges before we could even get started. We call it RPOC sub Q. But it's really asking if we can make cellular therapies work without severe immunosuppression or lymphodepleting chemotherapy, while at the same time make it safer and faster to work for patients. So, you know, making a cellular therapy that starts in a subcutaneous injection from a synthetic lymph node, In a way, RPOC's designed to test the first premise of whether or not we can get clinical responses in patients with cellular therapies without chemotherapy. So doing so there was two key areas of innovation there, and that's required getting into specific, specific cell types. But in the end, you know, that as a foundation, is something that takes us to our last line, which is if we can get to these vectors outside the body and actually get them to expand without chemotherapy, then we can start thinking about an even bigger question, which is whether or not we can get those targeted lentivectors to do the heavy lifting and do it directly in the body. So that's gcar, what we call in vivo gene engineering.

Okay. I'm really excited to dive into a lot of the elements here, which we are going to, but I want to kind of take it back to kind of where you began down this pat path. Did you go to school specifically knowing you were going to go down this biotech world and even to run companies? Or what was a young Greg doing coming out of UC Santa Cruz?

Well, what I have to tell you is that when I started Halozyme in 98 in San Diego and it was spun out of the Sydney Kimmel Cancer center, when I just come down from UCSF, I used to joke that when I left in 2014, it was officially the longest postdoc on record. And it really was on the basis of things that I had done at UCSF of cloning this family of enzymes. And I think at the time, the concept that you'd make a company from that, I'd say that, you know, I was really pleased about one thing that we were able to do throughout the time there, which was making technology to help make biologics used around the world easier for people. So in a core area, it was an element, I think that from a platform, technology was something that at the time was very, very novel and.

Okay, so you jumped ahead a little bit where I wanted to go to, which is great. How did you end up actually in San Diego?

Oh, that's actually a very long question. But I do have to say that I was a coin flip away from actually moving to Uppsala, Sweden instead. And there was actually brilliant old professor. He subsequently passed away, but he was on the Nobel committee in chemistry. And I was taking him from the airport in San Francisco to Stanford. And I said, professor Laurent, I'm really considering moving to UPPSOA and working on this program. And he looked at me and says, greg, have you ever been to UPPSOA in the wintertime? No, it's. Perhaps you should. So it turned out that some of the folks that had been out from a spin out from pharmacia had actually started the Pharmacy Institute for Experimental Medicine in La Jolla and said, rather than going to upsoa, why don't we start on these activities and collaborate in San Diego instead? There's a little press release from 1998 about all of this, and that's actually how I ended up going to the Sydney Kimmel instead of ending up in Sweden.

Wow. Our game for sure. But sounds like collaboration continued, so there's good linkages there. What was San Diego like then from a biotech community? Was it. I mean, obviously we have some deep roots biotech. We were just talking about David Hale and like, what was it like?

Well, the beautiful thing was when I started the Sidney Kimmel Cancer Center, Ivor Royston was president of skcc. And so you learn about everything from biotech, the entire history of the town, simply by going upstairs. And so the entire lines From HyperTech and IDEC, all of it was of course, in that neighborhood. But at the time, in the late 90s, there was still a lot of struggle. IDEC was still just getting to a point of figuring out if rituxin was gonna work. And, you know, hybrid tech had turned into after its acquisition and people had spread out to all the other areas around. But I think the beautiful thing was that while it was still a quiet Navy town when I showed up, the amazing thing was that the entrepreneurs that had come, I think, out of hybrid tech and also with IDEC and other areas in Agron that they all still had the excitement to go want to do something again. And so that was really the beautiful thing that made it such a promising environment, despite the fact that people are still learning how to do things. And I think there was certain areas where we still found we had to recruit people in from the east coast for certain things on manufacturing and other areas throughout history. But it's made it for an incredibly vibrant technology hub, I think, for all the things that have been done since then. But some folks take it for granted.

Fair point. I think luckily we have the weather and the quality of life that we don't have to sell people on. Right?

Yeah. And you've got enough biotech in a single zip code that don't have to walk too far. Right?

Right. And people. So which is a recruitment piece where people feel like even if this company doesn't work out, there will be another job for me. But you mentioned the recycling nature. The idea that if we win financially, we continue on and maybe we invest in others and we go build the next thing. That's not necessarily a given. Where do you think that mentality comes from within the community?

I think for the most part that when the biotech community started in San Diego, there were many people that frankly had come from other areas, people in academia and others had been recruited to the location. I think there was a sense of ownership of the community that was built that they wanted to give back to something more on the basis that when I was in. In the Bay Area at ucsf, you know, San Francisco was. Genentech was a mature company at the time. And you had, you know, across the bay between Chiron and others that have been there. But San Diego still felt like the young kid that was growing up. And so I think everyone in the community wanted to contribute to make sure that it continue to be successful. And I think that giving back is something that really helped ensure its success.

Yeah. And when I say give back, which I think you mean as well, it's not purely like charity per se. It's also mentorship.

It's investment. It's people that would go through and say take the time out to sit on boards and help people figure out problems.

And did you feel that with Halozyme? Like, I believe that was your first company, right? Yeah, yeah.

I mean, I found from the standpoint of when Halozyme was started, you know, there was an element of some of the early investors in Halozyme were people that were affiliated with the Sydney Kimmel Cancer center, people that are still, I think, probably many of them shareholders today. But they were all people that, you know, helped mentor people. And I was, gosh, I was like 28 years old at the time, and I sat there and said, I don't have enough gray hair on this. And it started with a great, great professor who is at the Sydney Kimmel at the time. But it was one of those elements that there was always someone that could give you advice about entrepreneurship.

Absolutely. And so Halozyme bit more on the drug discovery and drug development area, Correct? Right.

Yeah. Well, I'd say that. Look, the most important thing that we did, I think, at the time was when we started working on making recombinant enzymes, figuring out a basic model of saying, could we mix these with biologics and make them into simple sub Q injections? That basic business plan was something that when we started, people thought it was very unusual. There were a lot of questions. I won't go so hard as to say crazy. But it was not the obvious business plan. And, you know, the company came out of really a tough world at that time, in the early 2000s, you know, the post.com boom, there was a lot of challenging times for biotech in the San Diego community, but everywhere. And I think the basic business model that came from that, of figuring out how to help a lot of companies deliver biologics and make it easier for patients, ended up being something that, you know, today when we look and say there's many, many patients around the world that are able to actually get medicines, both better access to them and get them more efficiently by doing so. But it was at the time, I think you'd say, it was a different business model.

So coming out, I mean, years later, even decades later, coming out of Alazyme, how did you know you wanted to do another company and where did you set your sights on what would it be?

Yeah, so after 14, 2014, I left and I wanted to do a lot in the of more elements of the next generation of biotech 2.0. And I spent about a year and a half at Intrexone, at Presigen, and done a lot of work on gene therapies and cellular therapies and a lot of great collaborations, and then was spending a lot of time of kind of 500 hours a year on planes flying around the world. And I came to the conclusion I really wanted to focus just on oncology and really decided that that was something that for me Was there was so much to be done that just focusing in that area was. I couldn't sit on the beach for, for more than a couple of months and deciding that I like the beach, but I'm horrible at golf and I'd rather be hunting tumors.

Yeah, I get it. And was San Diego already like an oncology center? You'd call it that, for the kind of the density of companies focus on that?

Yeah, well, I think it was still very early look, a lot of the core innovation, to be fair, much of the early innovation was of a couple of areas between the NCI UPenn and the Hutch up in Seattle. So there's lots of other places that did great work and there's obviously great work that's happened on the San Diego side since then. But those were really the cornerstones, I think, of training where people know you saw that translation coming out in the very early days.

And so was it a bit of a calling the band back together and saying, let's, you know, we've worked together before, let's work, let's build Exuma or what was the beginnings like?

Interesting. We actually went through of the group of people we put together. We looked broad and wide and when we started Exuma, we went through and we had people from San Diego, we had people from Florida, we had people in China came in and we would go through and said, look, the data never sleep. And we managed to go through and, and figured if we could make things move more quickly during the early days of innovation, that time was the most important thing for us. And we said the software industry learned this 30 years ago between Silicon Valley and India and moving code back and forth. So we spent quite, quite a few years just focused on that where we said the one thing we need to be able to hit this innovation is we need to be. Be able to invest more time and make it, make it work.

Oh, that's really forward thinking. And I'm guessing did the capital was capital on board in that regard too, like local capital or where was capital?

No. Well, from A. I think from the early investments that we raised for the company I had from my fund went through and carried the company of, from the Series A line and then from syndicating out with others and people that I'd known obviously of other investor groups from there as though kind of the Series A to Series B, the company's, you know, been very capital efficient. I think to date it's done that on just about 130 million so far. But from that perspective of Kind of moving through each stage we really looked and said for each horizon we're trying to build, we really do need to think about this, of how we can work on each phase of the science so that if we're right, we have a good product or series of products that can come from it, from that platform. But at the same time, when we go to the next successive areas of innovation that they'll also be, can be leveraged in those areas as well.

Got it. You mentioned your fund, which I think is something worth just noting. The kind of the amount of local capital that now exists in biotech. Obviously there was a time where that didn't happen and many of us look around still thinking, wow, there's still not a lot.

No, I think, you know, at each stage of companies from a development side, you know, you look at the cycle and I try and remind people that there's a lot of folks that have looked at, you know, the changes over the last year of the cycle of funding, the shock and you go, it is life on the Serengeti. You go, there are the summer months and there's also the monsoons. But you know, those sorts of cycles that you saw in 2000, it changed the types of business plans that people had and they had to rethink things that were different than the ones that people took on. You know, when the genomic sequencing business model of the late 90s was the new thing.

True. The one thing unique as well in the biotech is going public is not necessarily an exit strategy, it's just to continue to access capital. Whereas that is not the case on tech. Right. On software.

Yeah. I used to look when I was younger, I remember saying to someone, I've gone into exactly the wrong field. Said, I am just getting started after doing research for many, many years and all my friends in software retired two years ago from their companies going public. But I think the element of making molecules into medicine, it is a long term investment that you make and you really have to love doing it. But at the same time, being public is not a destination, it's just one step along the journey. And when you look at the time from making medicine, from the initial steps of discovery, through early clinical development, through registration and launch and you know, eventually through profitability, most people never stay through that entire chain of events. But I do think that that experience of seeing those steps along the way and you spend enough time on the public side as well as the private side, you realize that it's just one piece of the entire continuum.

Totally. Especially like the way you met it, said it, making molecules into medicine. I mean, we're working on changing lives, saving lives, whatever tools, every tool that is available will be used to get there. Because we're working on big things in that regard, like take us through a little bit of car t because obviously that has really been a defining element for a whole industry. Where you guys are headed, it is.

Well, I look back and I say what we started, you know, seven years ago was a basic premise of looking at where the stage of cellular therapies were at the time. And so back in 2015, we were just getting some programs that had demonstrated the inklings of efficacy, some questionable safety at the time still being worked out. And, you know, one of the challenges that were being seen was that the use of these therapies as they advanced from translational medicine, that were being done in academic centers, was a realization of just how hard it is to make cellular therapies on a large scale. And the challenge is whether or not it's were the chain of custody and chain of identity of cells getting from one location to another location and back again, or the fact that a cellular therapy, every patient is a different lot. These were things that we looked at and said from solving these challenges that making this easier. There was a few areas where even in the hematology space where we had seen things early on with CD 19, that to make these easier for patients and for providers, and eventually from an access standpoint, that there was tremendous work to be done, even when you got to those first lines and the first crop of therapies that have made it out through there were remarkable for patients, particularly in the pediatric all settings and other areas where you look at that and say, this is something that makes everyone want to go through and do this nonstop until you've got every patient population you could ever cover. And so what we looked at was of the key areas, the first one we looked at was that if cellular therapies could only work in hematologic malignancies, the leukemias and lymphomas of the world, it would significantly limit the potential of how many patients could be helped. And at the time, that particular challenge, which was the first element we took upon for us, was that if we could figure out how to make cells where they could go after solid tumor antigens without damaging normal tissue that also express those. Those antigens, you have the other 90% of the patients that need these types of therapies if you could get it to work. So that really was the first horizon that we took upon ourselves as a without putting other complex elements behind it, you know, and this required very cautious and careful testing in the clinic. When you look at taking on something as we say, you can live without your B cells, but you can't live without your hepatocytes or lung endothelium, you have to really think carefully about this. And some people have had tremendous challenges there and you have to proceed very slowly. And I think that was an area that we looked at and said that's a very specific question. With the technology we were working on that we were able to get a number of products in. And now we're at a point where we'll have two of those programs that are going up through their dose escalation, where we'll get the cards kind of turned over by early next year and say, is this something that can be done to help a car based therapy recognize friends from foe? And the second piece though, which was in the original business plan, was that element of saying, can we actually make vectors that can do the heavy lifting? And this was the engineering principle where, you know, we call it rpoc sub Q. But it really is saying if we can make this work without severe immunosuppression and lymphodepletion and at the same time get it safer and faster for patients. These are the two things where patients waiting for a therapy to be made or patients that couldn't tolerate the therapies and doctors having a hard time treating them because the side effects of trying to ask is this febrile neutropenia where a patient's running a fever and you've taken away their immune system and you think about it, we're giving patients a therapy right at their most sensitive time for getting an infection. So the thought was if we could get this to work without lymphodepletion or chemotherapy, that would be something that would make it a lot easier to treat patients. Now it's a heavy scientific lift. And we spent almost four years working just on that one question. The second one was at the time when we worked on these lentivector delivery systems, people said that you can't modify with lentivectors patients blood rapidly. And we had a second work stream that we spent another three years on back in 2016 to say, can we actually get lentivectors that will target white blood cells and activate them at the same time? So it was actually these two core pieces of innovation that we had to get working together before we were even at a point of being able to Take that forward for thinking about clinical development.

Wow.

So that one is, is a program that has just now gotten to a point where that one will be going into the clinic next year. And we can ask a very heavy lift of a question scientifically is can you, can you actually get a CR without cy flu? And if you can do that, that's where it's also equally exciting for us because this next level of innovation is that what we call gcar. We've been looking to say if we can get lentivectors to modify white blood cells specifically and do it without lymphodepletion, we may be able to make this into a gene therapy where those products can be administered directly into the patient. And then it's the. You're. As I like to say, if you can get that to work as effectively and safely on that third horizon, then I think you're in a position where you really have no more fundamental platform innovation to do. It's really about helping as many patients as you can. And so we think that's an element that each successive development will create additional opportunity in these fields for others and for us.

Okay, so when you say next year, that's phase two that you'll be gearing up for for the CAR t for.

The solid tumor programs. Those will be through their phase one programs. Okay. Which will let me deciding for multi center trials. Got it. For the RPOC programs to look at the cycle of the questions. That will be a basic element going in on a phase one to say can you get A plus B to happen? But we'll start with some safer targets as well there between solid tumors, as those information read out, we also say, okay, do we bring those into that form?

What's the current state of the FDA right now for a company like yours? Two years, two and a half years later, after, obviously after the beginning of the pandemic. How does that play into the planning for all this?

Well, look, I think that, that we have to look at the, the division, I think from OTAD and cber, the amount of effort that they put forward of herculean efforts during COVID to actually get so many programs of the vaccines and novel modalities through, you know, there was a triage, I think that came through where they all of a sudden had four times the amount of workload to do. And so that's combined with the fact, I think that with the magnitude of the number of cell and gene therapy programs coming into development to fda, that fortunately we're on the cusp of having A new PDUFA funding for them that will give them a lot more resources. So we all look and say, you know, my hope of everything I see with FDA is number one, to make sure they get the support that they need to be able to build the staff for review. The other is helping people on the retention side. Because anytime I see sometimes someone leaving CBER or others, you look and go, there's a brilliant person that has all that experience. So it's a challenge on both sides.

Totally. So what should we be kind of looking for from the community to see, you know, next results in a few years or kind of take us through what you're excited about?

Sure. Well, look, each, you know, I think each step, when we look the first programs that we have in clinical trials collaboration in Asia, those will really be. It's still a traditional CAR T process, but it's using a novel recognition and so working in solid tumors, you know, those types of data that will come out at a scientific congress. The first question is, can you do this safely? Can you do this? Can you help go after targets and better recognize, you know, friend from foe? And I think from that point then it goes into a traditional development strategy which is the efficacy, the safety and, you know, the durability. We look and say cellular therapies require from the benefit you look at for patients is to say, if you have significant unmet medical need that comes into line, then you have to look and say, what's the development program for this? Is this a relapse, refractory patient population? And get into the regulatory discussions, of course, which is, is there a patient population that has the level of need that it's a multicenter single arm trial or is it a multi center randomized trial? And all those things, I think in the field are things that, you know, cellular therapies running randomized trials. The industry has just gotten through the first line of those and it's hard learning and each thing that you do is new. So. So I think on that point, you take each step at a time and you look and say, review the data, you look at the benchmark and then take it from there.

Got it, man. It's for how far we've come as we talk about biotech to then say we're still designing even brand new styles of doing trials and all of those aspects too. It's exciting and exhausting.

It is. But I think that the innovation that's necessary across the board as an industry, keeping the element of patients in mind from having adequate trials that are really asking the important questions and design. My hope is that we'll continue to get smarter and that we're never going to to get to a point of saying that we can't find smarter ways to test medicine for patients and have the rigor behind it to have confidence of efficacy and safety. But I think that the patients demand that you go through and any patient going on trial, you want to do the best that you can do to make sure that their contribution to clinical trial is you're doing the most with the data that come from those patients.

Absolutely. No, I think it's so spot on that you, you are so connected to, you know, the customer. Right. In the end in that regard, it's very easy to work 10, 15 years on something and feel like you're always at arm's length and just working on science. But you're right. No, we're changing. You're literally going to change individual people's well being.

Well, look, I try and remind scientists every once in a while and say not as many mice die of cancer as scientists have been led to believe. And in the end, you go from the process of what we do on all of these. It is very hard work, but at the same time, it's incredibly rewarding work. But it's a marathon and there are no sprints that get you from A to B.

True. So. But still, at the end of a hard day's work, there is still the end of the day and you got to go and, you know, relax or at least go find some good tacos because that's the to relax at the end of the day. Do you have a spot? What is.

Well, I wanted to stretch this question a little bit because if we allow some flexibility on the functional radius where we talk about the best taco spot, you know, I have to go through and say when it comes. When someone really asked me about tacos, I go, we really have to think about our fish tacos in the equation. And if they are, then we need to get the lavi and that that down in Ensenada because we're really talking about fish tacos. You've got to get, you know, you got to allow the radius to get a little better. On the other hand, if you're in a rush of getting through places, Roberto's is always the go to town in Del Mar.

Totally. There's no geographic only spot. While we have actually just turned all of our answers, our database into a visualization so we can tell you how many times every place has been mentioned. And Roberto's is in the top five. Baja has been mentioned many times, usually never by a specific name. It's usually that shack by the guard.

Tower, lifeguard tower, you know, it's that place by K38. Exactly. Yeah.

So no wrong answers there whatsoever. Roberto's luckily is open at any time it feels like, which is happy for that. So cheers to that. Cheers to good tacos and some good surf that goes along with it as well too. Thanks Greg. I really appreciate the time here for what you are building, but also for being able to share what Exuma is going to be going through over the next few years. So appreciate it and keep up the work.

Appreciate all the questions and good discussion about all the fun history of San Diego.

Well, we'll keep writing that story, so appreciate it.

Thanks Greg. Excellent. You take care. Thanks again.

Thanks for tuning in to the Tacos and Tech podcast. You can find all of our episodes on freshbrewedtech.com as well as on Twitter at Tacos and Tech Pod. Also, follow Fresh Breedtech on all of our social platforms and make sure to share and give a review on Apple Podcasts, Spotify or Google Play. Thanks again.

Startups get the party Startups get the party started Startups get the party Startups get the party started. If you want tech and tacos, tacos and tech, you know we got it hey. Startups get the party Startups get the party started Startups get the party Startups get the party started Startups get the party Startups get the party started. You want tech and tacos, tacos in tech, you know we got it Hey.