LifeSci Gritstone Podcast
Below is the transcript from LifeSci’s podcast with Gritstone CEO, Dr Andrew Allen. You can click here to listen along side the below transcript. The programs referenced in this podcast are; Granite, Slate, and Coral. For additional transcripts, due diligence and more on Gritstone, click here to view our page on Gritstone which has gained our core position status with a high allocation level rating.
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Neil Canavan (LifeSci Partners) 0:02: Certain information set forth in the podcast may contain forward looking statements under applicable security laws. These statements are not guarantees of future performance and undue Reliance should not be placed on them. Although forward looking statements contained in this presentation are based upon what management of the company believes to be reasonable assumptions, there can be no assurance the forward looking statements will prove to be accurate by say advisors and the company undertake no obligation to update forward looking statements in the podcast should circumstances or management’s estimates or opinions change. This podcast is for general information purposes only. It is not an offer or solicitation to buy securities and does not constitute investment advice.
Dr. Andrew Allen (GRTS CEO) 0:41: In roughly half of our colorectal patients, we were able to see evidence of molecular response the CtDNA went down and those patients remain free of disease progression and the live much longer than you would expect a much longer than we saw in the patients who didn’t achieve molecular responses.
Neil Canavan (LifeSci Partners) 0:59: Hello, my name is Niall Canavan and this is benchtop bio podcast series but life side partners where we introduce healthcare investors to the people and the pipeline’s driving the tech sector forward. Today, it is my pleasure to introduce you to Dr. Andrew Allen. He is the founder and CEO of gritstone bio. Andrew, welcome to the podcast.
Dr. Andrew Allen (GRTS CEO) 1:23: Hi Neil. Thanks for inviting.
Neil Canavan (LifeSci Partners) 1:25: So first things first for the benefit of those who may not be familiar with gritstone, let’s start with the elevator pitch nice and short. Andrew. Where is gritstone headquartered, how long have you been there and give me an idea of what you’re doing there?
Dr. Andrew Allen (GRTS CEO) 1:37: Gritstone six years old, around 200 employees. We’re headquartered in Emeryville, which is at the eastern foot of the San Francisco Bay Bridge. And we have a manufacturing facility in Pleasanton, which is a town about 25 miles further east. And we have a meaningful group in Cambridge, Massachusetts as well. We began life as a company dedicated to finding targets for T cells on cancer cells, and built a few platform components to address that goal. Firstly, an ability to identify which parts of a target can be identified and recognized by a T cell. And then we develop to vaccine vector systems that will drive strong immune responses against those targets. And we have both a self amplifying mRNA platform and an adenovirus platform. We’ve applied those elements now to both oncology and also to infectious disease, and infectious disease, which we’ve announced more recently. We have a collaboration with Gilead around HIV. We have our own product in the Coronavirus, COVID space. So we’re
Neil Canavan (LifeSci Partners) 2:37: going to find more detailed download on gritstone in just a few minutes. But first in keeping with the mission here at benchtop vial, which is introduced listeners the senior management Let’s talk for a bit about you. So starting with your training, you are a physician. You achieve your medical training at Oxford University circa 1990. You hang out your shingle for a few years and you did practice medicine. But then, much to everyone’s chagrin probably arrived, maybe your mother you went back to school you got a PhD in immunology. This would be at the College of London, circa 1999. So two questions. Have you ever been to the eagle and child? And if so briefly describe it for our listeners.
Dr. Andrew Allen (GRTS CEO) 3:15: For sure. The eagle child is a famous pub in Oxford where CS Lewis and Tolkien used to debate life on a regular basis. It’s set on Broad Street in the heart of Oxford, surrounded by many other equally historic pubs, but that one has a particular place in history, I guess. So for sure, yes, I spent much time there. It’s a classic English pub, flagstone flooring, wooden counters, pretty basic stuff, but a good place to spend an evening particularly in a cold winter.
Neil Canavan (LifeSci Partners) 3:44: I was lovely. It’s a real step back in time. So the second question for pertinent to our conversation today. And this is sort of a two parter. First, why go into medicine? And then second, why did you double down to pursue immunology.
Dr. Andrew Allen (GRTS CEO) 3:57: Medicine just was a passion from early on in my life. The notion of exploring science helping patients was just a powerful motivator for me from a pretty early age. That was my path. And when I was a med school in the mid 80s. In Oxford, we spent an extra year doing some basic science and immunology was really hitting its stride at that time. So in the post war period, Peter Medawar, and the team up in Mill Hill in North London had done some fascinating in vivo immunology, linking animals circulation together and looking at how cells were interacting with other related or foreign species the notion of send generic and Xena generic and so on allogeneic all of this was worked out using sort of physical observation in vivo experiments. And then this was reduced to molecular immunology and a much deeper understanding of why these phenomena were occurring. And so in the mid 80s, the T cell receptor was cloned the notion that T cells don’t recognize whole proteins and instead, they recognize short peptide fragment displayed by these highly variable HLA molecules, and that those were the targets of T cells. This was all unfolding real time for me. And it was such a fascinating science really, that the door was really opening to something you knew is going to become incredibly important, both scientifically, but also almost, certainly therapeutically.
Neil Canavan (LifeSci Partners) 5:19: Well, even at that time immunology was they were just opening that black box, if you will. Were any of your professors talking about oncology, as it related to immunology,
Dr. Andrew Allen (GRTS CEO) 5:29: There was a little Yeah, I mean, not in any great depth at that point, but for sure that inflammation and cancer have been linked, obviously, for many years. And so as soon as you start to study immunology, you’re into that domain of inflammation and cancer. And what you learn in one domain usually has relevance to the other. So this has been in my world for a long time.
Neil Canavan (LifeSci Partners) 5:49: So the next move is a bit puzzling to me, you wrapped up all that education 1999, you then left the bench in the bedside, and you went to work for McKenzie, why?
Dr. Andrew Allen (GRTS CEO) 5:59: Here, the truth is actually, I was going to go work for a biotech company that I’d started collaborating with when I was doing my PhD. And it was a company in Cambridge mass in the late 90s. And I was going to be their first translational physician working on some autoimmune stuff. But as often happens, the program I was going to work on blew up, for reasons, probably 10 years later, we started to understand, but at the time, we didn’t, and so the job opportunity literally evaporated. And for reasons that I actually don’t particularly remember now, I had a back pocket offer from McKinsey and a friend who’d gone there. And it seemed like a really interesting place to learn more about industry and biotech. And I decided that biotech was where I wanted to go. And this felt like a rational step in that direction, a little bit of a knight’s move, perhaps, but I have no regrets have so really enjoyed my time at McKinsey. And really, at that point, this was in around 2000, there was a huge explosion of interest from both biotech and pharma in oncology, which up to that point was a bit of a sort of pastime for me, and most companies, big companies didn’t really do oncology, it was too small. There are a few players AstraZeneca had their homeowners business, Bristol, of course, famously had Taxol on Platnumz. And event is as it was her tax tear. That was kind of it. But with the advent of sequencing, back in those days, it was things like expressed sequence tags as the basis for target discovery, if you remember all of that generating novel, monoclonal antibodies, this was clearly transformational for drug discovery. And because oncology has such a stark benefit risk with patients dying, the appetite to take risk is obviously much higher there than many other therapeutic areas. And so oncology became very important. And big pharma was new to this. And we turn to McKinsey, their trusted guides into this novel spaces to start asking questions of how should we think about entering oncology? Do we buy do we build, we partner, the classic sort of trio. So I spent a lot of time in oncology, and it was obviously a big move for me, and I’ve not really turned away from it in the subsequent 20 years, Fred, so
Neil Canavan (LifeSci Partners) 8:06: then after that, you moved on to the pharmaceutical companies in earnest, which would be Abbott Labs, and you took the job as global project head there, which sounds fairly important. Could you briefly describe your duties there? Like how large a team were you running? And were you then running oncology assets?
Dr. Andrew Allen (GRTS CEO) 8:22: Yeah, so actually joined up as a new product planning guy, which is a sort of commercial type role, because of my McKinsey experience, but I got the lucky break, when I joined one of my bosses there, the head of oncology development, obviously realized that I had this MD and PhD thing. And so what on earth are you doing commercial? Well, he sort of dragged me over into development. And I pointed out there was one small problem, which is I didn’t know anything about development. And he said, No, that’s fine, you can learn that. So I suddenly was parachuted into being this global lead for an international phase three Prostate Cancer Program, which had two large phase three trials running each about 1000 subjects. So it’s a fairly sizable team both obviously have operations and clinicians. And then in the classic Big Pharma matrix, functional retailers working with manufacturing, PK research, etc, etc. I really enjoyed that experience, the trial results were rather mixed, and unfortunately didn’t lead to approval of the product or the science was very interesting behind it. But obviously, I did learn a lot about both oncology, oncology development, and also, frankly, running teams, because up to that point, certainly within McKinsey was very small teams at timing, this was a different proposition. And it’s a whole different skill set management is non trivial. Most of us are not born with natural abilities, you generally have to learn them the hard way. So this was a great learning experience for me.
Neil Canavan (LifeSci Partners) 9:45: Tremendous. So you went on and then to use that experience, you went to a company that I’m quite familiar with do their work in HIV and HCV. And that’s Chiron, you spent two years there. 2004 2006. Now I mentioned this particular Isn’t obviously it was it’s part of your story. But second, it’s part of the genesis of gritstone as I understand it, and I always ask CEOs about situations that did not turn out as planned, they had to pivot and walk away. And for you that was Kira, and a program that had to do with a drug called publican. Now to preface your response to what I’m about to ask, I’d like to mention to listeners unfamiliar with the history of cancer immunotherapy, that the first immunotherapy drug to be approved with recombinant aisle two, and this in the hands of Steve Rosenberg, who was then and is now at the NIH, Rosenberg treated at for late stage cancer patients with aisle two, and almost all of them died, except a tiny handful two or three who were cured. Not a remission but cured. And this earned him a spot on the cover of Newsweek magazine in 1984. With a headline, magic bullet. So Andrew with that setup, tell me what happened to Kira? Yeah, it
Dr. Andrew Allen (GRTS CEO) 10:51: was very exciting. Next step. For me that was really important in what I’ve done subsequently. So I’d seen Steve Rosenberg on the horizon TV show in the UK in the early 80s, I guess. And I then got to meet him when I was at Chiron, which was pretty exciting. I was fairly starstruck. I mean, the guy I think, is just an extraordinary pioneer. And we’re all building on the phenomenal foundational work that he’s done over decades. I L to, as you say, had this extraordinary benefit risk profile, where everybody got very sick because of the capillary leak that was induced by high docile to, and most people derive really very limited or no therapeutic benefit. But the small group experienced truly miraculous cures. And it was interesting as we think about immunotherapy that throughout the 2000s, most people had really moved away from immunotherapy. And we’re very focused on targeted therapeutics, because we understood things like EGFR mutations created targets that were truly tumor specific, there was this huge drive to develop small molecule drugs or antibodies that can bind to those very specific targets, and lead to and profound benefit for patients. But there was a small group of folks, all of whom had worked with Steve Rosenberg, who’d seen that you could actually cure people of metastatic disease. I love targeted therapeutics, and obviously doing anything that’s helpful for patients with wonderful, but sadly, they’re really not hearing very many, if any patients, they’re buying time, which of course is valuable, but they’re not curing people. And if you’re 43 years old, with a young family, being told that we can keep you alive for another year, it’s better than not being alive for another year, but it’s not enough focus is woefully inadequate. And so I really have great respect for the a lot of them, you know, their names that Jedd wolchok. And Jeff, whoever’s in Patrick, who’s so one of the world who all of whom had gone through the Rosenberg system, they’d all seen the power of immunotherapy, and they were adhering to the path and trying to figure out a better way to deliver cancer immunotherapy. When I arrived to Chiron, we were marketing high decile to in kidney cancer and melanoma. And I was in charge of the Medical Affairs function, you’re trying to continue developing the product. And it was really hard because we just had limited tools, and really no good intellectual framework for how it was working. We knew it activated T cells, but what were their targets was such an important question. We just didn’t know Novartis came to buy Chiron and I have to say to my slight regret, I went upstate thereafter. And I turned away from immunotherapy. Much as I loved it, I felt it was too hard at that point. And that as I moved to my next company, find me and we were actively in licensing, but I just stayed away from all immunotherapy on the grounds that we didn’t understand it, there was no good animal model. And therefore chances are, you’re going to do a bunch of expensive human trials and it will then fail. So I turned away and focused on other much easier to understand areas of biology and more druggable targets as it were. But that was something I regretted and obviously, as we built gritstone, I was thrilled to kind of reengage with immunology, because we now actually understood something critical to developing novel immunotherapy. And so the story about if I can pivot to that is that as you know, in the 2010, sort of onward timeframe, the PD one antibodies started to and CTLA, four antibody Yervoy started to become clearly powerful immunotherapies that really shifted the benefit risk from high docile to little bit lots of risk to a much better value proposition A lot less risk and a lot more benefit. That was wonderful. But again, this the key question was how are these drugs working? Yes, we know they’re activating T cells, but again, what are these T cells? And most importantly, what are they recognizing? And Tim Chen Nyah Rizvi, Alexandria. Snyder had some seminal work published in the New England Journal, the very end of 2014. And then in science a few months later, where they showed that patients responding to these checkpoints were responding because it seemed the evidence initially was somewhat circumstantial, but the hypothesis was proposed that these responses were could be attributed to T cell recognition tumor Neo antigens. That go antigen is a mutant peptide derived from a mutated protein derived from mutant DNA that is found in tumors and is unique to tumors and creates an opportunity for the immune system to recognize something that is foreign. It’s not there when your immune system is developing as a fetus or neonate. So it’s nonself, as far as your immune system is concerned, and it’s unique to the tumor. And those are two properties that make it obviously make new antigens highly compelling as therapeutic targets. So Tim, and Naya, etc, publish these data. And everybody got very excited, because immediately there was a therapeutic hypothesis that if we could generate strong T cell responses to these Neo antigens, then we might be able to augment and extend the benefits of immunotherapy. And I emailed to Minaya soon as the paper came out. As I subsequently learned, Tim, just put it in the trash, Naya, however, remember it and so I asked him about it a week later, what did you think about that email from that strange guy in California? So they dug it up and emailed me back saying, come talk to us got nothing to lose? And then I sat down with them as you’ve published and discovered something. I think that’s really exciting. I think we should build a company here. And obviously they were excited to do that. They had all the science but didn’t have the company building experience. So we made a good team. And that was the genesis of gritstone in 2015.
Neil Canavan (LifeSci Partners) 16:25: Wow. Okay, so we’re gonna go straight to that. Just a second. I just want to mention Yes, on your path. Fermi on you did mention that. However, there’s another fairly big one you did also, which is you co founded a company called Clovis oncology, which is fairly well known for their PARP inhibitors. So I do want to throw that in there. But so you leave Clovis in 2015. The next six years, you’re involved in all sorts of things, first and foremost, the founding of gritstone. Now, the same year, you joined the board of cell design labs, you stayed with that for two years before they were acquired by Gilead. You also joined and remain to this day on the board of Sierra oncology. And in 2018, you joined the board of the MPM backed company TCRs squared. And finally, you retain a board membership in epizyme. That you join prior to leaving Clovis. Now, before we dive right into close technology and pipeline, just tell me, why do you want all of these, what seemed to me to be distractions?
Dr. Andrew Allen (GRTS CEO) 17:24: Yeah, I would definitely not refer to these as distractions. Obviously, my job is to build, grow and run a biotech company. This is a hard thing to do. Ask any buddy who sits in the seat. And at some point, you’re doing your first and you want to learn as much as you can about how to navigate the many challenges of running a biotech company, ranging from organizational growth, structure management, through to financing of course, recruiting the right board, frankly, working productively with your board, dealing with the bumps on the road that inevitably arise and how you particularly a public company, how you navigate that, in terms of the communication, managing through stock price fluctuations, dealing with stock market volatility, that’s often nothing to do with you, but you’re a victim of it. Nonetheless, these are all hard challenges. And my view has always been that the more I see of this in the more clever, experienced people I get to work with, the better I will be in my job. And so I’ve been privileged to join boards of good companies at different stages of development, and work with really good people on those boards. So if you look at the list of board members of those companies you’ve described, it’s an impressive cast of characters, and I’d be a fool if I didn’t think I could learn a huge amount from them. So I find these experiences to be invaluable for my job of running a company. They make me I think, I hope better at what I do than they would otherwise be.
Neil Canavan (LifeSci Partners) 18:51: Well, then I stand corrected, sir. Now I’m going to join the board. Okay. So gritstone, you have three programs that are named after stones being corals, slate and granite. And underpinning these structures is something called edge. So let’s first please describe for our listeners, what is edge here
Dr. Andrew Allen (GRTS CEO) 19:13: edge, I want to describe what it stands for it certain bunch of long words, but what it does is it helps us predict which bits of a protein can be recognized by T cells. So as I said earlier, T cell immunology is fundamentally different from antibodies. Antibodies are these famous Y shaped molecules that recognize bits of whole proteins. And they float around in the extracellular space, recognizing their targets and helping the immune system clear them up. And of course, most of us now have benefited from having antibodies to SARS cov to spike, and those antibodies if the virus enters our body, the antibodies will bind to it and neutralize it. So that’s antibodies are sort of quote easy in that regard. T cells serve a complimentary but very different function. They’re designed to recognize virally infected itself is where the virus has gone inside the cell, and is therefore invisible to antibodies. And our immune system developed this amazing property. And this is true of many higher species, that our cells constantly display fragments of all of the proteins from within the cell on the surface of the cell. And effectively, what they’re doing is they’re giving your immune system a little snapshot of what’s going on inside the cell. And these little protein fragments are displayed by platform molecules called HLA molecules, your tissue type. Now, 99.9% of the time, every cell is displaying fragments of normal cells, proteins on the surface, and your immune system is tolerized. To those so it just wanders ON by T cells wander through no notices given to these cells. But occasionally the cell will be virally infected. And on the surface of that cell will be a viral Fragment A peptide derived from a virus protein, and that is foreign nonself and highly immunogenic. And now your immune system will recognize it and kick into action. So that’s the key challenge for edge is how do we identify which bits of the target cell are going to be displayed and recognizable by your immune system.
Neil Canavan (LifeSci Partners) 21:13: Alright, so you put on the data, it comes out with prediction. And these predictions are then used to create vaccines BH for infectious disease or cancer. Now, let’s go as topical as we can you have a COVID program? Tell me about that.
Dr. Andrew Allen (GRTS CEO) 21:27: Yes. So when COVID-19 landed upon us at the beginning of 2020, there are some companies obviously jump straight on to developing a vaccine, you know, famously, Madorna biontech, and the team at Oxford that lined up with AstraZeneca. And Johnson and Johnson’s followed soon thereafter. And they all pursued the spike protein, because we’d learned quite a lot about Coronavirus from the original SARS epidemic in 2002. And then, obviously, MERS related in 2012. So we knew a fair bit about what to target from an antibiotic perspective. And so a lot of companies went to work on Spike, we obviously were not engineered at that point is a company to sort of drive aggressively against that in the same timeframe. But we sort of stepped back a little bit and said, Spike is a good target, but it’s not the only target. And there are probably other bits of the virus that might be very good targets for the T cell immune response, the killer T cells. So let’s give some thought to what would a next gen vaccine look like if you included spike to get the antibodies, but also other bits of the virus to drive a strong Killer T cell response? What would that vaccine look like? And that’s what we’ve basically built and we have a variety of constructs currently in human testing. Some of these are in collaboration with the NIH, some of them are in a program that’s aligned with Cepi, their coalition for epidemic preparedness innovation. And then some of these are in studies that we’re sponsoring ourselves as gritstone. So we’re doing some exploratory working humans looking at the best way to deliver these sort of expanded vaccines that contain more viral proteins. What’s the best way to present that to the human immune system? That’s the work we’re doing right now.
Neil Canavan (LifeSci Partners) 23:07: Okay, and I will mention that as of 9/24, you have dosed your first volunteer with a COVID-19 vaccine booster enhancer. And hopefully, we’ll be getting more news on that.
Dr. Andrew Allen (GRTS CEO) 23:18: yeah, because actually, that study in the UK is what’s referred to as a heterologous prime boost. So what we’re doing is we’re boosting with our RNA platform, people who’ve previously received the AstraZeneca adenovirus priming series. And that’s actually being discussed literally today, at the asef. Panel, the committee that’s reviewing the notion of should we be boosting the j&j patients with a different vaccine with the Maderna or biontech vaccine, so highly potent,
Neil Canavan (LifeSci Partners) 23:45: exciting, there will be. So let’s move on to the oncology assets. These are called slate and granite. Again, underpinning the antigen that you’re looking at is the edge predictive platform. I would first like to go to granite, granite is the personalized cancer vaccine platform, so and f1 for these patients. Now, before we talk about the data for this program, first tell me how are you leveraging circulating tumor DNA to figure out whether or not your vaccines are working?
Dr. Andrew Allen (GRTS CEO) 24:14: Yeah, immunotherapy is a new modality. And in clinical trials, we’re usually looking in early clinical trials in single arm studies, right? So you don’t have control groups, you’re just treating subjects with advanced cancer. So it’s important to remember, most of these phase one, two trials, when you begin are always in people who’ve exhausted all approved treatment options. So you’re treating patients who are in a really tough spot. And that’s a pretty hefty burden, I guess that we carry that these are patients who are desperate. We can all really sympathize with the position they’re in and we really want to help. Now from an immunotherapy point of view, these are kind of the toughest patients possible, because certainly with vaccines, you need time to mount an immune response. So these are not the patient where you’re most likely to have benefit, but that’s where you need to start. So we’ve been doing this work now for a couple of years, and we’re about to kind of move upstream. And in these patients, what you’re looking for is a signal that your drug is doing something useful. And traditionally, we’ve used shrinkage of tumors on a scan as the surrogate if you like for efficacy, because you don’t have time to do the big randomized studies and look at things that really matter, like survival. So you’re looking for the short term surrogate measures. And historically, with cancer, cytotoxic chemotherapy, like Platnumz and Taxanes and the targeted therapies, lesion shrinkage is a pretty good surrogate. And so it’s been used for approval. And that’s what investors in particular are very familiar with. What we’re doing is fundamentally different. What we’re doing is driving cells into lesions where they should meet their antigen and proliferate. And so it is not obvious that lesion shrinkage on radiology is going to be necessary for benefit to be ensuing. Right? Conceptually, you could imagine that the lesion that starts off as being full of tumor cells ends up being a blob, that’s entirely T cells, every five patients doing great, but the blob size hasn’t changed very much on a scale. So we didn’t know what would be true. So when we began the study, we said, great, well, we’ll obviously measure radiology, of course. But we’ll also measure some other parameters. And the one that’s now really growing rapidly in its value, is circulating tumor DNA. And it’s the simple notion that mutant DNA is found only in tumor cells, it is often leaked into the bloodstream, and you can measure it quantitatively. The more there is, the worse off you are. So if you treat and it goes up, that’s bad. If it goes down, that’s good. There’s more and more data suggesting that that simple math is actually pertinent. So it’s becoming a very important biomarker for early immunotherapy studies.
Neil Canavan (LifeSci Partners) 26:53: And the Holy Grail of good biomarker. So let’s go directly to the program. You have reported data on granite actually, just a month ago does smell briefly tell me what was the trial design? And what was the date of your report?
Dr. Andrew Allen (GRTS CEO) 27:06: Yeah, so this was a first in human phase one, two in these advanced patients, as I mentioned, it ended up mostly being colorectal cancer and gastric cancer and a couple of lung cancer patients, but mostly color, excellent gastric. And we did the dose escalation with the RNA, which was interesting, because we sort of took the simple mindset that more is good. Well, turns out with self amplifying RNA that actually more maybe less good. So we learned quite a lot there, for reasons we can go into. But low dose looks to be more effective and high dose when it comes to the RNA platform. And what we showed is that we were able to consistently induce T cells, killer T cells that recognize new antigens in patients who didn’t have them at the beginning. And that those cells could traffic into tumors, we’ve shown that and that then patients seem to derive benefit. Now we give our vaccines together with checkpoint inhibitors. And so the cleanest context is a tumor type where checkpoints really don’t do anything. And sadly, that is colorectal cancer. There’s the common circle, microsatellite, stable colorectal cancer. And in the third line, which is basically where we were treating patients, the outcomes are relentlessly depressing. Patients progress after two months, usually the very first scan, most patients have radiologic progression. And they die at six or seven months after initiation of therapy. And that is a highly consistent set of statistics. So we’re looking for something other than that, knowing that checkpoints alone don’t change those numbers. And so what we showed is that, in roughly half of our colorectal patients, were able to see evidence of molecular response, the CtDNA went down. And those patients remained free of disease progression and the live much longer than you would expect, a much longer than we saw in the patients who didn’t achieve molecular responses. This was not a randomized study. So let me be clear about that. And the numbers are small. But it was a very, very encouraging observation of value for this therapeutic in these tough patients who don’t respond to immunotherapy. So building on that, obviously, we’re now moving upstream. And we are launching our phase two, three program in the first line treatment of newly diagnosed metastatic colorectal cancer as maintenance therapy. So that’s a study that we’re just getting started now. And obviously, that some of the initial part is open label randomized so we’ll have phase two molecular response data in a randomized study in about 18 months time.
Neil Canavan (LifeSci Partners) 29:31: And now slate, this is the off the shelf shared neoantigen vaccine platform and their engines you’re looking at here we’re unfamiliar with p 53. And K RAS. Again, can you briefly describe this program and the antigens that you’re targeting?
Dr. Andrew Allen (GRTS CEO) 29:47: Yeah, so the granite program is, as you said, Enough, one we build the product for each patient and obviously that takes some time and carries some expense. But off the shelf product is highly attractive if such a thing can exist and We’ve been looking for shared Neo antigens. Well, as you say, k RAS is a very common mutation, and it’s presented by some common HLA types. And so we built an off the shelf, KRAS focused product, we had a few slots in the vaccine. So we put some p 53. Mutations in there as well. And this was our sort of version one vaccine, what we were able to show is that we actually did see molecular responses, particularly non small cell lung cancer, we had a recessed response in a patient who previously progressed on their checkpoint plus chemotherapy regimen. So we got very encouraging early signals, but the magnitude of the T cell response was a little disappointing compared to granite. And we dug deeply and realize that we probably had made a mistake by including p 53. And there’s a lot of p 53. On the surface of the tumor cells is the fragments of p 53. And it appears to be an immunodominant antigen, which means it crushes down the immune response to other antigens, perhaps including K RAS. And obviously, that was a problem because our patients basically had K RAS as their target lesion. P 53. was included as a maybe, but actually ended up probably being sabotage agent. So we redesign the product eliminated p 53, juiced up the KRAS presentation in various ways. And that’s just gone back into humans. And obviously, we’re going to be measuring those T cell responses and expecting to see better T cell responses, which should lead to better clinical responses. So building upon the molecular and research responses we’ve already seen, we’re hoping to see something quite impressive coming off of that sleep product. So it’s right in phase two now treating patients again with non small cell and colorectal cancer in next readout for that we should have meaningful data by middle of next year. So we
Neil Canavan (LifeSci Partners) 31:47: now I have a sounds like a science question, but it’s a marketing question, actually. So does HLA subtype matter when we’re looking at Slate?
Dr. Andrew Allen (GRTS CEO) 31:56: It does, yeah, it’s not enough, just have the Kaos mutation. In order for it to be a NEO antigen, you have to have the right HLA type to proceed to present the peptide on the cell surface. And so you need to identify the peptide plus its HLA pair. And then you’re looking for patients who have that combination. And it adds up to about 10 to 15% of non small cell, and 10 to 15% of colorectal cancer patients will have the relevant combinations. And that obviously, is a pretty sizable population of subjects.
Neil Canavan (LifeSci Partners) 32:26: Okay, I just have this a few more questions. But this one I’ve always wanted to ask. I hear a lot of companies present to me about Neo antigen platforms and their algorithm, which ultimately is just a lot of math in a black box. And so how do investors compare black boxes that you have on to it?
Dr. Andrew Allen (GRTS CEO) 32:42: I don’t think an investor can in truth, we are unusual in that we’ve actually published our data. And we’ve published our box, the code has been published in Nature, biotech. So if you are skilled in the art, you can actually replicate our model, and then you can compare yourself with it. But that obviously is really for the cognoscenti alone. In truth, no one is going to do that. I don’t think and what matters, of course, is clinical data, because it doesn’t really matter how good your predictions are, if your vaccine platform isn’t generating T cells that lead to therapeutic benefit. So at the end of the day, I think all we should be look looking at a clinical data, our patients benefiting, you know, show me the data, obviously, we’ve been focused on molecular responses we’ve discussed, and then put that into a randomized context. And let’s see how the product really delivers. And obviously, we’re excited to be in colorectal because it’s a second commonest killer, after lung cancer, huge numbers of patients, many of them young, the number of young patients with metastatic colorectal sadly, is increasing for reasons we don’t fully understand. Once you’re diagnosed with metastatic colorectal cancer, unfortunately, any form of therapy is basically palliative, ie you will succumb to that disease in a relatively short timeframe. We in survival now is pushing it two years, but it’s still way too short. If we’re able to extend the benefits of immunotherapy to a large number of colorectal cancer patients. That will be a very, very, very satisfying day and we’re on a good path right now.
Neil Canavan (LifeSci Partners) 34:06: All right, going to wrap up. I have three more questions. Two are strictly business related. Where is the IP for all of this?
Dr. Andrew Allen (GRTS CEO) 34:12: Yeah, this IP does reside with gritstone obviously built the Edge platform from scratch that lives with us. Some of the adenovirus work was already in public domain. It’s been around for a long time. But obviously the way we construct our vaccines obviously is proprietary and then we’re self amplifying RNA. Again, we’ve been building a lot of proprietary elements into the vaccine platform. It all resides with quits then we’ve been licensed very little in the form of IP.
Neil Canavan (LifeSci Partners) 34:36: Okay, and now money. According to your deck, you have 176.2 million in the bank as of June of this year, and you just landed a pipe in September for 55 million. What kind of runway does that give you?
Dr. Andrew Allen (GRTS CEO) 34:49: So we have runway now into mid 2023.
Neil Canavan (LifeSci Partners) 34:52: Splendid. And finally, most importantly, do people in your company really refer to themselves as Gritters?
Dr. Andrew Allen (GRTS CEO) 34:59: They do. There’s actually a constant competition to try and come up with better adjectives for members of the clan. Favorite is gritterati. But there’s gritter. Shanti. But there’s more to come, I’m sure.
Neil Canavan (LifeSci Partners) 35:13: All right. Well, there you have it. today. It’s been my pleasure to speak with Dr. Andrew Allen. He is the founder and CEO of gritstone. Dr. Thank you so much for joining me today.
Dr. Andrew Allen (GRTS CEO) 35:22: Thanks for having me.
Neil Canavan (LifeSci Partners) 35:25: Thank you for listening to this week’s benchtop bios. I hope that this episode will serve as yet another data point to guide you and your investment strategies. wish to hear more of life size benchtop files please subscribe to the podcast and iTunes Spotify or Google also if there’s a company or a particular executive like to get to know I do take requests and send those to and Canada at lifestyle advisors.com Until next week, then by that matter, good sell whatever boosts your perks