GRTS H.C. Wainwright Healthcare Conference Transcript
Sean Lee (H.C. Analyst): Good morning everyone and thank you for joining the hc wainwright 23rd annual global investment conference. My name is Sean Lee and I’m an equity research analyst at the bank. Today’s fireside chat. I’d like to welcome Mr. Andrew Allen, the CEO of gritstone bio. gritstone is a clinical stage biotech company focused on the development of novel therapies for the treatment of cancer and infectious diseases. And it’s one of my top stock picks this year. So, to start us off, Andrew and for the benefit of investors who may not be familiar with gritstone, could you provide us with a quick background, the company and how you’re differentiating yourself in the fields of oncology, infectious diseases?
Andrew Allen (CEO): Certainly Well, first of all, thank you, Sean. Thanks for inviting us to participate in the conference, pleasure to be here. And gritstone is a company now around six years old. And we were birthed on the back of some very innovative observations made in the field of cancer immunotherapy. At the very end of 2014 and into 2015. When a team from Memorial Sloan Kettering observed that in solid tumor patients responding to checkpoint inhibitor therapy, the basis for that response appear to be the generation and activation of new antigen specific T cells, specifically CDA T cells. And it was that interesting observation that really led to the formation of gritstone. The therapeutic hypothesis was and remains that there are many solid tumor patients whose tumors do carry mutations that function as Neo antigens. But the patient’s adaptive immune system has failed to recognize those new antigens. And there is no T cell substrate for checkpoint inhibitors to work upon. And so for most patients for solid tumors, if you treat them with checkpoint inhibitors, you see very little in the way of efficacy that you can get autoimmune toxicity. And the hypothesis that by closing the gap, and by providing those patients with new anti reactive CDA T cells, will enable them to respond and benefit from checkpoint inhibitor therapy. So that was the basic idea that we started with. And over the last six years, we’ve built a platform to solve the two key problems inherent in that hypothesis. The first was, how do I identify from the many mutations in the tumor, which ones create true Neo antigens, and we developed a machine learning based approach trained on human tumor data to solve that problem. And secondly, once I’ve identified the Neo antigens, how do I administer those to humans to elicit a strong CDA T cell response, which is a hard thing to do. Most vaccines make good antibodies, good cd 40 cells that don’t prime CDA T cells. And so we worked on a vaccine platform that could generate primed CDA T cells. And interestingly, In so doing, we developed an ad no virus and a self amplifying RNA platform, both of which are now in phase two human trials. And we realized, of course, that these could have utility in other disease areas. And in the last 18 months or so, we’ve also become known for being an infectious disease company, because this pair of technologies actually lends itself extremely well to certain infectious diseases, where the goal is to generate strong antibody and CDA T cell responses. And our platform potentially can do that in a manner that most vaccines don’t. So over the last year, we’ve broadened from being an oncology company to being more of an immunotherapy company, and hence the name change earlier this year. So it’s been a busy six years, really developing this platform technology. And now we’re starting to see product candidates flowing off of the platform.
Sean Lee (H.C. Analyst): Thank you, Andrew, for that great overview. In my opinion, one of the most important clinical updates, milestones for the company this year is the upcoming data update from your leader, granite and slate programs at the expo Congress, which is held this month from the 16th to the 21st. So could you provide us with more details on what we can expect from this update? What are some of the key metrics that you believe investors will be most interested in?
Andrew Allen (CEO): Yes, so the data abstract is focused on our platform that is the personalized Neo ancient immunotherapy, we call that granite. So those are the data that will be in the mini oral presentation that will be given by Dr. Dan catenacci. On Friday, September 17. And a year ago, or just over a year ago, we presented very early data phase one data from the granite program. And what we’re doing here is we’re taking patients with solid tumors with a particular focus on gastric cancer, and most particularly colorectal cancer. And we’ve become quite focused on microsatellite stable colorectal cancer for a couple of reasons. Which I can go into. But that’s the place to really look for data. And it’s very instructive because with with that disease checkpoint inhibitors alone have really, essentially no efficacy, response rates are less than 1%. And medium progression free survival and overall survival appears to be really no different from what we see with the standard of care. And the third line, which is a rather disappointing median PFS of two months, the median overall survival of around six months. That’s what we’ve consistently seen. So when we use checkpoints together with our vaccines, you don’t need to worry about if you see anything interesting, is that related to the checkpoint? We kind of know the answer to that there’s unfortunately no. And therefore you have a fairly clean context to assess the activity of the vaccine platform we showed a year ago was that in the solid tumor patients who are coming to the end of the road there now they’ve completed standard of care and are now being treated with experimental therapy, we showed that we were able to consistently induce strong new action specific CDA T cell responses. And in one of the very first patients we treat in a colorectal cancer patient, we saw evidence of immune infiltration with lesions expanding a little bit acutely. And we saw it consistent with that a little spike in the CEA which is the classic solid tumor biomarker for for colon cancer carcinoembryonic antigen, we saw a little spike in CA, we saw a little spike in circulating tumor DNA as well, which is another very robust biomarker. And then by week 16, everything started to head south. Very interesting setup. That’s the only the data we had back then. So of course, what we now intend to show our long term follow up on that patient and multiple other patients who kind of look somewhat similar. So that’s the content of the esmo. presentation. It is longer term follow up on a meaningful number of site advanced solid tumor patients treated with are granted immunotherapy. And obviously, we’ll be reporting, of course, on safety and tolerability, where expectations obviously, I think, are quite comfortable that we shouldn’t see any major concerns there as as one would expect with a vaccine based immunotherapy. And on the immunogenicity side, we’ve already shown the strong consistent induction of CD eights. And in terms of efficacy. Most importantly, we’ll actually be looking to see how these patients are doing over a year out on therapy. Again, recognizing that particularly for colon cancer, the median overall survival for such patients is around six months. So of course, this is a single arm study. But nonetheless, we’ve got over 12 months of additional data on those subjects plus new subjects as well. So we’ll be looking at those data. We’ll be looking at the short term biomarkers, then of course, there’s radiology, but as I mentioned, circulating tumor DNA is becoming a more reliable biomarker for novel immunotherapy. Because radiology of course is just measuring the size of the lesion. And what we’re trying to do is drive T cells into lesions where they meet their antigen and proliferate. So simply measuring the size of a lesion doesn’t tell you much about what’s going on. Inside that region, where a circulating tumor DNA appears to be a much more informative real time biomarker. So we’ll be presenting a fair bit of data both on radiology and on the circulating tumor DNA biomarkers, as well as the long term survival data that I mentioned. So quite a fulsome update, I think it has no, and then the corporate event that will follow the the presentation during the academic session will also provide an update on slate, which is our off the shelf new entrant immunotherapy, which instead of being made for each patient just takes in particular k Ras mutations, which we know can be processed and presented as Neo antigens. And we have a product that elicits a strong Neo antigen response. And we’ll show clinical data from the version one of K Ras, although I’ve improved version two is just entered the clinic so very much more to come in that theme as well.
Sean Lee (H.C. Analyst): Okay, great. certainly looking forward to these data releases, especially on the circulating tumor DNA data. You mentioned. During your last quarterly update, you mentioned that the company plans to initiate two additional phase two granite studies later this year. Could you provide us with a little bit more color on these plans regarding the design of the studies? What are their expected timelines? What are the main goals you’re hoping to achieve with this studies? Do we expect these phase two studies to serve as blueprints for the larger pivotal studies further down the line?
Andrew Allen (CEO): Yeah, good questions. And I’m afraid I can’t answer much of those today. We’ll be disclosing that information on the Friday at the company event but As you correctly say, we have now announced that we will be launching two randomized controlled phase two trials in the setting of microsatellite stable colorectal cancer. So again, the data you’ll see on Friday, the 17th of September are in the very advanced disease setting. So this is basically third line or beyond. Meaning that these are patients who are presented with metastatic disease, and have all received typically the two chemo regimens that are now standard of care. And first is an oxaliplatin based regimen, and then an irinotecan based regimen. And those can be combined into you know, so individually, it’s full Foxx and full theory, they can be combined into folfox theory. And usually that’s given with Bevis ism AB. So anti veg f antibody maintenance as well. So those are the standard of care approaches. And the data you’ll see are where we’re taking patients typically in the third line. Whereas they said, unfortunately, the expectation for both the approved therapies and frankly, best supportive care is quite similar, which is a median PFS of around two months and a median survival of six, maybe seven months. That’s what the large data show us. Now, that’s where we obviously began the clinical program, of course, because this was a novel immunotherapy. But building off of what we’ve observed, we now intend to move upstream in the disease trajectory. And of course, there are benefits for an immunotherapy to move upstream. First of all, generally, the patients are fitter, their disease is progressing a little bit more slowly. And their immune responses generally are stronger. And all of this, of course, is good for an immunotherapy like ours, which is not the administration of an antibody or a T cell, we administer a vaccine. And so we need the patient’s adaptive immune system to respond. We need the patient to be healthy and have sufficient time for that team cell response to form to proliferate, to traffic and to then effect tumor killing. And that takes multiple weeks, Todd to have that opportunity in every patient if you’re treating an end of life. But as we move upstream, we have more time, and the patients are generally healthier. So it obviously makes sense for us to move up as all immunotherapies do. And we’ll be revealing the details of these two trials. One is still in the context of metastatic disease. One is in the context of Agilent disease. And we’ve thought a little bit about the Agilent opportunity. We all know that traditionally, adjuvant trials have been hard to run because many patients are cured by surgery. And so you run trials in the adjuvant space, not knowing who’s cured and who’s not cured. But knowing that actually because you’ve got a lot of cured patients in the population under study, these trials are inefficient. They’re slow, and they take a long time for events to accumulate until you achieve usually the event driven endpoint. The advent of circulating tumor DNA has transformed our ability to run trials management space, because now a patient who has definitive surgery for their localized disease. If they’re still circulating tumor DNA positive after surgery, then sadly, you know that patient has not been cured, and will do badly and will recur, using a standard endpoint of recurrence free survival. That is a patient population that desperately wants new and better therapies. And that’s a nice opportunity for a product like ours, to engage with a patient group that wants help, and where potentially you can run efficient trials. So we’re excited to disclose more specifics on those programs. And we’ll be doing that, as I say at the gritstone event later in the day on December on September 17.
Sean Lee (H.C. Analyst): Thank you, Andrew that was helpful. And I will certainly be watching the corporate event as well. Regarding slate, previously mentioned that the company is planning to introduce new versions of the cassette, the v2 and v3 into the phase one two study. So how are they different from the v1 version that you’ve deployed so far? And what are some of the advantages? What is the expected clinical development timeline for these new cassettes?
Andrew Allen (CEO): Yeah, great questions. So granite is, is an elegant product, but it’s made for each patient. And obviously, it would be nice to have an off the shelf product where you can just move in simply. And we can do that for certain common driver mutations, because we know that they are processed and presented as Neo antigens. And so that is true for most of the different carriers mutations that of course, are very common in solid tumors, carriers and P 53. Or two of the communists mutations that we find in solid tumors. And they’re a little bit different. Because k Ras, there are very few ways to constitutively activate that protein. And the mutations that activate k Ras are very much focused on code on 12. There, there are a couple of code on 13. And some are code on 61. And code on 12 is really where most of the action is. And everybody’s now familiar with the mutations that change the normal glycine at position 12, to some other amino acid. And so we’re all familiar with K, wrasse, g 12, C, G, 12, D, G, 12, V, G, 12. A, these all involve mutations at that code on 12. So because k Ras mutations are so common, and because there are so few mutations that actually activate the protein, that means you can actually have an off the shelf product that still is relevant to a fairly large population of patients. p 53 is very different p 53. It’s very common to lose p 53. function. But these are inactivating mutations. And there are lots of ways to destroy the function of a protein. And so while the to get technical, the phenotype of P 53 deficiency is very common, the individual genotypes are actually quite rare. So with our first version of slate, we were looking to build an off the shelf product relevant to solid tumor patients. And so we put all of these k Ras mutations into the cassette. And we put some p 53. mutations in as well, when it came to finding patients who were eligible. Nearly all of them were k Ras mutant eligible, because k Ras mutations plus the relevant HLA types are quite common pairs. But for p 53. Again, these specific individual mutations are actually quite rare in the population. And so very few patients came in who were relevant for that product. When we vaccinated subjects we observed was that the T cell response to these carriers mutations was actually a little bit underwhelming. We we were underwhelmed, because we had all the granite data showing what a great T cell response look like and what we could deliver with our vaccine platform. So remember, this is exactly the same vaccine platform, just different antigens. And we asked ourselves the question, why, why was it behaving so differently, and what we learned was that these p 53 mutations, while they were actually irrelevant, the vast majority of patients have strong what’s called immunodominance, meaning they’re really strong antigens to the immune system, and they crowd out the immune response to K Ras, which is a non dominant antigen. That obviously turned out to be a problem. Now, no one knew this, before we did the work, the hierarchy of antigens in human tumors was not known. But we’ve now demonstrated this phenomenon. And we’ve learned from it. So what we did was we redesigned this k Ras cassette, and we removed the P 53. mutations. And we’ve now put multiple copies of specific k Ras mutations into a single product that is now k Ras dedicated. And that’s what we call version two. All of the animal data suggests this will elicit a much stronger immune response. And that has gone back into humans the ind cleared just over a month ago. And the nice thing about these sleep products is they go straight into phase two, we know the dose, we know the schedule, we’ve got safety established, we don’t need to go back into dose escalation or dose modifications. So we’re straight into phase two. So the phase two data off of the version two should become available early next year, and certainly by the middle of next year. So it’s a quick timeline for the version two product. Now, this is all k Ras, but there are other Neo antigens that look very attractive. And we’ve put a third one a different one into what we call version three of slate. We’ve not disclosed the nature of that new engine yet. But that, again, is a different antigens in different patients. And it’s a product that’s centered on that single new antigen, very interesting product opportunity. And that will be going into the clinic next year. So we’ll be disclosing More on that in due course, and where these lead, others may follow. And they the field of new engine discovery remains vibrant. I think obviously, we’re leaders in that space, given our powerful technology, the new engine discovery, but in principle, there are many different sleep products that can be developed. And so this is, I think, a fast growing area. And we’re looking forward to showing the clinical data of the company event on the 17th which is new information. So watching the SEMA slate data update with version one, knowing the version two is coming, I think is a very interesting position to be in.
Sean Lee (H.C. Analyst): Thank you, Andrew, that makes it clearer. Okay, maybe switching track a little bit to the infectious diseases. Since the start of this year, the company has made a major push in this area. And one of your leading programs is the coral COVID-19 vaccine, which was developed in partnership with the National Institute of Allergy and Infectious diseases. Could you tell us how coral is different from all the already approved COVID vaccines that we have, and why do you think there still remains a commercial opportunity For this vaccine, where are you currently on the development timeline as well?
Andrew Allen (CEO): Okay, so we’re in phase one. And those data are being generated as we speak. And we’ll have some data at the end of the year. And then by mid next year, we’ll have a lot of data off of a series of different trials in different populations. We do have the niod collaboration. But we also recently announced a collaboration with Sepi the Coalition for epidemic preparedness innovations. And that is supporting a big trial in South Africa. In nearly 250 subjects receiving the self amplifying RNA program. We’re using COVID-19 antigens. So lots of data to come. We’re in the data harvesting mode as we speak, the basis for the program. And the reason we’ve pursued this, and the reason that third parties are interested in in partnering with us is that we all acknowledge the obvious the great success that’s been achieved with the first wave of vaccines in the mRNA. vaccines, in particular, have demonstrated remarkable efficacy and safety, which is obviously good news for all of us. But this spike specific, as we all know, right, they just contain the protein off of the surface of the viral particle called the spike protein. And they make very good antibody responses to spike. However, Spike can change. And of course, we’re seeing antigenic drift happening week to week, month to month with different variants, alpha, beta, gamma, etc. And of course, the worry is that that further variants will arise, which will have lower and lower sensitivity to the antibodies elicited by those first generation vaccines. And so how do we deal with that? Well, one option, of course, is to make another version of an RNA vaccine containing the new spike. And that I’m sure would work but takes time. And the question is, can we get broader immunity that was likely to provide coverage against these different variants in a way that’s perhaps a little bit more robust to the inevitable continued antigenic drift. And it’s hard to do that if you just focus on Spike, but it may be possible if you bring other viral components into your vaccine. And most of the other viral proteins which are highly conserved between the different family members lie in genes which are not found expressed as surface proteins, but they’re in proteins which are critical to viral function, but they live inside the virus and therefore antibodies will not recognize or find these targets. But instead, you’re relying now on T cell immunity. And so that you can now start to see how this connects into gritstone generating a strong T cell response particularly CDA T cells against other regions of the virus that are processed and presented as antigens on the surface of virally infected cells plays to the strengths of gritstone. And so recognizing this we started work early last year on a vaccine program that was obviously taking spike and generating and neutralizing antibodies to spike that clearly is a precon precondition, I think for an effective vaccine. But we’re adding to it additional elements of viral material in the form of fragments of viral genes that function as very good T cell antigens in the context of human cells, human HLA. And it’s this chi mirik. Cosette, as we’ve called it, where you’ve got the whole protein for antibodies and protein fragments for ch T cells. That’s the unique constellation that we’ve put together into our coral platform. And we can deliver those antigens either in the other viral vector system in the self amplifying RNA, or in both. And different trials have are looking at different constellations of vector and cassette. And because of course, you know, we can make a sequence of spike that uses the original sequence from the ancestral variant, we can use the beta variant, which is the South Africa variant, also known as B 1351. So you can play around with different spikes, you can play around with different bits of T cell epitopes. And we’ve got this whole program testing different elements of this constellation of components, which will start to read out by the end of this year and into early next year. So that by middle of next year, we should have a very good understanding of how you can drive a strong antibody and T cell response against SARS COVID. To that’s the point of differentiation of the program. Now maybe we’re not going to need it, maybe everything’s gone away by them, right. Unfortunately, doubt that’s the case. But this obviously leads into the notion of thinking about pan Corona, how do we generate this broader immunity? So there is a continued theme in our work all around, providing broad antigenic coverage through leveraging both surface proteins for antibodies and internal evolutionarily conserved protein. The function is T cell antigens. there’s a there’s a nice synergy between those two.
Sean Lee (H.C. Analyst): Certainly sounds very exciting. I’ll be looking forward to the data releases later this year. So in addition to curl, the company is also partnered with Gilead in the development of HIV vaccine. So what can you tell us about this program? And can we expect any updates over the next six to 12 months?
Andrew Allen (CEO): Well, this is Juliet’s program. So whether there’s an update is entirely in their gift. So I will not speak to that. We obviously were thrilled to sign this collaboration with Gilead, there is no better partner in the HIV space and Gilead. They liked obviously, the work that we’ve been doing on our different vaccine vectors, they kick the tires pretty extensively. So we did a lot of preclinical work. And obviously, they liked what they saw, and we signed the collaboration. So they they provide us with the antigens that they like, and this goes into our vectors. And so we then provide the vaccines and we manufacture the vaccines for then clinical testing. And so there should be an ind coming, as I say that will be on them to, to announce when that happens. But obviously, we’re excited by this platform. And it’s part of the kick and kill program that Gilead is running for attempted HIV cure, which is all about provoking latent viruses that are just silently living within cells, you want to provoke them into activity, which then means they start replicating, they put viral antigens on the surface of infected cells, that becomes the target that the immune system can lock on to. So kick and kill is the catchy phrase that they’ve been using. And we’re obviously excited to be a part of that platform.
Sean Lee (H.C. Analyst): Great. So finally, to help us close out, could you provide us with the highlight of the company’s financial situation? What’s your expected cash runway?
Andrew Allen (CEO): Yeah. So as of the end of the last quarter, we had $176.2 million of cash at hand, which sees us into early 2023. So we have well over a year’s runway, and looking forward to obviously just sharing the data catalysts that I’ve mentioned over the coming few months, as we continue to drive Chris them into the future.
Sean Lee (H.C. Analyst):Great. So thank you, Andrew, for joining me in this great fireside chat. Hopefully our next conference will be one way we can hold in person rather virtually. But in the meantime, we’re very grateful for your flexibility and your presence online this year. Thank you again from DC when writing.
Andrew Allen (CEO): My pleasure, thanks for inviting us again. Sean, look forward to seeing you in person soon.