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spk13: Greetings, my name is Latonya and welcome to Gridstone BIO's first quarter 2024 conference call. Please note this event is being recorded. At this time, I'd like to introduce George McDougal, head of investor relations and corporate communications at Gridstone. Please go ahead, sir.
spk06: Thank you, Latonya, and thank you everyone for joining Gridstone's conference call to discuss our financial results, clinical and business updates for the first quarter of 2024. With me on the call today are from Gridstone are Andrew Allen, co-founder, president and CEO, Celia Economedes, executive vice president and chief financial officer, and joining us for the Q&A portion will be Karen Youse, executive vice president and head of R&D. Today, after the market closed, we issued a press release providing corporate updates and financial results for the first quarter of 2024. The press release is available on our website. I'd like to remind you again that today's call is being webcast live and via a link on Gridstone's investor relations website where a replay will also be available after its completion. After our prepared remarks, we will open up the call for Q&A. During the course of this call, we will make forward looking statements that are based on current expectations. These forward looking statements are subject to a number of significant risks and uncertainties and actual results may differ materially from those that are described. We encourage you to review the risk factors in our most recent Form 10Q with the US Securities and Exchange Commission and is also available on our website. All statements on this call are made as of today based on information currently available to us, except as required by law, we disclaim any obligation to update such statements, even if our views change. Gridstone hosts these calls on an ad hoc basis and we hope you'll find today's call useful. With that, let me turn it over to Andrew. Andrew?
spk02: Thank you, George, and good afternoon,
spk09: everybody. And thank you for joining our first quarter of 2024 conference call. This is a very exciting time for Gridstone. And I'll begin today's call with a review of our most recent data from our personalized cancer vaccine program, GRANIT, as well as provide other clinical and corporate updates. Then Celie will present the financials and I'll come back to share closing remarks. Okay, let's get going. So, we recently shared preliminary data from our randomized phase two study of GRANIT in frontline metastatic microsatellite stable colorectal cancer patients. These early data are highly encouraging and they suggest that our personalized neoantibacterial vaccine is inducing therapeutically beneficial immune responses in the 67 patients included in our preliminary data set. Let's review what we showed. Firstly, the patients we're treating in this study are typical colorectal cancer patients. Approximately 75% of them have liver metastasis and approximately half of them have KRAS mutations. In terms of efficacy, we observed a trend towards progression free survival or PFS benefit with a hazard ratio in the overall population of 0.82. Median progression free survival or PFS in this indication is approximately 11 months. The last patient randomized in this study entered in August 2023. And these data were cut in early March 2024, meaning that last patient was on study for only approximately eight months, obviously short of the median PFS of 11 months. That renders these data rather immature, but even though these data are preliminary with over 60% censoring, meaning that over 60% of patients have not yet achieved an event of progression or death, this is a promising signal. As you may know, a hazard ratio of less than one implies a treatment benefit. The lower the hazard ratio, the stronger the treatment effect, i.e. the greater the benefit. Now to get a better understanding of what outcomes we may see as the overall data set matures, we identified at baseline prior to therapy a subset of patients that would be likely to progress faster than the overall population. Nearly all of these patients and we refer to them as high risk had liver metastasis. As expected, the PFS data in this group were more mature with 44% censoring. And the apparent PFS benefit associated with granite therapy was much stronger in this high risk population than in the overall population. We reported a hazard ratio of 0.52, which is striking and equates to a 48% relative risk reduction of progression or death with granite versus control. The early data in these high risk patients who give us information faster give us a potential window into the future. And as our data mature, meaning more patients experience disease progression, we expect the clinical benefits of granite versus standard of care to become more pronounced. We're excited to share the mature PFS data on all patients in the third quarter of 2024 and then we plan to discuss final phase three endpoints with the FDA. The encouraging PFS data at this early time point are important. PFS has historically been a proxy for overall survival in this disease and has therefore been used by regulatory authorities as the basis for approval of novel therapies. Previously, we've been cautious about PFS as an efficacy endpoint, given the potential for pseudo progression with immunotherapy. Pseudo progression is a phenomenon where lesions actually grow at the beginning of treatment prior to shrinking, which can lead to the attendant risk of patients being incorrectly labeled as having progressive disease. To date, we have seen no evidence of pseudo progression in our phase two study, which supports the use of PFS as a phase three efficacy endpoint, perhaps as the basis for approval. And this topic will be discussed with FDA at our end of phase two meeting. It's also worth noting we've seen apparent extension of PFS with granite before. We observed PFS and OS extension in third line colorectal cancer patients treated in our phase one two study of granite. Where in the 50% or so of patients with biochemical and molecular responses to granite, meaning reductions in tumor markers, we saw extended PFS and OS compared with the non responding patients. The interim data from this phase one two were published in nature medicine in 2022 and recall that we also saw similar signals of apparently extended OS again linked to biochemical and molecular responses in a phase one two study of slate off the shelf cancer vaccine that uses the same platform technologies as granite. But this was in patients with advanced non small cell and microsatellite stable colorectal cancer. The fact that we are seeing these concordant signals across different studies, different settings and different disease types gives us further confidence that granite could be driving meaningful clinical benefit. Now, to limit the potential impact of pseudo progression, we set PFS as the first secondary efficacy endpoint for our phase two trial and the primary endpoint was set as molecular response. A specific method of measuring change in circulating tumor DNA, which I'll abbreviate to CT DNA and this was based on what we'd seen in phase one two and of course there were no controls in that study. So therefore, we had to make an assumption about how chemotherapy would affect CT DNA going into this study. What we observed is that chemo actually has an unexpectedly prolonged effect rendering a single time point definition of CT DNA response, which is what we used unreflective of clinical benefit. Now, importantly, when we look at CT DNA trends across the entire study period, we see broad evidence that granite patients are indeed experiencing greater reductions in CT DNA versus those in the control group. This finding is consistent with the PFS signal. So the data emerging from the randomized phase two of our granite trial build upon what we observed in the phase one two trial. And suggest that granite neo angina directed immunotherapy could deliver a strong PFS result in metastatic colorectal cancer patients in a few months time. And again, we expect those mature data in the third quarter of this year. Why would positive data be significant for patients because colorectal cancer is now the leading and second leading cause of US cancer deaths in males and females under 50 respectively, in addition to being the second leading cause of cancer mortality worldwide. Micro satellite stable tumors comprise about 95% of all metastatic colorectal cancer diagnoses and treatment options are few with no approved immunotherapies for this highly resistant cold tumor. A positive randomized trial result would therefore offer desperately needed hope for one of the largest and most underserved solid tumor communities worldwide. Why would positive granite data be significant for the field because immunotherapy is generally believed to be ineffective in so called cold tumors such as micro satellite stable colorectal cancer and since checkpoint inhibitor therapy alone has not delivered benefit in this setting. To date to our knowledge, all of our neo angina directed personalized cancer vaccine competitors have studied cold metastatic tumors and have reported little to no signal of efficacy with their platforms. Hence their current focus on adjuvant indications and or hot tumors. Success for granite in a cold metastatic tumor could open the door for effective immunotherapy to the majority of solid tumor patients both in metastatic and adjuvant settings, a potentially dramatic expansion of the overall opportunity. And finally, why would positive mature PFS data be meaningful for gridstone because, of course, it suggests potential for a big opportunity immediately ahead of us in metastatic colorectal cancer. And that our objective of unlocking the broad set of immunologically cold tumors may be within reach. Having PFS reliable early measure of the effectiveness of our therapy gives us a potentially faster regulatory path in colorectal cancer and any other indications we pursue. Expanding the scope of immunotherapy to a wide spectrum of cancer patients is the holy grail of immuno oncology for good reason. It's challenging and it's not been done before despite decades of effort. Now, along with granite, we continue advancing our other promising programs and platform technologies and we're attracting great recognition and support. The recent slate publication in nature medicine highlights the promise of our off the shelf platform for solid tumors, which we believe is ready for plug and play applications across the spectrum of solid tumors. This promise is underscored by the ongoing collaboration with Dr. Steven Rosenberg of the National Cancer Institutes to evaluate our mutant Keras directed vaccine candidate in combination with an autologous mutant Keras directed TCRT cell therapy. The recent presentation of the latest improvements to edge our state of the art prediction platform that leverages artificial intelligence to identify the new ancient targets. We encode in granite. Further underscores our leadership position in the field of new engine directed cancer vaccines edge now predicts HLA class one presentation of epitopes with greater than 80% positive predictive value performance well beyond that of public models. And it offers what we believe to be a leading technology within the field edge also now includes a comprehensive state of the art model for predicting peptide presentation by HLA class two in the context of active vaccination. Which could serve to further strengthen T cell responses to our novel vaccines. We were among the first players to leverage technology in this fashion and will continue to invest in edge to further what we believe to be a key potential strategic advantage. Beyond oncology, we continue pushing forward in infectious disease, largely leveraging external dollars. Our recent presentation at the Eskimo conference, reinforced previous phase one findings and highlighted the durability and potential broad utility of our self amplifying vaccine against cobit 19. The efforts and dialogue with barter regarding running a face to be head to head study in cobit 19 continue and we remain very excited about this important 10,000 subject study. Along with barter and others engaged in prophylaxis efforts, we've gone to support from other leading players, including Gilead sciences for a therapeutic vaccine for HIV. And we remain excited about the broad potential applicability of our capabilities and self amplifying MRA platform in infectious disease. As our data mature across our portfolio, we continue to execute on our mission of delivering the most potent and durable vaccines. And now I'll turn over to Celia to speak to our financial position.
spk10: Thank you, Andrew. Good afternoon, everyone. We ended the quarter with cash, cash equivalents marketable securities and restricted cash of 52.8 million. As you are aware, in April of 2024, we completed an underwritten public offering resulting in gross proceeds to grit stone of 32.5 million. Bringing our pro forma cash, cash equivalents marketable securities and restricted cash to approximately 85.3 million. In February, we made the difficult decision to reduce our workforce by approximately 40%. Combined these actions have reduced our estimated quarterly cash burn rate and extended our runway into the fourth quarter of 2024. As you know, our priority is driving the granite program forward and our OPEX reflexes. On the infectious disease side to date, we have primarily funded our programs with non dilutive outside capital. Several of our long standing infectious disease collaborations continue and could potentially serve to bring additional capital to the company. As we think about the next steps for our I for our business, we are exploring strategic funding approaches to support our growing infectious disease programs and business. In addition to our current collaborations, new partnerships in both oncology and infectious disease could serve as additional sources of capital. Turning now to our Q1 2024 operating results. We reported a net loss of 40.4 million compared with 34 million for the same period last year. The increase in our net loss is primarily attributable to the decrease in collaboration revenue of 0.7 million, an increase in research and development expenses of 2.5 million and an increase in our expenses of 1.8 million. The establishment of collaborations and partnerships is a core part of our business strategy as we continue to leverage our unique platforms and capabilities. Our collaboration license and grant revenue for the first quarter ending March 31st 2024 totaled 1.7 million. This is compared to 2.4 million for the same period in 2023. Our research and development expenses were 33 million for the three months ended March 31st 2024 compared with 30.5 million for the same period in 2023. The increase in R&D costs is primarily due to a one-time severance and impairment charge and increases in facility related costs, which are partially offset by decreases in lab supplies, personnel related costs and outside services. GNA expenses for the period were 8.5 million, up from 6.7 million for the same period last year. The increase in GNA expenses for the period ending March 31st was primarily attributable to personnel related expenses, facilities related costs, outside services and a one-time severance charge. As of March 31st 2024, Gritstone had approximately 97.6 million shares of common stock outstanding, pre-funded warrants outstanding to purchase approximately 7.2 million shares of common stock at a nominal exercise price of one cent per share. And approximately 13.3 million shares of common stock at a nominal exercise price of one one hundredth of a cent per share. In summary, we are confident in our ability to execute on our strategic objectives and toward our growth inflection point. I'll now turn the call back over to Andrew for some closing remarks.
spk09: Thanks Celia. We started Gritstone to expand the emerging benefits of immunotherapy to all patients with solid tumors. And we're unwavering in our focus on that critical goal and very pleased with the progress we've made supporting the potential for new antigen based cancer vaccines.
spk17: Thank you. Thank you. You're back live. Okay, thank you. Thank you Celia.
spk09: We started Gritstone to expand the emerging benefits of immunotherapy to all patients with solid tumors. We are unwavering in our focus on that critical goal. Very pleased with the progress we've made supporting the potential for new antigen based cancer vaccines. Importantly, we're getting ever closer to randomized phase two data that we believe will demonstrate much needed benefit in a key population of newly diagnosed metastatic microsatellite stable colorectal cancer patients. This large group of patients is in desperate need of a therapeutic advance since median overall survival from the time of diagnosis has remained stuck at just around two years. We anticipate sharing mature PFS data as well as additional CT DNA data in the third quarter of this year. The preliminary PFS data we shared recently accompanied by the supportive CT DNA over time analysis demonstrating early trends in favor of granite immunotherapy are all very encouraging. And to remind you, these data are following on from and consistent with highly supportive phase one two data from a single arm trial in patients with very advanced metastatic disease. We're on the cusp of determinative data from this novel platform in a large patient population that has traditionally been considered unresponsive to immunotherapy. This is a truly exciting prospect for Gritstone, for the field, and most importantly for patients and their families. I'd like to thank you all for joining us today and I'll turn the call over to the operator for questions.
spk13: Thank you. We will now conduct a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in a question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Once again, that's star one at this time. One moment while we pose our first question. Our first question comes from Mark Fram with TD Cowan. Please proceed.
spk08: Thanks for taking my questions. Andrew, can you speak to how event rates in the CRC trial have evolved since the February update and given where they are now, how much uncertainty there still is or isn't that the mature PFS data will really be available in Q3?
spk02: Yeah,
spk09: it's a little early to give definitive answer because we don't obviously do exhaustive data cuts regularly that sites find that tiresome. But we have no reason to doubt the maturity of the data at this time point because a lot of phase three trials have been run in this very same population with highly consistent data. So the control arm, I strongly expect, will behave as many other control arms have before with that median PFS of around 11 months. As you're aware from the baseline disease and demographic data that we shared recently, this population of patients is very typical with 75% having liver metastasis. So there's no reason to believe that this is a particularly good or bad population of patients. There is, of course, some degree of informative censoring in the way we collect data, meaning that you get data on the patients who progress the fastest. And that is probably working against the granite arm because most people believe, with good reason, that vaccine immunotherapy is going to be more effective in people with lower volume, less extensive disease. Those patients will progress on average a bit more slowly. And of course, that means we have less data in that population, but we have more data in the high risk group that progress faster. And we showed you those data. And obviously that gave us further reason to be optimistic for mature data in Q3.
spk08: Okay, that's helpful. And then maybe on the bar to front, can you remind us how that money has actually been allocated in? And, you know, does it is required to be spent on cobit or is there some risk here that maybe with the avian flu epidemic going on, at least for now on the veterinary side that some of it may get moved over to flu and related to that. Any work you guys are doing on the avian flu side?
spk10: Yeah, so the specific contracts that we were awarded back in the fall of twenty, twenty, three was part of project next gen, which was focused on next generation. COVID vaccines, as you may recall, there were several periods for that contract and we were in the base period of which that time expired at the end of March and we are now in a no cost extension period of that contract while we work out. The gmp raw materials for launching the phase two B study. So those particular dollars in that particular contract was specific to cobit. Now, you may or may not recall that. Barta has actually shifted those funds into a different funding vehicle called our. So we have applied to that vehicle as well and are now waiting to hear back.
spk09: And then you'll we got your question on flu mark. The same principles apply to flu as applied to so every two, which is obviously the concern is always that there is ongoing mutation within those surface proteins, particularly the hemagglutinin and the neuraminidase that can lead to immune evasion. And that means, of course, you're often reacting to what is in the environment around you. The same principles that we deployed against stars could be too irrelevant here, i.e. that you want durable antibodies and ideally want to sell immunity against conserved regions of the virus. Because even if surface proteins are mutating, many of the other non structural proteins are not mutating because they're highly constrained. I either function is so critical to the virus that they can't change. That's the basic science that underpins our so called chimeric SARS coby two vaccine, where we include both the surface protein in the case of SARS coby two, of course, that spike. And we include regions of other non structural proteins that have conserved epitopes, particularly for CD8 T cells. You can apply that same logic to flu and we are doing preclinical work in influenza,
spk02: as you would imagine.
spk17: Okay, thank you.
spk14: Yep. The next question comes from John Miller
spk13: with Evercore. Please proceed.
spk12: Hi, this is John from John. Thanks for taking our question. I guess the first one is for the read out in the second half of the year. What is your bar for success? Do you need to see benefits from patients with low CD DNA baseline to feel confident moving forward?
spk02: Yeah, the median PFS
spk09: is 11 months. I think obviously we're looking for a meaningful improvement on that, which means it has a ratio probably better than point seven five. And certainly the data we've generated so far suggests we're on track to exceed that bar. Your question about low CT DNA. There are two populations really that have low CT DNA that we study. There's the group that begins the study with low CT DNA and that group generally would be called the lower risk group because we know and we've shown indeed a few weeks ago that if you have low CT DNA baseline, the rate of progression is lower than if you have high CT DNA. So that population is a lower risk population, although they all are expected to progress. So it's not that they have some kind of benign disease. They will progress and sadly that disease will kill nearly all of these patients in relatively short order, but they do progress a bit slower and perhaps vaccine based immunotherapy will be more effective in that population. There is generally a link between CT DNA level and disease burden. So it is reasonable to assert that the low CT DNA population population have lower disease burden, which is therefore perhaps more amenable to vaccine based immunotherapy. This is obviously the idea behind the focus on adjuvant indications that Moderna and BioNTech are pursuing. So it is an important population. Then there's a second group of low CT DNA, which is the patients who complete their induction chemotherapy and then are rendered CT DNA negative by that induction chemo. Now that's good for those patients. It obviously means they've done well on chemo. Sadly, most of them will recur, however, and that's an analysis that you may recall we presented a few weeks ago. And what we were able to show is that although the numbers are obviously quite small, there is a difference in the two arms whereby patients receiving vaccines stay negative for longer than the patients in the control arm. And there is more radiologic progressive disease in the control group than in the vaccine treated group. So those data are certainly encouraging and obviously will be following up in that population as well. So two different ways to answer your question, but both of them are important and both of them in principle could do even better on vaccine than the high risk group where we currently have the most mature data.
spk12: Thanks, Matt. Just want to follow up on the CT DNA. Okay, I guess why did CT DNA continue to decrease in the chemo arm after induction therapy? And do you have any thoughts on what sort of CT DNA endpoint might be more predictive for survival?
spk09: So we don't know. No one, we did not anticipate that, obviously. We wouldn't have set the endpoint the way we did. So clearly we had a failure of the endpoint in the study. That's an important distinction that I think has been lost on a lot of people. You can have an endpoint fail or a product fail or both. In this case, the endpoint failed because we saw CT DNA dropping in the control group just for the first three to four weeks after the completion of induction chemo. And so that's presumably telling us that there is some delayed or persistent effect of the induction chemotherapy. We had no data to guide us before we designed the study. So this is a new observation and obviously is one that tripped us up. But at some level, not that important because obviously what matters is that PFS is delivering clear signals here and is a more relevant regulatory endpoint, as we discussed in this call. And secondly, the long term CT DNA analysis is highly consistent with the PFS signal. In other words, patients on vaccine do better, CT DNA is controlled for longer. And that certainly is what you would expect from an active therapy in this disease setting. Now moving forward in this disease, we will not be worried about CT DNA because we now potentially entering phase three and we'll be using traditional endpoints. PFS or OS and obviously that's something we'll be discussing with the agency at the end of phase two meeting. And as you know, PFS has been used for approval in this first line disease setting. So that's what we'll be doing in metastatic colorectal cancer. However, we obviously if all goes well, we'll be developing the program in other settings. And particularly in earlier stage trials, especially if single arm CT DNA outcomes are potentially very important as an early efficacy metric before you get to big randomized studies. And therefore it is important that we understand how to interrogate CT DNA in a way that renders it a useful surrogate for clinical endpoints such as PFS and OS. Today, I can't give you the answer because we don't have the mature PFS and OS data. But of course, the data we're generating will be an invaluable resource to enable us to figure out a way to use CT DNA that adeptly captures long term clinical benefit and can then be deployed in single arm smaller trials in other indications.
spk12: Thank you so much.
spk02: Thank you.
spk13: The next question comes from Mayak Mantami with B Riley Securities. Please proceed.
spk03: Hey, guys, Madison here all for Mayak for taking our question. So, wondering what do you guys anticipate the touch points will be with the FDA whenever you meet to discuss it? So, we're going to look at the FDA's data for phase three and also curious how those patients could look relative to what we've seen in granite. If the 75% liver met 50% KRAS, if that's just kind of representative of the population. And then lastly, the fact we didn't see any pseudo-progression, do you expect that would hold in a phase three or is that something that you'll attempt to address in the design in the event there is pseudo-progressions? Appreciate it, guys. Thanks.
spk09: Yeah, thanks, Madison. Good question. So, in a slightly different order in which you asked the questions. By design, this was a very straightforward frontline study across the United States in a variety of centers with very straightforward inclusion and exclusion criteria, very standard. And that's good, of course, because it means there's not much opportunity for patient selection. You're just taking the patients that come through the door. And there aren't that many trials in frontline colorectal cancer. So, most people who were clinical trial eligible and at a site where our trial was operating would have been offered our study, which is why it enrolled very swiftly, particularly in the first half of 2023. So, there is unmet need there. The trial is very straightforward and recruits patients without any special selection. We don't anticipate changing that for phase three. Why would you want a representative population? So, that's good news. And obviously, we would anticipate that the degree of liver metastasis and KMS mutations will be constant in the phase three, because, of course, your dream is to run a phase three that is basically unchanged from your phase two. That reduces the chance that something new, you've made some new assumption or something else is happening that's altering the outcome. You want that so-called sleep easy phase three. So, our incentive is to change as little as possible. And obviously, we'll go to the FDA and the traditional forum is an end of phase two meeting, which we'd anticipate towards the end of this year, taking to them the data from the study, which, of course, we'll have in hand in Q3. And then we'll be discussing, among other things, the phase three primary efficacy endpoint. And that is likely to be a choice between PFS and OS. We also, of course, need to align with the FDA on manufacturing, because these are complex products. We've obviously been in lockstep with the FDA from the very get go. In fact, we first spoke to the FDA about manufacturing before we were in the clinic when we were literally designing the layout of our bio manufacturing facility. So we held a type C meeting back then just to solicit FDA's input to make sure that we were on the right track in terms of the way we make these products. There's obviously a step up in regulatory quality as you move to phase three commercial, and we need to make sure that we're aligned with the agency. That's also part of the end of phase two meeting alongside the clinical endpoint discussions.
spk17: Got it. Thank you.
spk14: The next question comes from Kaveri Pullman with BTIG.
spk13: Please proceed.
spk07: Hi, this is Christian. I'm on for Kaveri today. My first question is, I would like an update on the CORAL program. I saw that you guys presented positive data recently on the CORAL study in South African patients. And there was positive data in the three vaccine candidates. So is there any development theory? Are you guys planning to, which candidate are you guys planning to move forward?
spk09: Obviously, if successful with our BARDA study, we'll be moving forward another candidate because, of course, we're expecting there to be an update of the strain that is required for the fall season of 2024. As you're aware, WHO and the EU have issued guidance to use the JN1 variant. If you remember, obviously, last year, it was the XBB 1.5 variant. So there will be a strain change. We've not disclosed the exact nature of the T cell component that we'll include in the vaccine, but that will be included. That's part of our chimeric vaccine design intended to induce protective antibodies as well as those protective T cell responses against conserved antigens. So that's the expectation going forward. And that's the primary focus of the CORAL program right now.
spk07: Okay, thank you. And regarding the BARDA study, I just noticed in the press release that the company will be initiating that as soon as they can. Should we still expect that in fall 2024 or is that being reevaluated?
spk09: Yeah, it depends a little on our ability to meet the FDA's criteria around GMP raw materials. So obviously that's a little contingent on further interactions with the agency, which is why we are cautious about specific guidance at this
spk02: point.
spk07: Okay, thank you so much.
spk02: Thank
spk13: you. The next question comes from Catherine Novak with Jones Trading. Please proceed.
spk11: Oh, hi guys. Good afternoon. Thanks for taking the questions. Just a couple, I guess. I wanted to ask about the prevalence of high risk disease versus low risk. And, you know, do you consider this a predictive enrichment factor or mainly saw benefit due to the fact that patients had more mature PFS curves?
spk09: Yeah, thanks Catherine. So the way we did this analysis was to look at the, we calculated the baseline circulating tumor DNA on every subject where we had that information. And then we took the control group and we split it right down the middle. And we just bifurcated that population. We then applied that same cutoff to the vaccine arm, the test arm. And it actually was slightly lower than the median for the vaccine arm. So the vaccine patients actually had slightly higher baseline CT DNA than the control arm, which obviously works against the vaccine arm, all things being equal, which is good from a conservative data analysis point of view. So that's how we set it. So it was a 50 50 in the control arm, slightly more in the vaccine arm. The, the reason we did that was simply to try and generate a more mature data set, because of course everybody is asking the question, ourselves included. What will these data look like when we have the mature data? And so what we were trying to do was find a very fair way of identifying a population of patients who have events faster. And baseline CT DNA is remarkably efficient at selecting for the patients who have faster events. And that's clear from the Kaplan-Meier curves that we showed. So that's why we did it. And you could argue reasonably that the high risk population is the population that's going to do the worst on vaccine. Because, as I mentioned in my response to another question, there is a general belief based now on data, but lower volume disease does better on immunotherapy and perhaps particularly on vaccine immunotherapy. The lowest volume disease is in the adjuvant setting. And that's where, of course, we've seen particular success by Moderna, who obviously did not see signal in advanced metastatic disease, but have seen signal in high risk adjuvant melanoma. So within a metastatic colorectal population, there are obviously some patients with very extensive disease and some patients with very mild or minor disease, but they all have metastatic colorectal cancer. CT DNA splits them and it gives you more data faster in that high risk group with more extensive disease. So the fact we saw such a strong signal there is reassuring that as the data mature, we will then see a signal at least as strong in the low risk group, maybe stronger. And therefore, our intention is not to think about this high risk stratification once we're past Q3. And at that point, we anticipate we'll be including everybody and treating everybody and hopefully seeking a label in everybody. Because in principle, if the product works in everybody, which is what we anticipate, then, of course, you don't want to be selecting out against particular patients.
spk11: Got it. Thank you. That's very helpful.
spk13: Yep. The next question comes from Roy Buckman with Citizens JMP. Please
spk05: proceed. Hey, thanks for taking the questions. I think you just answered my granite question, which is stratifying by CT DNA. So it sounds like you're not going to do that going forward into the phase three.
spk09: Well, let's be clear, Roy. We haven't got the data yet in the low risk group. So everything we're saying today is speculation. What we have got is data in the high risk group, which looks very good. Now we wait for data in the low risk group. So I want to be super clear about this. It's not that we have no signal in the low risk group. We have no data in the low risk group because very few of them as of early March had achieved a progression or death event. So it's not evidence of absence of effect. It's absence of any evidence about anything. And therefore you just wait. But what you would expect based on the literature and what we've seen from others is that the effect of the vaccine in that low risk group will be at least as good. As in the high risk group, perhaps better. And if that's indeed what we see, then there would be no reason to worry about patient selection going forward.
spk05: Okay, got it. Okay. Thank you. I guess a few on coral. So this is our PV holding vehicle or whatever it is, and you're waiting to hear back from that. I guess any sense on when you might hear back on that and is that a is that a new set of people that are going to decide whether they like this program or that program or technology versus the first decision on the grant?
spk02: It is a different entity,
spk09: but obviously there is relatedness. But the exact nature of those relationships is not very apparent to outsiders like us. So related, but distinct.
spk10: It is a consortium that's under it's a consortium that's under barter's direction.
spk05: Do you have any timelines of when when they're going to get back to you?
spk10: We have not provided any guidance on that.
spk05: Okay. And then you mentioned potentially partnering to fund the ID programs. Was that also potentially include coven 19?
spk17: Thanks. Yes, potentially. Okay. Thank you. Thanks.
spk14: The next question comes from author with H. C. Rainwright.
spk13: Please proceed.
spk15: Hey, good afternoon, Andrew and team. These are on
spk16: for a shot. I just had a quick one regarding the granite. Just curious when you see the CDD in the reduction post to the chemo. Did you see, is there any correlation for the reduction with the baseline character of the tumor? I just curious, is there any any way to you guys to minimize these noisy background for when you if you go going to use the CD, CD, CT DNA to further as a biomark to for the evaluation in the future?
spk09: We haven't performed those analysis yet. Obviously, it's a phenomenon that relates to the tumor response to chemotherapy, specifically to full Fox or full Fox area plus better system app. And that regimen is only used in colorectal cancer derivatives of it, I guess, used in pancreatic cancer, but it wouldn't have great utility outside of this colorectal cancer setting. And so determining who does well on chemotherapy is obviously not particularly critical to our development program going forward.
spk16: Thanks. And my second question for the for the updated read for the read out in the third quarter. Besides the PFS mature PFS and more CT DNA data, what other data could we expect to can give us more information regarding the pivotal study design?
spk09: Yeah, so the overall survival data will still be very immature at that point. Median survival, survival is around two years in this disease. So, again, following the same logic, if PFS is basically around one year or just shy, you need to give it another year to get to very mature data. Now we are doing some additional analysis. Karen, our head of R&D is on the on the phone here. So, Karen, perhaps you want to give a little flavor as to what additional correlates we might have for the Q3 update.
spk01: Yeah, we we are looking in a subset of the patient population. We perform TCR-seq. We perform ELISBOT analysis. So we do look at translational data, which we actually have published significant data on in our nature medicine papers. So we do some of that work, but we don't anticipate the data to look any different. So I'll go for manuscript, but TCR-seq and ELISBOT, you can anticipate that. We are also potentially, if we have enough cells, perform ICS looking for poly functionality or even killing. So we have a great toolbox and depending on the number of cells we have from these plot draws, we will in a subset only of these patients looking for T cell response TCR-seq as well as functionality of the T cells.
spk15: Great. Thanks for the additional color. Thanks for taking my question. Thank you.
spk13: The next question comes from Kareen Johnson with Goldman Sachs. Please proceed.
spk04: Hi, this is Omari Owen for Kareen. I have a couple of questions. What gives you confidence that the PFS will strengthen if the data matures and on the hazard ratio is the piecewise Cox pH model of pre-specified analysis?
spk02: So the confidence comes
spk09: from two primary sources directly and one indirect source. First of all, we saw the same phenomenon of PFS and OS extension in the Phase 1-2 study in third line colorectal cancer patients. Not a randomized study, but those who had reductions in their biomarkers, including CT DNA, had this apparently extended PFS and OS. So we're repeating that observation in this study. Secondly, the high risk analysis gives you a way of peering into the future. And it's obviously not a perfect analysis. No one can foretell the future. If they could, it would obviously be easy. But it's a reasonable way of asking the question. If I expect the low risk group to behave similar to the high risk group, then what would I see in the future? And obviously the high risk analysis is quite mature and looks very encouraging. So that's the second direct bit of evidence to encourage optimism for the Q3 mature data. The indirect support comes from the notion that the data we're waiting for are in the low risk patients and data from other players, most notably Moderna, suggests that those low volume disease patients are the ones that do best on vaccine based immunotherapy. Therefore, if you believe that that applies to this study, we should see signals at least as strong, if not stronger in the lower risk population as the data set rounds out and matures. Your second question was about the GPW statistical test, and I couldn't quite catch it. Was the question, are we using that in the summer?
spk04: The piecewise Cox pH model with a pre-specified analysis for this study.
spk09: Yes, yes. So we we've actually been in a lengthy dialogue with FDA around the way to statistically analyze the study, because it is clear that patients are randomized at the beginning of their induction chemotherapy. And for the first on average five months, the treatments are identical across the two arms of the study, and then the treatments diverge. And therefore, the Kaplan-Meier plots of progression free survival will not meet the proportional hazards assumption. And that is a requirement if you're going to use the standard log rank test. So we knew that the way the study was designed, log rank was not the appropriate statistical tests and the appropriate way to analyze these curves. In fact, what you wanted to do was a time weighted system. So we entered this discussion with the agency and we settled with them on GPW, the global, sorry, generalized piecewise analysis. And we've done a very simple model for this study. Any progression event prior to six months is given a weighting of zero and any progression event after six months is given a weighting of one. That's the way we've analyzed these data. And that was pre-specified.
spk17: Yes. Thank you.
spk14: Thank you. Thank you.
spk13: At this time, there are no further questions in queue. I'd like to turn the call back to Andrew Allen for closing comments.
spk09: Thank you very much. That represents the end of our call. So we have nothing further to add. Just like to thank you for your time and attention. Obviously, we're very excited to see these data in Q3. And we hope to be able to really move the ball forward for these patients who've been waiting a long time for some reasons for optimism. And with that, thank you very much.
spk13: Thank you. This does conclude today's teleconference. You may disconnect your line to this time. Thank you for your participation and have a great day.
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