Gritstone bio, Inc.

Greetings. My name is LaTanya, 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 MacDougall, Head of Investor Relations and Corporate Communications at Gridstone. Please go ahead, sir.

Thank you, LaTanya, 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 from Gritstone are Andrew Allen, co-founder, president, and CEO, Ilya Economides, 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 10-Q with the U.S. 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. Bridgestone 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?

Thank you, George, and good afternoon, 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 Celia will present her 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 granite in frontline metastatic microsatellite stable colorectal cancer patients. These early data are highly encouraging, and they suggest that our personalized neoantigen 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 metastases, 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. And 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 metastases. 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 pseudoprogression with immunotherapy. Pseudoprogression 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 pseudoprogression in our Phase II study, which supports the use of PFS as a Phase III efficacy endpoint, perhaps as the basis for approval. And this topic will be discussed with FDA at our end of Phase II 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 I-II study of granite, wherein 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 I-II 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 I-II study of SLATE, our 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 benefits. Now, to limit the potential impact of pseudoprogression, 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 ctDNA. 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 ctDNA going into this study. What we observed is that chemo actually has an unexpectedly prolonged effect, rendering a single time point definition of ctDNA response, which is what we used, unreflective of clinical benefit. Now importantly, when we look at ctDNA trends across the entire study period, we see broad evidence that granite patients are indeed experiencing greater reductions in ctDNA versus those in the control group. This finding is consistent with the PFS signal. So the data emerging from the randomized Phase II of our GRANIT trial build upon what we observed in the Phase I-II trial and suggest that GRANIT neoantigen-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. But 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. Microsatellite 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 microsatellite-stable colorectal cancer. And since checkpoint inhibitor therapy alone has not delivered benefit in this setting. To date, to our knowledge, all of our neoantigen-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 as a 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 Granick, 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 a 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 KRAS-directed vaccine candidate in combination with an autologous mutant KRAS-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 neo-Antion targets we encode in granite, further underscores our leadership position in the field of neo-Antion 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 AI 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 ESCOMID conference reinforced previous phase one findings and highlighted the durability and potential broad utility of our self-amplifying mRNA vaccine against COVID-19. The efforts and dialogue with BARDA regarding running a phase 2B head-to-head study in COVID-19 continue, and we remain very excited about this important 10,000 subject study. Along with BARDA and others engaged in prophylaxis efforts, we've garnered 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 mRNA 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 positions.