Gritstone bio, Inc.

My name is Erica, and welcome to Gritstone's BIO First Quarter 2023 Earnings Conference Call. Please note this event is being recorded. At this time, I'd like to introduce George McDougall, Director, Investor Relations, and Corporate Communications at Gritstone. Please go ahead, sir.

Thank you, Erica, and thank you, everyone, for joining us for Gritstone BIO's conference call to discuss our financial results clinical, and business updates for the first quarter of 2023. With me on the call today from Gritstone Bio are Andrew Allen, co-founder, president, and CEO, and Celia Economides, executive vice president and chief financial officer. Today, after the market closed, we issued a press release providing our first quarter 2023 financial results, as well as clinical and business updates. The press release is available on our website. I'd like to remind you that today's call is being webcast live via a link on Gridstone's Investor Relations website, where a replay will 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 our actual results may differ materially from those described. We encourage you to review the risk factors in our most recent Form 10-K filed with the U.S. Securities and Exchange Commission and 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. With that, let me turn the call over to Andrew. Andrew?

Thanks, George, and good afternoon, everybody. Thanks for joining us for our first quarter 2023 conference call. This is a really exciting time for Gridstone. Significant momentum has been established for our personalized cancer vaccine or PCV program called Granit, which is driving towards randomized clinical trial data. And with infectious disease, we're making great strides in realizing the untapped potential of self-amplifying mRNA. I'll begin today's call with a review of recent clinical and corporate developments, including the expansion of the GRANIT study we announced today. Celia will then present her financials, and I'll come back to share closing remarks. Okay, let's dive right in. So most important to share with you today is the update regarding GRANIT, which is currently in phase two part of a phase two three study in patients with newly diagnosed metastatic microsatellite stable colorectal cancer. I'll refer to this as MSS-CRC. This morning, we shared an enrollment update from the study. And I'm delighted to tell you that we're enrolling at a rapid pace and very close to achieving our initial target enrollment of 80 patients. We also announced that we've made the strategic decision to expand the Phase 2 portion of the Phase 2-3 study to 100 total patients. And in order to do this, we'll be shifting near-term funds from our off-the-shelf neoantion program, SLATE. SLATE is a key part of the future, but our planned randomized trial is not expected to deliver data near term, of course, and thus must play second fiddle to granite as we maximize the potential of this high-value PCV opportunity. Now, over the years, you've heard me speak of our strong belief that our PCV approach could be uniquely capable of unlocking the power of immunotherapy for patients with immunologically cold tumors. Our Phase I-II data from Granit in advanced cancer patients that included immunologically cold tumors published in Nature Medicine last summer provided strong clinical data in support of the therapeutic hypothesis. Moderna's recent positive Phase IIb data, presented at AACR in April, provided further evidence supporting the PCV approach. In Moderna's case, in the immunologically hot context, of adjuvant melanoma. And then just yesterday in Nature, Vinod Balachandran and his team from Memorial Sloan Kettering published data in the adjuvant therapy of pancreatic ductal adenocarcinoma with some provocative immunology and clinical data, potentially further supporting PCV, this time in the cold context of pancreatic cancer. Our current GRANIT trial is how this all comes together. with our Phase II study potentially being the first to deliver randomized data supporting a neoantigen-based PCV against MSS-CRC. And I think it's widely recognized that if granite delivers benefit in metastatic MSS-CRC and notoriously cold tumor that is difficult to treat with immunotherapy, the opportunity for further application is enormous and potentially encompasses all solid tumors, both hot and cold. Now there are several reasons why we elected to expand the Phase II study. Let me detail them. Firstly, a larger number of patients will provide a better estimate of treatment effect size, which will in turn inform an optimal Phase III study sample size. So to drill down on that point, the current study is designed as a Phase II-III. And to remind you, the primary efficacy endpoint for the Phase II component is molecular response. or ctDNA response, with secondary endpoints including progression-free survival, or PFS, and overall survival, or OS. Now, we anticipate discussing the phase two data with regulatory authorities in the first half of 2024, and then moving into phase three. The phase three primary efficacy endpoint is to be determined based on our interaction with regulators, but it is likely to be a traditional endpoint, such as PFS or OS. Powering the phase three study for a time to event endpoint will be done using observed phase two data, since the phase two and three components are statistically separate. The greater the precision of the estimate of treatment effect size from phase two data, the easier it is to power phase three appropriately. Secondly, momentum behind study enrollment has been very strong. As of May the 10th, 2023, we've randomized 71 of the initially planned 80 patients, and that number's already gone up, and approximately half of these were randomized in 2023. All sites are screening and consenting enthusiastically, and we expect this strong enrollment trend to continue for the foreseeable future. We anticipate completing enrollment of the full 100 subjects in the third quarter of 2023. Now, sadly, and worth reflecting on, this momentum arises in part from the high unmet clinical need. Colorectal cancer is the second leading cause of cancer death in the United States, and over 150,000 people are expected to be diagnosed with CRC this year alone. Median survival for patients with metastatic disease is around two years. Better therapeutics are desperately needed. Innovation is needed, and we aim to deliver both. Thirdly, granite is the tip of the spear for our neoantigen programs. The basic idea is that delivering many neoantigens to solid tumor patients in a potent vaccine that drives strong CD8 T cell responses will drive clinical benefit. Now, granite seeks to do exactly that, leveraging our neural network epitope identification platform, Edge, to accurately predict which subset of tumor DNA mutations forms true neoantigens that will stimulate an effective anti-tumor immune response. And our published clinical data show that patients mount strong T cell responses to most of the administered neoantigens, with T cells trafficking into their tumors and killing tumor cells, as evidenced by the approximately 50% molecular response rate that we've observed. And as you are well aware, our data further show that those patients with molecular responses experience extended overall survival versus those without. However, a PCV approach will always take more time and cost than an off-the-shelf approach. We're rapidly building out our off-the-shelf program, SLATE, which delivers shared tumor-specific antigens to each patient, but it is temporarily behind Granit in development. It takes work and time to identify high-quality shared tumor-specific antigens that can be combined into a single vaccine that delivers multiple relevant antigens to each patient. So where Granit leads, Slate will likely follow. However, showing that Granit delivers efficacy in a randomized controlled trial is our highest near-term priority. Now, before we move on from Granit and oncology, I'd like to draw your attention to the value of circulating tumor DNA, or ctDNA, as an efficacy biomarker. Reduction in ctDNA, referred to as a molecular response, is rapidly emerging as a likely superior surrogate biomarker of efficacy over radiology in the early assessment of solid tumor immunotherapy. It makes particular sense for us at Gridstone to assess molecular response in our studies because we aim to drive T cells into tumor lesions, where we have shown that they can meet cognate, antigen, and proliferate. potentially making the lesions appear bigger. This obviously makes radiology-based tools susceptible to errors of mislabeling. Lesions that increase or remain stable in size are labeled as progressive disease or stable disease, respectively, when, in fact, the patient's immune system may be newly at war with their tumor, i.e., anything but stable. ctDNA dynamics are casting light on the key issue of what's actually going on in those complex lesions. Tumor cell destruction is reflected by a decrease in ctDNA over time. Now molecular response is defined as a 30% reduction in ctDNA as the primary endpoint for the Phase II portion of our GRANIT study. We originally powered the study for this endpoint, and we've waited for mature clinical data from our Phase I-II study in advanced cancer patients to allow us to carefully define molecular response in a data-driven manner that is expected to best predict overall survival in colorectal cancer. Now, to remind you, no one's done this before, so we've had to build the framework ourselves. No one's ever generated strong de novo neoantion-specific T cell responses in cold tumor patients before. No one's combined this with checkpoint inhibition. So there is no off-the-shelf answer to the question, what's the best surrogate endpoint for overall survival? We've had to find the answer, and that's exactly what we've done. We've generated data in phase one, two, and we're now deploying a data-driven definition to establish efficacy in a randomized controlled phase two trial. Once efficacy has been demonstrated in phase two, we'll proceed into a pivotal phase three. And as I've already noted, We anticipate using a traditional efficacy endpoint such as PFS or OS in the pivotal trial, but there is a possibility that molecular response will have accrued enough support by 2024 to be used as a surrogate endpoint for accelerated approval. We would like that, but we are not dependent on it. We're very excited by the Granite Phase 2 trial, the momentum it's gained, and its potential to serve as a major advance in cancer immunotherapy as we seek to extend the emerging benefits of PCV to cold tumors. We will update you further on enrollment once complete, and we look forward to sharing preliminary data in the first quarter of 2024. Now let's move over to infectious disease, where data demonstrating potential advantages of self-amplifying mRNA or SAM RNA over first-generation mRNA vaccines continue to flow from our clinical stage CORAL program, centered on SARS-CoV-2. And the differentiation of SAM RNA from mRNA is now becoming clearer. The prolonged antigen expression associated with SAM RNA vaccines appears to be translating into a more durable neutralizing antibody response, potentially reducing the need for frequent booster vaccinations. And the replication of the RNA once in the cell appears to enable similar immunogenicity as non-amplifying mRNA at a fraction of the dose, offering a cost of goods benefit. In April of this year, we presented new six-month neutralizing antibody data from our ongoing Phase I Coral Boost and Coral CEPI studies at the 33rd European Congress of Clinical Microbiology and Infectious Diseases, also known as ECMID. These presentations in Copenhagen demonstrated that the robust neutralizing antibody responses driven by our SAM RNA vaccine candidates persist for at least six months, regardless of setting and across multiple subject populations. Of note in the Coral CEPI presentation, we reported high neutralizing antibody levels and persistence at six months in over 100 vaccine-naive subjects, a meaningful increase in subject numbers versus our prior data reports. SAM RNA is rapidly emerging as a tolerable, immunogenic, and flexible next-generation platform for vaccines against infectious diseases, including COVID-19. And the induction of broad, long-term, and potentially variant-proof immune responses that we're seeing in our phase one studies is highly promising for the field. We look forward to continuing to work with collaborators to demonstrate the full potential of our SAM RNA platform against both SARS-CoV-2 and other important viruses. We expect to share additional data from our coral program this fall, and these data will relate to different immunogen designs, illustrating the flexibility of the platform to accommodate both B-cell and T-cell epitopes in efficient formats. It is clear that there is still need for next-generation solutions against COVID-19, and the recent actions by the White House and BARDA are encouraging signals that the pursuit of enhanced breadth and durability of protection is not going to the wayside. Outside of our PCV and SARS-CoV-2 programs, our forward-looking efforts to identify and develop potentially transformative vaccines continues. Our partnership with Gilead to develop a vaccine-based curative immunotherapy treatment for HIV remains active and ongoing in a phase one study. Promising results from a preclinical study in non-human primates within this program were presented at the Conference on Retroviruses and Opportunistic Infections in January. And our preclinical projects against human papillomavirus, influenza, and a new combination vaccine against multiple respiratory viruses continue to progress well. I'll now turn it over to Celia, who will provide more color on our financial results for the first quarter of 2023. Celia?