Gritstone bio, Inc.

Greetings. My name is Joe, and I'll be your conference operator today. Welcome to Gridstone BIO's fourth quarter and full year 2022 results 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 Gridstone. Please go ahead, sir.

Thank you, operator, and thank you, everyone, for joining us for Gridstone BIO's conference call to discuss our financial results clinical, and business updates for the fourth quarter and full year 2022. 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. Joining us for the Q&A portion will be Karen Youse, our head of R&D. Today, after the market closed, we issued a press release providing our fourth quarter 2022 and full year 2022 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 Gritstone'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 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?

Thank you, George, and good afternoon, everybody. Let me begin by first thanking our entire team for the tremendous progress that we made in 2022. I'm proud of the work we've accomplished, which started seven years ago with the ambition to take the next big step in cancer immunotherapy. We're now just months away from seeing early data from the first randomized trial testing our hypothesis. This is an incredibly exciting time for Gritstone and a big year for personalized cancer vaccines. The prospect of opening up most common solid tumors to the survival benefits of immunotherapy lies immediately ahead of us at Gritstone. With preliminary proof of concept data from our randomized controlled granite study in colorectal cancer expected in the fourth quarter of this year. If positive, these data could be transformational to the field and would encourage us to develop our platform in other common cold solid tumors, such as ovarian, prostate, and breast cancers, which remain largely refractory to simple immune checkpoint blockade and still account for a huge number of deaths from cancer every year. The top-line data shared by Moderna and Merck in December of 2022 are very encouraging for our product concept. And these data provide initial proof of concept for a neoantigen-based personalized cancer vaccine approach, albeit within the hot tumor context of melanoma. In total, randomized data from the three big players in the field, ourselves, Moderna, and BioNTech, are expected in 2023. As I mentioned at the outset, this is an exciting year for personalized cancer vaccines. So let's dive into our work in oncology. First, I'll address GRANIT, our fully individualized vaccine program. Let's step back and remind ourselves of the therapeutic hypothesis that underpins this program and the clinical data we've generated in support of it. Most patients with solid tumors have immunologically cold tumors wherein there is no evidence of immune system recognition of tumor neoantigens, no detectable neoantigen-specific cytotoxic T cell response, and thus no T cell substrate for checkpoint inhibitors to work on, leading to their relative inactivity as therapeutics in such patients. Our original idea was, and our approach remains, to identify tumor neoantigens and build vaccines containing these antigens, and then deliver them to patients alongside checkpoint inhibitors to induce strong neoantigen-specific DD8 T cells, also known as cytotoxic T cells. Once administered and generated, these T cells could then traffic to tumors, meet their antigen, proliferate, and kill tumor cells, leading to clinical benefit. This approach was described in our Nature Medicine paper published in August of 2022. We've been diligently working on each step in this chain and have shown positive results in patients with advanced disease with a focus on colorectal cancer. Specifically, we have shown the following. First, we can predict tumor neoantigens with high accuracy, a positive predictive value of over 75% at this point, and we continue to refine and improve our prediction model continuously. Secondly, in patients with no detectable neoantigen-specific T cells at baseline, our simple vaccination schedule elicits strong responses, primarily CD8 T cells, which can be readily detected in blood using traditional assays such as LSPOT. Thirdly, these neoantigen-reactive T cells traffic into tumors and proliferate, changing the T cell composition of the tumors and, critically, turning cold tumors into hot ones. Fourthly, these T cell responses are associated with tumor cell destruction. as measured by reductions in traditional biomarkers, such as CEA and CA99, often elevated in advanced colorectal cancer patients, as well as parallel reductions in circulating tumor DNA, or ctDNA, an emerging biomarker of value to immunotherapy drug developers. These molecular responses have been observed in approximately half of the third-line colorectal cancer patients we treated. And finally, molecular response was then associated with extended overall survival, such that molecular non-responders experienced a median overall survival of 7.8 months, exactly as expected in this context, whereas molecular responders have not yet reached median overall survival, although it will exceed 22 months. So having observed the success of this approach in a single-arm study in advanced disease, we launched our randomized controlled phase 2-3 study in newly diagnosed metastatic colorectal cancer patients, whereby patients are randomized to receive maintenance therapy with standard of care 5-fluorouracil or 5-FU plus bevacizumab or 5-FU plus bevacizumab plus our granite immunotherapy. This is a registrational quality study discussed with FDA back in August 2021. and we are enrolling 80 subjects in the open-label Phase II component, with preliminary data expected in the fourth quarter of this year. We anticipate sharing both ctDNA and progression-free survival data, evaluated using both RESIST and iRESIST criteria, on patients completing at least four months of treatment. We then plan to discuss the results with FDA in the first half of 2024, to align on the appropriate primary efficacy endpoint and then move into the phase three components of the trial. On a related note, I'd like to acknowledge our industry, the clinicians, the patient advocates, and the regulators for the work currently being done to evaluate and corroborate the association between molecular response and extended overall survival. The draft guidance the FDA issued in mid-2022 regarding ctDNA as a potential predictor of response among early-stage cancer patients represented an important step forward, and the work being done across the industry to incorporate ctDNA into drug development and patient and treatment selection is ongoing. The burgeoning data and rapid adoption of ctDNA across healthcare sectors gives us conviction that we're following the right path for gridstone and for patients alike. With granite, note that this trial, which again is in a common and cold tumor type, potentially opens the door to a transformation in cancer immunotherapy. Put otherwise, if granite works in colorectal cancer, one of the hardest to treat cancers, it is reasonable to think it will work in many other solid tumor types. We believe that generation and or amplification of potent neoantigen-specific CD8 cytotoxic T cells is always a good thing for cancer immunotherapy and for cancer patients, and that potentially vaccines like granite may become a foundational component of solid tumor immunotherapy. If we're successful in this endeavor, biomanufacturing of personalized vaccines at scale will be a critical requirement. Importantly, recall that we manufacture our own vaccines at our GMP biomanufacturing facility in California. Our decision to manufacture in-house has offered us many strategic benefits since we built the facility several years back. Our manufacturing process continues to improve in efficiency and capacity as we plan to scale out for phase three with an eye to commercial scale. Now to SLATE, which is our product platform that leverages the same biology as granite, but seeks to do so in an off-the-shelf manner. Now, off-the-shelf vaccines are attractive in that they can be administered rapidly upon patient selection. The key issue for the field has been to identify shared tumor-specific antigens that can be included within an off-the-shelf product. The commonest shared neoantigens derive from mutant KRAS proteins. And this is where we began our SLATE program a few years ago. In September of last year, we shared initial results from the Phase I-II study of KRAS-directed SLATE in late-line patients. Just as in the Granite Phase I-II study, we observed induction of neoantigen-specific CD8 cytotoxic T cells across all tumor types evaluated in the study, including metastatic, microsatellite-stable colorectal cancer, and non-small-cell lung cancer. Also, as in granite, we saw molecular responses in roughly half of the valuable patients. The largest single group of patients had advanced non-small cell lung cancer, all refractory to checkpoint blockade. And in this group, molecular responses were associated with approximate doubling of overall survival compared with subjects who didn't experience molecular response. This is very consistent with what we observed in granite. And the symmetry of these observations across products and across tumor types is suggestive of consistent biology and true efficacy signal. Following the same playbook as with granite, our next step is to verify findings in a randomized controlled trial in newly diagnosed metastatic patients. And we're launching such a study later this year. BLATE is a fascinating program that will diversify over time as more shared tumor antigens are identified and included in our vaccines, enabling applications beyond just mutant KRAS patients. Underlining the notion that stimulation of tumor antigen-specific T cells is likely always a good thing, we've recently begun a clinical collaboration with Dr. Steve Rosenberg at the National Cancer Institute, combining his mutant KRAS-specific cell therapy with our mutant KRAS-specific vaccine. We're excited by the science behind this approach and believe there's significant potential for it to extend the benefit of vaccine and cell therapy to a potentially broad set of patients. Combinations of our vaccine with small molecule mutant KRAS inhibitors may also make sense, and this is an area of interest at Bridgestone. Now, on the infectious disease side of our business, we continue making strides in putting clinical data onto the self-amplifying mRNA or SAM RNA platform via CORAL, our program evaluating vaccines against SARS-CoV-2. Through our three phase one CORAL studies, we continue to demonstrate the potential broad utility of SAM RNA to serve as a next generation platform vector. In August 2022, we reported six-month neutralizing antibody data from the first two cohorts of our ongoing Coral Boost trial, which is evaluating our SAM RNA vaccines as a boost following Vagzevria and or mRNA primary series. While numbers are small, results showed in all observable patients, the strong neutralizing antibody responses originally reported in January of 2022 persisted without decay up to six months. In the fourth quarter, we were notified that our NIAID-sponsored CORAL-NIH study had completed enrollment, and we also shared additional interim data updates from our CORAL-BOOST and CORAL-CEPI studies. These additional data demonstrated robust and potentially durable neutralizing antibodies, along with CD8 T cell responses. Enrollment in the CORAL CEPI study is now complete, and we plan to share further data from these studies at the ECMID conference in Copenhagen in April. The mRNA is rapidly emerging as a well-tolerated, scalable, and widely applicable platform technology, likely with distinct characteristics versus first-generation mRNA. We believe the data we're generating against SARS-CoV-2 provide clinical proof of concept for the continued application of SAM RNA across a wide range of infectious diseases. Outside of SARS-CoV-2, our partnership with Gilead to develop a vaccine-based curative HIV immunotherapy treatment remains active and ongoing in a phase one study. Results from a preclinical study in non-human primates within this program were presented at CROI just last month. demonstrating strong and durable viral antigen-specific CD8 T cell responses, further augmented by immune checkpoint blockade. In addition to these clinical stage programs, we have exciting preclinical projects ongoing, including development of an optimal immunogen for a therapeutic human papillomavirus vaccine that is supported by the Gates Foundation. We're also researching an influenza vaccine, as well as a new combination vaccine against multiple respiratory viruses. We look forward to sharing additional updates on our infectious disease programs and research throughout the year. And finally, I'd like to address some recent developments related to our intellectual property position, which we believe to be a strong asset for Gritstone. In late 2022, we received two United States patents related to SAM RNA. One includes claims covering Gritstone's individualized cancer vaccine candidates within the Granite program. And the second includes claims covering antigen-encoding SAM RNA vectors in general and has broad applicability across Gridstone's candidates in oncology and infectious disease. Additionally, we received recently a third U.S. patent directed to Gridstone's proprietary chimpanzee adenovirus, or CHAD, vector, which is modified to improve viral production. We use CHAD to prime within our oncology programs, and it is a key asset in our granite strategy to turn cold tumors hot. We view these patents as critical parts of a competitive moat around our therapeutic strategies. These recent patents further strengthen our IP position, which also includes our EDGE platform, key for accurate cancer neoantigen prediction. I'll now turn over to Celia, who will provide more color on our financial results for the fourth quarter and for the full year of 2022. Celia?