Gritstone bio, Inc. (NASDAQ:GRTS) is a clinical-stage biotechnology company that aims to develop the world's most potent vaccines. The company was founded in 2015 and is headquartered in Emeryville, California, with a manufacturing facility in Pleasanton, California. Gritstone's mission is to expand the emerging benefits of immunotherapy to all patients with solid tumors, and the company is making significant progress towards this goal.
Business Overview
Gritstone's core focus is on the development of vaccine-based cancer immunotherapy product candidates using a heterologous prime (ChAd)/boost (samRNA) approach. The company's two clinical-stage oncology programs, GRANITE and SLATE, are aimed at inducing a substantial neoantigen-specific CD8+ T cell response using neoantigen-directed immunotherapies. GRANITE is an individualized neoantigen-based vaccine program for solid tumors, while SLATE is an "off-the-shelf" neoantigen-based vaccine program.In addition to its oncology programs, Gritstone is also advancing its infectious disease pipeline, which includes the CORAL program, a next-generation prophylactic program against COVID-19, and a collaboration with Gilead Sciences to develop a therapeutic vaccine against HIV. The company's infectious disease programs aim to deliver vaccine candidates that induce both B cell and T cell immunity, with the potential to drive potent and durable immune responses that can be applied for either protective or therapeutic benefit.
Financials
Gritstone's financial performance has been marked by significant investments in research and development to advance its pipeline of vaccine candidates. For the year ended December 31, 2023, the company reported annual revenue of $1.3 million, annual net loss of $138.5 million, annual operating cash flow of -$121.6 million, and annual free cash flow of -$126.2 million.In the first quarter of 2024, Gritstone reported a net loss of $40.4 million, compared to a net loss of $34.0 million in the same period of the prior year. The increase in net loss was primarily attributable to a decrease in collaboration revenue of $0.7 million, an increase in research and development expenses of $2.5 million, and an increase in general and administrative expenses of $1.8 million.
As of March 31, 2024, Gritstone had cash, cash equivalents, marketable securities, and restricted cash of $52.8 million. In April 2024, the company completed an underwritten public offering, resulting in gross proceeds of $32.5 million, bringing the company's pro forma cash, cash equivalents, marketable securities, and restricted cash to approximately $85.3 million.
Oncology Program Updates
Gritstone's lead oncology program, GRANITE, is a personalized neoantigen-based vaccine for solid tumors. In the first quarter of 2024, the company reported preliminary data from the ongoing randomized Phase 2 study of GRANITE in newly diagnosed metastatic microsatellite-stable colorectal cancer (MSS-CRC) patients.The preliminary data showed a trend towards progression-free survival (PFS) benefit, with a hazard ratio of 0.82 in the overall population. In a high-risk subgroup of patients with higher baseline circulating tumor DNA (ctDNA) levels, the PFS benefit was more pronounced, with a hazard ratio of 0.52, indicating a 48% relative risk reduction of progression or death with GRANITE versus the control arm.
Importantly, the company did not observe any evidence of pseudoprogression, which is a phenomenon where lesions grow at the beginning of treatment prior to shrinking, potentially leading to patients being incorrectly labeled as having progressive disease. This supports the use of PFS as a Phase 3 efficacy endpoint, which the company plans to discuss with the FDA at an end-of-Phase 2 meeting.
Gritstone expects to report mature PFS data and additional long-term ctDNA data from the ongoing Phase 2 study in the third quarter of 2024 and overall survival data in mid-2025.
The company's second oncology program, SLATE, is an "off-the-shelf" neoantigen-based vaccine program for solid tumors. In March 2024, Gritstone published interim results from a Phase 1 study of SLATE in the journal Nature Medicine, which demonstrated a novel immunodominance hierarchy of tumor neoantigens that was leveraged to develop SLATE-KRAS, a KRAS-directed candidate.
Infectious Disease Programs
In early 2021, Gritstone initiated two programs in infectious diseases: CORAL, a next-generation prophylactic program against COVID-19, and a collaboration with Gilead Sciences to develop a therapeutic vaccine against HIV.The CORAL program has comprised three Phase 1 clinical trials evaluating multiple samRNA candidates across various patient populations and settings. Results to date have demonstrated the induction and persistence of high neutralizing antibody levels through at least 12 months, as well as broad T cell responses.
In September 2023, Gritstone entered into a contract with the Biomedical Advanced Research and Development Authority (BARDA) to conduct a 10,000-participant, randomized Phase 2b comparative study to evaluate the efficacy, safety, and immunogenicity of the company's next-generation COVID-19 vaccine candidate against an approved COVID-19 vaccine. The company is currently preparing for this study, which is expected to be initiated in the fall of 2024.
Gritstone's collaboration with Gilead Sciences to develop a therapeutic vaccine against HIV is also progressing, with a Phase 1 trial ongoing. If Gilead decides to progress development beyond the Phase 1 study, Gritstone will receive a $40.0 million non-refundable option exercise fee.
Liquidity
As of March 31, 2024, Gritstone had cash, cash equivalents, marketable securities, and restricted cash of $52.8 million. In April 2024, the company completed an underwritten public offering, resulting in gross proceeds of $32.5 million, bringing the company's pro forma cash, cash equivalents, marketable securities, and restricted cash to approximately $85.3 million.The company's priority is driving the GRANITE program forward, and its operating expenses reflect this focus. On the infectious disease side, Gritstone has primarily funded its programs with non-dilutive outside capital, and the company is exploring strategic funding approaches to support its growing infectious disease programs and business.