GRANITE-001

Months after announcing the failure of a mid-stage trial for its personalized neoantigen vaccine in cancer, Gritstone bio reported more data that it plans to take to regulators. In the Phase 2 trial, Gritstone’s GRANITE vaccine in addition to immune checkpoint inhibitors and standard chemotherapy showed a 21% relative risk reduction in disease progression or death versus chemo alone in 69 patients with frontline microsatellite stable colorectal cancer (HR=0.79). The study was “not statistically powered” for progression-free survival. Even so, the company said Monday that signs of clinical benefit were greatest in the subset of patients with low disease burden, with that group seeing a 38% relative risk reduction of progression or death versus control (HR=0.62). It said it plans to keep following patients to establish a “plateau of improved PFS.” Gritstone’s shares $GRTS were down around 20% on Tuesday morning. Back in April, the Phase 2 trial missed its primary endpoint of short-term circulating tumor DNA response, with no difference seen between the treatment and control arms. At the time, CEO Andrew Allen said levels of the ctDNA biomarker dropped in patients in the control arm “for longer than we anticipated.” Nonetheless, Gritstone plans to review the PFS data with the FDA “in the coming months” and decide on next steps for its vaccine, which could include a Phase 2 or 3 study with ctDNA as eligibility criteria. But the company’s cash runway remains a challenge. It ended June with just $61.7 million in cash, equivalents, marketable securities and restricted cash. Gritstone disclosed Monday that it’s “reviewing potential value-maximizing strategies,” but won’t share any plans until it gets board approval. In March, the drugmaker laid off 40% of its staff after a delay for its Covid-19 vaccine trial. As a personalized vaccine, GRANITE is designed to target patient-specific neoantigens that are predicted using tumor sequencing and the company’s EDGE platform technology.

-- Preliminary randomized Phase 2 data suggest GRANITE (personalized neoantigen vaccine) could drive meaningful clinical benefit in front-line metastatic microsatellite-stable colorectal cancer (MSS-CRC); mature progression-free survival (PFS) data expected in the third quarter of 2024 -- -- Recent KOL event and patient advocacy engagements underscore the unmet need for new treatment options in metastatic colorectal cancer -- -- Presentations at AACR 2024 and ESCMID Global 2024 demonstrate the broad potential of Gritstone’s oncology and infectious disease vaccines -- -- Cash, cash equivalents, marketable securities and restricted cash of $61.7 million as of June 30, 2024 -- EMERYVILLE, Calif., Aug. 13, 2024 (GLOBE NEWSWIRE) -- Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, today reported financial results for the second quarter ended June 30, 2024 and provided recent corporate and clinical updates. “This is an exciting time for Gritstone, as we are on the cusp of unlocking important data about our promising new therapeutic modality in front-line metastatic microsatellite-stable colorectal cancer (MSS-CRC),” said Andrew Allen, MD, PhD, Co-founder, President & CEO of Gritstone bio. “Up to 95% of patients with metastatic CRC, the second most common cause of cancer death, are MSS. Delivering a new treatment option to these patients, who do not benefit from today’s immunotherapies, would be transformative. The emerging progression-free survival (PFS) benefit we reported in April is highly encouraging, especially in this tough to treat patient population. We have waited for these clinical data to mature and look forward to sharing the updated dataset next month. If we continue to see evidence of a clinical benefit with GRANITE, as measured by PFS, we believe new hope can be brought to patients who have not been helped by immune checkpoint blockade.” Dr. Allen added, "Along with advancing GRANITE in CRC, our team continues to innovate across our programs, reinforcing the potential of our underlying technologies. Our recent AACR presentation highlights the unique power of EDGE™, our proprietary neoantigen identification platform that underpins all our programs. Our recent presentation at ESCMID showcases the ability of our self-amplifying mRNA vector (samRNA) to induce long-lasting immune responses. Gritstone remains uniquely positioned to deliver on the promise of next-generation vaccine technologies to prevent, treat and eradicate disease.” Corporate Updates In April 2024, Gritstone completed an underwritten public offering resulting in gross proceeds of $32.5 million.In April 2024, Gritstone appointed Stephen Webster to its Board of Directors. A veteran finance executive with over 30 years in the biotechnology industry, Mr. Webster has held several key roles and been involved in multiple strategic transactions. Mr. Webster was the Chief Financial Officer of Spark Therapeutics from July 2014 until its acquisition by Roche for $4.3 billion in December 2019.In July 2024, Gritstone bio engaged the Colorectal Cancer Alliance and the Paltown Development Foundation 501(c)(3), the fiduciary for Colontown.org, as part of its effort to educate and empower patients living with colorectal cancer and their caregivers.In August 2024, Gritstone bio held a virtual KOL event to discuss the unmet need and potential role of GRANITE in metastatic microsatellite-stable colorectal cancer (MSS-CRC). The event featured J. Randolph Hecht, MD, Professor of Clinical Medicine and Director of the UCLA GI Oncology Program, and Howard Brown, CRC Survivor, Patient and Advocate. Details here. Clinical Program Updates Tumor-Specific Neoantigen Oncology Programs (GRANITE and SLATE)GRANITE – Personalized neoantigen vaccine programSLATE – “Off-the-shelf” neoantigen vaccine program Preliminary results (reported April 1, 2024) from the ongoing randomized Phase 2 study suggest GRANITE could drive meaningful clinical benefit in front-line metastatic microsatellite-stable colorectal cancer (MSS-CRC). Gritstone expects to report mature progression-free survival (PFS) data in 3Q 2024. Preliminary data, while immature, showed a trend of extended PFS in GRANITE-treated vs. control patients. Hazard ratio of 0.82 (18% relative risk reduction of progression or death with GRANITE vs. control) in the overall population, where clinical data are less mature ([95% CI, 0.34-1.67]; 62% censored)Hazard ratio of 0.52 (48% relative risk reduction of progression or death with GRANITE vs. control) in a fast-progressor, i.e. ‘high-risk’ group1, where clinical data are more mature ([95% CI, 0.15-1.38]; 44% censored). Too few events in the slow-progressor group at this early look to draw any efficacy conclusions.1Fast-progressor subgroup defined as baseline ctDNA above the median value (2%) for the control group (ctDNA quantified as mean variant allele frequency [VAF] at time of study randomization). Long-term circulating tumor DNA (ctDNA) data aligned with PFS trend and favored GRANITE vs. control patients EDGE™ predicts HLA Class I presentation with >80% accuracy. In April 2024, Gritstone presented an update on the predictive performance of both HLA Class I and HLA Class II presentation at the 2024 American Association for Cancer Research (AACR) Annual Meeting in San Diego, CA. The findings further Gritstone’s belief that EDGE is leading the field in neoantigen prediction.The clinical trial collaboration with the National Cancer Institute (NCI) to evaluate an autologous mutant KRAS-directed TCR-T cell therapy in combination with SLATE-KRAS, Gritstone’s KRAS-directed “off-the-shelf” vaccine candidate, is ongoing. The study is led by Steven A. Rosenberg, M.D., Ph.D., Chief of the Surgery Branch at the NCI's Center for Cancer Research and builds into the growing interest in combining tumor-antigen specific cell therapy with matched vaccines. Infectious Disease ProgramsCORAL – Next-generation SARS-CoV-2 vaccine program that serves as proof-of-concept for Gritstone’s samRNA platform and novel approach in infectious diseases Efforts to initiate a head-to-head Phase 2b study of Gritstone’s next-generation COVID-19 vaccine (the CORAL Phase 2b study) per the Biomedical Advanced Research and Development Authority (BARDA)2 contract continue. Gritstone will provide further updates as it is able.Follow up data from the Phase 1 CORAL study highlight the durability and potential broad utility of Gritstone’s samRNA COVID-19 vaccine. In April 2024, Gritstone presented 12-month follow up data from the Phase 1 CORAL-CEPI at ESCMID 2024. The results reinforced previous findings showing induction of broad and durable immune responses through 12 months. HIV – Collaboration with Gilead to research and develop vaccine-based HIV immunotherapy treatment The collaboration with Gilead to research and develop a vaccine-based HIV immunotherapy treatment continues under Gilead’s direction. Second Quarter 2024 Financial Results Cash, cash equivalents, marketable securities and restricted cash were $61.7 million as of June 30, 2024, compared to $52.8 million as of March 31, 2024. Research and development expenses were $20.8 million for the three months ended June 30, 2024, compared to $31.0 million for the three months ended June 30, 2023. The decrease of $10.2 million for the three months ended June 30, 2024, compared to the three months ended June 30, 2023 was primarily due to decreases of $3.2 million in personnel-related expenses, $3.2 million in laboratory supplies, $2.6 million in outside services, consisting primarily of clinical trial and other chemistry, manufacturing and controls related expenses and $1.2 million in facilities related costs. General and administrative expenses were $7.7 million for the three months ended June 30, 2024, compared to $6.7 million for the three months ended June 30, 2023. The increase of $1.0 million was primarily attributable to increases of $0.9 million in personnel-related expenses, including a $0.5 million increase of non-cash stock-based compensation, and $0.1 million in facilities related costs.Grant revenues were $0.9 million for the three months ended June 30, 2024. During the three months ended June 30, 2024, we recorded $0.9 million in grant revenue from CEPI. 2 This project has been supported in whole or in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under contract number 75A50123C00062. About Gritstone bioGritstone bio, Inc. (Nasdaq: GRTS) is a clinical-stage biotechnology company that aims to develop the world’s most potent vaccines. We leverage our innovative vectors and payloads to train multiple arms of the immune system to attack critical disease targets. Independently and with our collaborators, we are advancing a portfolio of product candidates to treat and prevent viral diseases and solid tumors in pursuit of improving patient outcomes and eliminating disease. www.gritstonebio.com Gritstone Forward-Looking StatementsThis press release contains forward-looking statements, including, but not limited to, statements related to our clinical and regulatory development plans for our product candidates; our expectations regarding the data to be derived in our ongoing and planned clinical trials; the timing of commencement of our future nonclinical studies, clinical trials and research and development programs; our ability to discover, develop and advance product candidates into, and successfully complete, clinical trials; and our plans and strategy regarding maintaining existing and entering into new collaborations and/or partnerships. Such forward-looking statements involve substantial risks and uncertainties that could cause Gritstone’s research and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including Gritstone’s programs’ clinical stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, Gritstone’s ability to successfully establish, protect and defend its intellectual property and other matters that could affect the sufficiency of existing cash to fund operations. Gritstone undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the company in general, see Gritstone’s most recent Annual Report on Form 10-K filed on March 5, 2024 and any subsequent current and periodic reports filed with the Securities and Exchange Commission. This press release concerns drugs that are under clinical investigation, and which have not yet been approved for marketing by the U.S. Food and Drug Administration. They are currently limited by Federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. Gritstone ContactsInvestors:George E. MacDougallGritstone bio, Inc.ir@gritstone.com Media:Dan Budwick1AB(973) 271-6085dan@1abmedia.com Gritstone bio, Inc.Condensed Consolidated Balance Sheets (unaudited)(In thousands) June 30, 2024 December 31, 2023Assets Current assets: Cash and cash equivalents $50,900 $62,986 Marketable securities 4,812 16,288 Restricted cash 1,274 2,299 Prepaid expenses and other current assets 3,724 5,862 Total current assets 60,710 87,435 Long-term restricted cash 4,695 5,290 Property and equipment, net 12,527 17,281 Lease right-of-use assets 64,001 66,839 Deposits and other long-term assets 609 924 Total assets $142,542 $177,769 Liabilities and stockholders’ equity Current liabilities: Accounts payable $4,132 $3,819 Accrued compensation 5,272 9,357 Accrued liabilities 856 1,213 Accrued research and development expenses 3,002 3,696 Lease liabilities, current portion 7,159 6,904 Deferred revenue, current portion 698 2,350 Warrant liability 2,782 — Total current liabilities 23,901 27,339 Other liabilities, noncurrent 1,117 709 Lease liabilities, net of current portion 54,829 57,727 Debt, noncurrent 40,506 40,144 Total liabilities 120,353 125,919 Stockholders’ equity: Preferred stock — — Common stock 24 22 Additional paid-in capital 745,510 711,386 Accumulated other comprehensive (loss) gain (3) 3 Accumulated deficit (723,342) (659,561)Total stockholders’ equity 22,189 51,850 Total liabilities and stockholders’ equity $142,542 $177,769 Gritstone bio, Inc.Condensed Consolidated Statements of Operations and Comprehensive Loss (unaudited)(In thousands, except share and per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Revenues: Collaboration and license revenues $57 $400 $106 $941 Grant revenues 864 1,555 2,557 3,456 Total revenues 921 1,955 2,663 4,397 Operating expenses: Research and development 20,811 30,967 53,852 61,481 General and administrative 7,698 6,716 16,200 13,461 Total operating expenses 28,509 37,683 70,052 74,942 Loss from operations (27,588) (35,728) (67,389) (70,545)Interest income 691 1,479 1,403 3,157 Interest expense (1,304) (985) (2,600) (1,828)Other income (expense) 4,805 (22) 4,805 (22)Net loss (23,396) (35,256) (63,782) (69,238)Other comprehensive loss: Unrealized loss on marketable securities (2) (73) (6) (45)Comprehensive loss $(23,398) $(35,329) $(63,787) $(69,283)Net loss per share, basic and diluted $(0.16) $(0.31) $(0.49) $(0.60)Weighted-average number of shares used in computing net loss per share, basic and diluted 143,296,662 114,929,523 130,843,943 114,676,261