• Encouraging progression-free survival data in overall population; continued follow-up needed to allow data to mature further, especially in low ctDNA subgroup where events accrue more slowly
  
• 21% relative risk reduction of progression or death with GRANITE vs. control in all treated population (HR=0.79 [95% CI, 0.42-1.50])
• 38% relative risk reduction of progression or death with GRANITE vs. control in low ctDNA subgroup (HR=0.62 [95% CI, 0.23-1.70]) 
• Strength of neoantigen specific T cell responses in GRANITE patients appears to associate with progression-free survival
• GRANITE was generally well-tolerated with no treatment discontinuations due to adverse events
• Overall survival data expected in 2H 2025 

EMERYVILLE, Calif., Sept. 30, 2024 (GLOBE NEWSWIRE) -- Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, today announced encouraging interim Phase 2 data from the ongoing Phase 2 study evaluating GRANITE, its individualized neoantigen targeting immunotherapy, in frontline microsatellite stable colorectal cancer (MSS-CRC). The randomized, controlled study is designed to evaluate the clinical benefit of maintenance therapy with GRANITE (GRT-C901/GRT-R902) in combination with immune checkpoint inhibitors in addition to fluoropyrimidine/bevacizumab versus fluoropyrimidine/bevacizumab alone.

Overall progression-free survival (PFS) data show an encouraging benefit for GRANITE patients (HR=0.79 [95% CI, 0.42-1.50]). As expected, the greatest benefit was observed in the 50% of patients with lower disease burden at study entry, as measured by circulating tumor DNA (ctDNA) at study baseline. (HR=0.62 [95% CI, 0.23-1.70]). Continued follow-up is needed to fully assess GRANITE effects and determine whether a plateau of improved PFS (indicating durable clinical benefit) is achieved. The most recent ctDNA assessments for the 20 patients who remain without disease progression (per RECIST) were supportive of potential benefit from treatment with GRANITE: 12 of 13 GRANITE patients had stable ctDNA titers below the assay limit of quantitation (LOQ); 4 of 7 control patients exhibited the same characteristic.

“We are excited by the potential of GRANITE to extend both progression-free and overall survival in a disease where relentless progression is the rule with existing therapies,” said Andrew Allen, MD, PhD, Co-Founder, President & CEO of Gritstone bio. “The field of neoantigen-targeting immunotherapy is evolving rapidly, and the focus is shifting to patients with lower volume disease. Notably, patients with newly diagnosed metastatic disease who have low ctDNA at study entry and thereby relatively low disease burden, could benefit from this type of immunotherapy. Success for immunotherapy typically manifests as an elevated plateau in PFS and overall survival Kaplan-Meier curves, and we may be seeing this in our low disease burden population. We need more time to let these data mature. The most recent ‘low and stable’ ctDNA measurements in most GRANITE patients are encouraging since that pattern is not typically seen in patients about to develop disease progression. The potential PFS benefit observed in MSS-CRC, a notoriously ‘cold’ tumor, suggests opportunity for even greater effects in tumors more typically amenable to immunotherapy.”

Dr. Allen continued, “These data support further exploration of GRANITE in frontline MSS-CRC and in other low burden (neo)adjuvant settings. With this new dataset in hand, we continue to actively explore several strategic and funding alternatives to rapidly advance our innovative immunotherapy for the benefit of patients.”

Concurrently, Gritstone announced that it has engaged Raymond James as its financial advisor to support the Company in exploring and reviewing potential value-maximizing strategies. Gritstone does not intend to discuss or disclose further developments regarding the exploration of strategic alternatives unless and until its Board of Directors has approved a definitive action or otherwise determined that further disclosure is appropriate or required by law.

Key Findings from Interim Phase 2 Data in Front-Line Metastatic MSS-CRC

Data cut as of August 19, 2024

104 patients were randomized 1:1 in the study: 69 patients (39 GRANITE arm, 30 control arm) are included in the treated analysis below. Demographics and clinical characteristics were balanced between arms (stage, sidedness, presence of liver metastases), with the vast majority (80%) of patients having liver metastases in the treated analysis. Thirty-five patients did not advance to study treatment after oxaliplatin, most commonly due to withdrawing consent (n=15), disease progression (n=8), and other reasons (n=12) (12 in GRANITE arm; 23 in control arm).

• Interim data demonstrated an emerging PFS benefit to all GRANITE recipients (study not statistically powered for PFS)
  • 21% relative risk reduction of progression or death with GRANITE vs. standard of care (SOC) control in all treated population (HR=0.79 [95% CI, 0.42-1.50])
  • 33% (13/39) GRANITE and 23% (7/30) of control patients remain on study and free of progression
    • Last ctDNA assessment is below the assay LOQ in 12/13 GRANITE and 4/7 control patients

• Clinical benefit was most notable in patients with low disease burden (defined as patients with ctDNA equal to or below the trial population median value at study entry)
  • 38% relative risk reduction of progression or death with GRANITE vs. SOC control with low ctDNA subgroup (HR=0.62 [95% CI, 0.23-1.70])
  • Low baseline ctDNA is a likely prognostic and predictive factor
    
    
• Immune data were consistent with clinical activity
  
  
  • Functional neoantigen-specific T cells were observed in all 16/16 GRANITE patients tested by ELISPOT
  • Association of PFS and peak ex vivo ELISPOT responses was apparent, suggesting that ex vivo ELISPOT may be a surrogate for PFS
    
    
• GRANITE demonstrated a favorable safety and tolerability profile
  
  
  • No patients discontinued study treatment due to an adverse event (AE)
  • Common adverse events were the mild systemic and local effects associated with any potent vaccine, i.e. transient flu-like illness
  • One treatment-related serious AE (fatigue) occurred in the GRANITE arm (patient continued GRANITE treatment without recurrence upon recovery)

Gritstone plans to review the PFS data with FDA in the coming months and agree on next steps to advance GRANITE, including a potential Phase 2 or 3 trial using ctDNA levels as eligibility criteria.

About Gritstone bio

Gritstone 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 Statements

This 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; our exploration of strategic alternatives; 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.

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