Gritstone bio (GRTS.Q) Status Update summary

Program overview and clinical rationale

• Lead program is a personalized neoantigen immunotherapy (GRANITE) in phase II for metastatic microsatellite stable (MSS) colorectal cancer, with mature PFS data expected this quarter and OS data in mid-2025.

• GRANITE aims to induce neoantigen-specific T cell responses using AI-driven neoantigen selection and a heterologous prime-boost vaccine system, combined with checkpoint inhibitors.

• Prior studies showed de novo induction of neoantigen-specific CD8 T cells in over 90% of advanced colorectal cancer patients, and the program has FDA Fast Track designation.

• The pivotal phase III study is planned for next year, with primary endpoints likely to be PFS or OS, pending FDA input.

• The approach targets the large unmet need in MSS colorectal cancer, which is resistant to checkpoint inhibitors alone.

Patient and advocacy perspectives

• Patient advocates emphasize the emotional, physical, and financial toll of current therapies, which are often outdated and have significant side effects.

• Quality of life and hope for long-term survival are top priorities for patients, who often exhaust standard options and seek clinical trials.

• Patient organizations like ColonTown and the Colorectal Cancer Alliance are actively involved in shaping research and supporting patients.

• The need for more effective frontline therapies is urgent, as most patients with metastatic disease eventually succumb despite current treatments.

Unmet need and treatment landscape

• Colorectal cancer is the second leading cause of cancer death globally, with rising incidence in younger adults and limited progress in treatment since the mid-2000s.

• Standard first-line therapies rely on decades-old chemotherapies, with modest improvements in survival and significant toxicity.

• Only 3-5% of patients (MSI-high) benefit from immunotherapy; the vast majority (MSS) do not respond to checkpoint inhibitors.

• Maintenance therapy after induction chemo is a key setting for testing new approaches, as patients are more likely to benefit from immunotherapy when disease is stable.