Phase 1/2 Trial Interim Outcomes: Gritstone's SLATE Neoantigen Vaccine Platform

Gritstone bio, Inc., a clinical-stage biotechnology firm, has announced the publication of a study in Nature Medicine that details the development of its "off-the-shelf" neoantigen vaccine platform, SLATE. The study, titled "A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results," reveals a new hierarchy of tumor neoantigens, including KRAS, discovered during Phase 1 translational studies. This discovery led to the development of SLATE-KRAS, a vaccine candidate that targets KRAS and has shown improved immunogenicity over earlier versions in Phase 2 trials. The vaccine is currently under evaluation in a combination study with cell therapy conducted by Steven A. Rosenberg of the National Cancer Institute.

Andrew Allen, M.D., Ph.D., Co-founder, President, and CEO of Gritstone bio, emphasized the significance of the "off-the-shelf" or shared neoantigen approach for solid tumors, highlighting the company's mission to develop potent vaccines. He also mentioned the collaboration with Dr. Rosenberg, a prominent figure in the field, and the potential of SLATE as a complementary platform to GRANITE, Gritstone's personalized vaccine program.

Karin Jooss, Ph.D., Executive Vice President and Head of R&D at Gritstone bio, discussed the importance of understanding the mechanism and performance of therapeutic neoantigens for the success of neoantigen-directed immunotherapy. She highlighted the company's expertise in selecting tumor antigens and optimizing cassette design to elicit a potent immune response.

The interim results from the Phase 1 portion of the Phase 1/2 clinical trial (NCT03953235) were reported in Nature Medicine. The trial assessed the safety, tolerability, and immunogenicity of SLATEv1, an off-the-shelf vaccine for patients with advanced/metastatic solid tumors. SLATEv1 uses a heterologous ChAd68 followed by a samRNA-based vaccine regimen encoding 20 shared neoantigens targeting multiple recurrent mutations in oncogenes such as KRAS, TP53, BRAF, and CTNNB1. The neoantigens were identified using Gritstone's proprietary platform, EDGE™, and selected based on shared mutations and matched HLA frequencies in patient populations with solid tumors.

The study also indicated a previously unknown hierarchy of neoantigen immunodominance, which may affect the efficacy of multi-epitope shared neoantigen vaccines. This led to the development of SLATE-KRAS, which was evaluated in the Phase 2 portion of the clinical study. Initial Phase 2 data suggesting an increased vaccine-induced T cell response were presented in September 2022.

Gritstone's SLATE platform is designed to elicit a significant T cell response for patients with solid tumors, using the company's proprietary epitope identification platform (EDGE™) and vaccine vectors. Unlike the personalized GRANITE program, SLATE delivers shared neoantigens across a subset of cancer patients based on common gene mutations. The Phase 1/2 study showed positive results for SLATE-KRAS in patients with late-line non-small cell lung cancer and microsatellite stable colorectal cancer.

Gritstone bio, Inc. is focused on developing potent vaccines to treat and prevent viral diseases and solid tumors, with the aim of improving patient outcomes and eliminating disease. The company utilizes innovative vectors and payloads to train the immune system to attack critical disease targets.