For a description of our ongoing clinical studies, please visit clinicaltrials.gov. An overview of our compassionate use policy can be found here.
Our first oncology program, GRANITE, is a personalized neoantigen-based vaccine. GRANITE is being evaluated in a Phase 2/3 study evaluating GRANITE as a maintenance treatment in patients with newly diagnosed, metastatic microsatellite-stable colorectal cancer (MSS-CRC) patients who have completed FOLFOX- bevacizumab induction therapy. GRANITE was granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of MSS-CRC.
For each patient, GRANITE starts with a routine clinical biopsy. We then sequence the tumor sample in-house and apply our proprietary EDGE™ platform to derive a set of predicted patient-specific neoantigens likely to be presented on the patient’s tumor. Using these predicted neoantigens, we will then design a personalized vaccine containing the relevant neoantigens to be administered by simple intramuscular injection. We intend to deliver the immunotherapy in a community oncology setting where a vast majority of cancer patients are treated.
View Publication in Nature Medicine: “Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results.”
Routine FFPE clinical biopsy as input material
Tumor exome
Normal exome
Tumor transcriptome
Gritstone EDGE™
AI model for tumor antigen prediction trained on human tumor data
Patient specific predicted neoantigens inserted into Gritstone immunotherapy
Immunotherapy administered in conjuction with checkpoint inhibitors
Our second oncology program, SLATE, utilizes the same neoantigen identification capabilities and delivery system as GRANITE but contains a fixed set of neoantigens that are shared across a subset of cancer patients (rather than neoantigens unique to an individual patient).
A routine clinical biopsy can be used to identify patients that have common mutations within their tumor through commercially available genomic panel sequencing. These common driver mutations have been shown to produce shared neoantigens as identified by Gritstone’s EDGE platform. Similar to patient-specific neoantigens, shared neoantigens are a class of immune targets that present mutated peptides on the surface of the tumor cell. Because these neoantigens are shared, this “off-the-shelf” therapy may be able to treat additional patients across multiple tumor types.
We have a collaboration established with Gilead Sciences to research and develop a vaccine-based immunotherapy as part of Gilead’s efforts to cure patients with human immunodeficiency virus (HIV) infection. The companies are developing a curative HIV-specific therapeutic vaccine using Gritstone’s proprietary prime-boost vaccine platform, comprised of self-amplifying mRNA (samRNA) and adenoviral vectors.
Gritstone has conducted preclinical studies with our prime-boost vaccine technology utilizing simian immunodeficiency virus (SIV) derived antigens as model antigens. These antigens are very similar to those in HIV-1. The data demonstrated strong, durable and broad anti-SIV CD8+ T cell responses and T cell memory data. Gritstone and Gilead jointly performed further preclinical experiments that generated additional compelling data on the vaccine platform’s potential utility against HIV.
The CORAL program was initiated in 2021 in response to emerging limitations of first-generation COVID-19 vaccines, and today serves as proof-of-concept for our ability to drive more potent and durable responses than those of current vaccines in prophylactic applications. As seen among COVID-19 and other infectious diseases, immune responses can vary and viruses mutate and neutralizing antibodies wane, necessitating re-dosing (boosters). An approach capable of inducing potent, broad immune response could have utility across a variety of viral and infectious diseases.
Across multiple Phase 1 trials within CORAL, early results have demonstrated the potential ability of our vaccines to elicit potent and durable neutralizing antibody responses, and potent cytotoxic cellular responses against Spike and other conserved targets regions of the virus. These results have also provided early signals of the potential benefits of self-amplifying mRNA (samRNA).
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