Our first oncology product candidate, GRANITE, is a personalized neoantigen-based immunotherapy. It is being evaluated in the Phase 2 portion of a Phase 1/2 clinical study in combination with checkpoint inhibitors for patients with microsatellite stable colorectal cancer (MSS CRC) who have progressed on FOLFOX/FOLFIRI therapy and a second cohort for patients with gastro-esophageal cancer who have progressed on chemotherapy. GRANITE was granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of MSS CRC.
For each patient, our personalized immunotherapy will start with a routine clinical biopsy. We then utilize our in-house sequencing capabilities with the tumor sample 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 immunotherapy 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.
Routine FFPE clinical biopsy as input material
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 product candidate, SLATE, utilizes the same neoantigen 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, providing us with an off-the-shelf alternative to GRANITE. SLATE is being evaluated in the Phase 2 portion of a Phase I/2 clinical study in combination with checkpoint inhibitors for the treatment of non-small cell lung cancer in patients with relevant KRAS mutations who have progressed on prior immunotherapy, and for cancer types where a relevant TP53 mutation exists.
The routine clinical biopsy used to identify personalized patient mutations can also identify patients that have common mutations within their tumor from commercially available genomic panel sequencing. These common driver mutations have been shown to produce shared neoantigens as identified by Gritstone’s EDGE platform in a subset of patients. 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, an “off-the-shelf” therapy may be able to treat additional patients across multiple tumor types.
Gritstone has a program focused on the development of bispecific antibody (BiSAb) therapeutics using highly tumor-specific antigens, including neoantigens, shared between patients with various solid tumors. Our lead BiSAb candidate is currently in IND-enabling studies. The target of this lead program is CT83, a cancer-germline antigen which is highly expressed on certain solid tumors and has limited/low expression on normal tissues.
We are leveraging EDGE™ to define targets for T-cell receptor (TCR) directed cell therapies. These additional targets that were identified and validated by Gritstone EDGE™ enable us to partner with others or develop additional therapeutic approaches to redirect T cells onto tumors using these highly specific targets.
We have a collaboration with bluebird bio to identify tumor-specific targets and natural TCRs directed to those targets for use in bluebird bio’s established cell therapy platforms. bluebird bio will conduct all development, manufacturing and commercial activities. Gritstone will provide 10 tumor-specific targets across several tumor types and, in certain cases, TCRs directed to those targets to bluebird bio.
Gritstone is developing a second generation vaccine against SARS-CoV-2, the virus that causes COVID-19, with potential for both prolonged protection and potency, including against emerging Spike mutant forms of SARS-CoV-2.
Through a license agreement with the La Jolla Institute for Immunology (LJI), one of the leading global organizations dedicated to studying the immune system, we have access to validated SARS-CoV-2 antigens that have been identified through LJI’s studies of hundreds of patients recovering from COVID-19. Using these antigens and our proprietary Gritstone EDGE™ and vaccine platform technologies, Gritstone has developed a novel vaccine containing Spike (similar to first generation vaccines) but also additional viral antigens that offer good targets for T cell immunity. By targeting several viral antigens, some of which are highly conserved between viral strains (such as SARS and SARS-CoV-2), our vaccine may have pan-SARS/coronavirus potential to protect against future coronavirus pandemics.
Gritstone has conducted preclinical studies demonstrating that our SARS-CoV-2 vaccine can induce significant and sustained levels of neutralizing antibodies and T cells against the Spike protein, plus a broad T cell response against epitopes from multiple viral genes outside of Spike.
We have received a grant from the Bill and Melinda Gates Foundation to support the preclinical evaluation of the vaccine. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is supporting development of the Phase 1 clinical trial, which is expected to be conducted through the Infectious Diseases Clinical Research Consortium (IDCRC).
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 an HIV-specific therapeutic vaccine using Gritstone’s proprietary prime-boost vaccine platform, comprised of self-amplifying mRNA (SAM) 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, and the companies are preparing to advance the program into a Phase 1 clinical trial.