Gritstone Oncology has appointed Jonah Rainey, Ph.D., to head up its bispecific antibody program as it moves into lead optimization. Rainey, who worked on bispecific antibodies for more than a decade and put in time at MacroGenics and MedImmune, will serve as vice president of antibody therapeutics.
Bispecifics, along with T-cell receptor (TCR) therapies, make up Gritstone’s youngest programs. Gritstone’s lead asset, a neoantigen cancer treatment called GRANITE-001, is headed for a phase 1/2 combination trial with Bristol-Myers Squibb’s Opdivo, thanks to funds raised in the company’s IPO.
The Bay Area biotech filed in August to raise up to $80 million in its Nasdaq debut and priced the offering at about $100 million at the end of September. The company has a second neoantigen treatment, SLATE-001, which is nearing the IND stage.
Gritstone’s approach involves identifying the tumor-specific neoantigens (TSNAs) on a patient’s tumor cells, using machine learning to determine which candidate is most likely to activate tumor-specific T cells and then treating the patient with personalized synthetic TSNAs. GRANITE-001 is given in two parts—first a priming adenoviral vector, followed by monthly boosters of an RNA vector, each containing the same 20 patient-specific TSNAs. SLATE-001 uses the same antigen delivery system as GRANITE-001, but instead of personalizing the treatment to each patient, it contains TSNAs that are shared by a subset of cancer patients, providing an off-the-shelf alternative to GRANITE-001.
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Like its other treatments, Gritstone’s bispecifics are based on its artificial intelligence EDGE platform, which identifies tumor-specific antigens—including neoantigens—that are shared between patients with different solid tumors. Gritstone has identified antibodies that bind to peptide-HLA (Human Leukocyte Antigen) complexes and behave like TCRs, activating T cells to attack tumor cells.
“Recent data with BiSAb [bispecific antibodies] in B cell malignancies have shown their ability to elicit a potent and targeted anti-tumor response,” said Gritstone CEO Andrew Allen, M.D., Ph.D., in a statement. “To extend application of BiSAb into solid tumors, we will first identify exquisitely tumor-specific HLAp targets shared between patients, and then develop antibodies that recognize these targets specifically.”
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“Under the leadership of Dr. Rainey, who has extensive expertise in antibody engineering and development, we are excited about the potential of TCR-mimetic-based bispecific antibodies to impact solid tumors using a 'drug-in-a-bottle' approach,” Allen said.