Gritstone ramps up bispecifics with new antibody therapeutics chief

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.

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."

"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.

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