Bolt Biotherapeutics announces results for Boltbody ISACs at AACR meeting

Bolt Biotherapeutics (BOLT) announced preclinical results from its next-generation Boltbody ISACs targeting CEACAM5 and PD-L1 at the American Association for Cancer Research annual meeting. Key results with the next-gen CEA ISAC are below: antigen-dependent induction of immune-stimulating cytokines in human, NHP and mouse effector cells; complete responses in CEA transgenic syngeneic model demonstrates robust efficacy; induction of immunological memory demonstrates potential for durable responses; in a non-GLP NHP tox study, the next-generation CEA ISAC was well-tolerated with no significant drug-related adverse events observed up to 15 mg/kg, the highest tested dose. Bolt’s PD-L1 ISAC utilizes a novel human anti-PD-L1 antibody conjugated to a next-generation TLR7/8 agonist payload via a non-cleavable linker. This ISAC leverages a unique mechanism of action due to its ability to target both tumor and immune cells that express PD-L1. PD-L1 ISACs directly activate and reprogram PD-L1-expressing myeloid cells in the TME to promote innate and adaptive antitumor immunity; PD-L1 ISACs elicit complete regressions and immunological memory in models that are resistant to PD-1/PD-L1 checkpoint inhibitor therapy; mechanistic studies indicate that PD-L1 expression by either tumor or immune cells is sufficient to drive antitumor efficacy; blockade of the PD-1/PD-L1 axis is not required for PD-L1 ISAC efficacy but may be a supportive mechanism and complementary combination strategy; favorable safety profile was demonstrated in non-GLP NHP toxicology studies supporting use in combination with SoC therapies & other agents.