Core Insights - Bolt Biotherapeutics announced promising preclinical results for its next-generation Boltbody™ Immune-Stimulating Antibody Conjugates (ISACs) targeting CEACAM5 and PD-L1 at the AACR Annual Meeting [1][2] - The CEA-targeted ISAC demonstrated complete and durable anti-tumor responses in mice and was well-tolerated in non-human primates (NHPs) [2][5] - PD-L1 ISACs showed the ability to activate and reprogram PD-L1-expressing myeloid cells, promoting both innate and adaptive anti-tumor immunity [5][6] Group 1: CEA-targeted ISAC - The CEA ISAC is designed with a fully human antibody that specifically targets CEACAM5, commonly found in gastrointestinal cancers [2][4] - It enhances phagocytosis of CEA-positive tumor cells and stimulates the production of immune-activating cytokines such as IL-12p70, IFNg, and TNFa [2][5] - In a non-GLP NHP toxicity study, the CEA ISAC was well-tolerated at doses up to 15 mg/kg, with no significant drug-related adverse events observed [5] Group 2: PD-L1 ISAC - The PD-L1 ISAC utilizes a novel human anti-PD-L1 antibody conjugated to a next-generation TLR7/8 agonist, targeting both tumor and immune cells expressing PD-L1 [3][5] - It has shown complete regressions and the induction of immunological memory in models resistant to PD-1/PD-L1 checkpoint inhibitors [5] - The efficacy of PD-L1 ISACs does not rely on the blockade of the PD-1/PD-L1 axis, suggesting a complementary mechanism to existing therapies [5] Group 3: Company Overview - Bolt Biotherapeutics is a clinical-stage biopharmaceutical company focused on developing novel immunotherapies for cancer treatment [7] - The company's pipeline includes BDC-3042, an agonist antibody targeting dectin-2, and BDC-4182, a next-generation Boltbody™ ISAC targeting claudin 18.2, with clinical trials expected to begin in Q2 2025 [7]
Bolt Biotherapeutics Presents Preclinical Results for Next-Generation Boltbody™ ISACs targeting CEA and PD-L1 at AACR Annual Meeting 2025