BOLT

Bolt Biotherapeutics, Inc. is a clinical-stage immuno-oncology company pioneering a novel class of immune-stimulating antibody conjugates (ISACs) designed to activate the innate immune system to fight cancer. Headquartered in Redwood City, California, Bolt has developed a proprietary technology platform that combines tumor-targeting antibodies with immune-stimulating molecules, creating therapies that simultaneously deliver immune activation directly to tumors while minimizing systemic exposure. This approach aims to overcome limitations of previous immune-oncology strategies by generating robust anti-tumor immune responses with improved safety profiles. Bolt's lead program is BDC-1001, an ISAC targeting HER2-expressing cancers including breast, gastric, and other solid tumors. BDC-1001 conjugates an anti-HER2 antibody with a Toll-like receptor 7/8 agonist that activates myeloid cells within the tumor microenvironment. This mechanism generates pro-inflammatory signals that recruit and activate immune cells, turn "cold" tumors "hot," and potentially overcome resistance to checkpoint inhibitors. Clinical trials are evaluating BDC-1001 as monotherapy and in combinations with checkpoint inhibitors across various HER2-expressing cancers. Bolt's pipeline includes additional ISACs targeting different tumor antigens. The immuno-oncology field has been transformed by checkpoint inhibitors, but many patients don't respond and many tumor types remain resistant. Bolt's ISAC platform represents a next-generation approach attempting to activate innate immunity within tumors, potentially complementing checkpoint inhibitors that primarily enhance adaptive immunity. The company's Boltbody technology platform enables creation of ISACs with optimized properties including tumor-selective immune activation and manageable safety profiles. Bolt faces competition from other innate immunity-targeting approaches, antibody-drug conjugates, and combination immunotherapy strategies. Success depends on demonstrating compelling clinical efficacy and differentiated safety compared to alternatives, establishing optimal combination regimens, advancing regulatory pathways, and ultimately proving that tumor-targeted innate immune activation provides meaningful clinical benefits for cancer patients. The company continues advancing its lead program through clinical development while expanding its ISAC pipeline.