BDC-3042 is a first-in-class antibody that reprograms tumor-associated macrophages (TAMs) to attack tumor cells. BDC-3042 is a monoclonal antibody that binds to and agonizes dectin-2, a cell surface protein on tumor-supportive macrophages. The activation of these macrophages results in the production of pro-inflammatory cytokines, consistent with the characteristics of tumor-destructive macrophages. BDC-3042 has the potential to turn tumor-supportive macrophages into tumor-destructive macrophages to elicit a productive anti-tumor immune response. BDC-3042 has completed a dose escalation trial demonstrating safety and anti-tumor activity, particularly in non-small cell lung cancer at the highest dose tested.

• AACR 2025 Presentation: BDC-3042, a first-in-class Dectin-2 agonist, in patients with advanced malignancies: Results from the first-in-human dose-escalation study
• May 2025 Event: Bolt Biotherapeutics BDC-3042 Phase 1 Results and Corporate Update Call

Our BDC-3042 product candidate reawakens myeloid cells to attack tumor cells. We discovered an agonist monoclonal antibody that is capable of binding to and activating a pattern-recognition receptor (known as Dectin-2) on tumor-associated macrophages (TAMs) in a broad range of solid tumors. BDC-3042 works by repolarizing TAMs from tumor-supportive to tumor-destructive.

CEA refers to a specific carcinoembryonic antigen cell adhesion molecule also known as CEACAM-5 that is commonly found in gastrointestinal cancers such as colorectal cancer. Our lead CEA-targeted ISAC comprises a novel, fully human antibody with high affinity and selectivity to CEA, and not to other members of the CEACAM family, conjugated to a proprietary next-generation TLR7/8 agonist via a non-cleavable linker. This ISAC drives efficient phagocytosis of CEA-positive tumor cells by myeloid cells and stimulates production of critical immune-activating cytokines including IL-12p70, IFNg, and TNFa. In vivo, tumor growth inhibition in xenograft models demonstrates induction of myeloid cell-mediated anti-tumor activity. In a CEA transgenic syngeneic mouse model, treatment with our lead ISAC results in complete tumor regression with development of immunological memory and epitope spreading as demonstrated by failure of CEA-positive cell line and CEA-negative parental cell line to form tumors upon rechallenge. Our lead CEA ISAC was well-tolerated at the highest dose tested, 15 mg/kg, in a non-GLP toxicology study.

• SITC 2025 Presentation: Preclinical evaluation of a highly efficacious CEACAM5 (CEA) ISAC comprising a novel CEA-specific monoclonal antibody and TLR7/8 agonist
• AACR 2025 Presentation: A highly efficacious next-generation CEACAM5 (CEA)-targeted ISAC for the treatment of colorectal, pancreatic and lung tumors

Our 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. Preclinical studies show that it can directly activate PD-L1-positive antigen-presenting cells resulting in the secretion of pro-inflammatory cytokines and stimulation of powerful T cell responses. In vivo, the PD-L1 ISAC elicits complete tumor regression and immunological memory in multiple syngeneic models. Mechanistic studies have demonstrated that our PD-L1 ISAC can generate complete responses in models where PD-L1 is only expressed on the immune cells, as well as in models where PD-L1 is only expressed on the tumor cells.

• SITC 2025 Presentation: Discovery of a PD-L1-directed ISAC optimized for the activation of PD-L1-expressing myeloid cells to drive potent antitumor immune responses
• AACR 2025: PD-L1-directed ISACs target host immune cells to drive powerful antitumor immune responses in a manner distinct from conventional PD-1/PD-L1 blockade