Bolt Biotherapeutics Shares New Data for BDC-4182 and BDC-1001 at SITC Annual Meeting

Bolt Biotherapeutics, a clinical-stage biopharmaceutical company, has unveiled promising preclinical data for its latest immunotherapy candidate, BDC-4182. This next-generation Boltbody™ ISAC, targeting claudin 18.2, was presented at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in Houston, Texas.

BDC-4182 has shown remarkable effectiveness in preclinical studies, outperforming cytotoxic claudin 18.2 ADCs in syngeneic models. It also demonstrated the capability to eradicate tumors with low claudin 18.2 expression. Supported by these encouraging preclinical results, Bolt Biotherapeutics is looking forward to initiating clinical trials for BDC-4182 in 2025.

Dr. Michael Alonso, Senior Vice President of Research at Bolt Biotherapeutics, expressed optimism about the BDC-4182 data presented at SITC. He highlighted that the next-generation claudin 18.2 ISAC has shown superior efficacy compared to existing claudin 18.2 ADCs in syngeneic tumor models. The preclinical trials indicated that BDC-4182 not only exhibits potent anti-tumor activity but also has the ability to generate immunological memory, which could lead to durable cancer treatment responses.

The company has conducted extensive in vitro and in vivo experiments to evaluate BDC-4182's anti-tumor activity and safety profile. Tests involving a murine surrogate of BDC-4182 in xenograft and syngeneic tumor models demonstrated significant anti-tumor effects across various tumor types with differing levels of claudin 18.2 expression. Additionally, BDC-4182's tolerability was assessed in non-human primates, and the results indicated an acceptable safety profile consistent with TLR7/8 activation and claudin 18.2 targeting.

Key findings from these studies revealed that BDC-4182 has a superior efficacy profile compared to cytotoxic claudin 18.2 ADCs, exhibits broad anti-tumor activity, and promotes immunological memory. The safety profile of BDC-4182 in non-human primates suggests potential for combination therapies with checkpoint inhibitors, chemotherapy, and anti-angiogenesis agents used in first-line and second-line cancer treatments.

In addition to the BDC-4182 data, Bolt Biotherapeutics also shared insights from the Phase 1 dose-escalation trial of BDC-1001. This first-generation ISAC demonstrated notable immunological activity in patients with high HER2 antigen expression. Greater immune activation was correlated with clinical benefits, and pharmacodynamic changes were particularly significant in patients with HER2 IHC3+ tumors. The data supports the hypothesis that ISACs with enhanced immune activation could offer improved efficacy, prompting further exploration of next-generation ISACs.

Bolt Biotherapeutics remains committed to advancing its pipeline of innovative cancer treatments. In addition to BDC-4182, the company is developing BDC-3042, a first-in-class agonist antibody targeting Dectin-2 to activate macrophages. BDC-3042 is currently in a Phase 1 dose-escalation trial involving patients with various solid tumor types.

The company’s Boltbody™ ISAC platform capitalizes on the precision of antibodies combined with the innate and adaptive immune system to induce a robust anti-cancer response. Each ISAC candidate consists of a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant. This design aims to recruit and activate myeloid cells, initiating a feedback loop that increases the presence of activated immune cells in the tumor microenvironment, ultimately enhancing the immune response against cancer.

As Bolt Biotherapeutics continues its research and development efforts, the promising preclinical results of BDC-4182 and the learnings from BDC-1001's Phase 1 trial underscore the potential of Boltbody™ ISACs in providing effective and durable cancer therapies.