Bolt Biotherapeutics presents updated preclinical data for BDC-4182

Bolt Biotherapeutics (BOLT) presented updated preclinical data for BDC-4182, a next-generation Boltbody ISAC clinical candidate targeting claudin 18.2, and provided key learnings from its Phase 1 dose-escalation trial of BDC-1001 at the 39th Annual Meeting of the Society for Immunotherapy of Cancer, being held in Houston, Texas from November 6-10, 2024. BDC-4182 is a next-generation Boltbody ISAC clinical candidate targeting claudin 18.2, a clinically validated target in oncology with expression in gastric/gastroesophageal junction cancer, pancreatic cancer, and other tumor types. BDC-4182 has advanced into IND-enabling activities, supported by in vitro and in vivo experiments demonstrating potent anti-tumor activity in multiple preclinical models, with clinical trial initiation expected in 2025. In vivo assessment of anti-tumor activity was performed with a murine surrogate of BDC-4182 using xenograft and syngeneic tumor models with different levels of claudin 18.2 expression. The tolerability of BDC-4182 was also tested in non-human primates. Key findings are summarized below: BDC-4182 demonstrated superior efficacy compared to cytotoxic claudin 18.2 ADCs. BDC-4182 demonstrated anti-tumor activity in a wide range of tumor models and elicits immunological memory. BDC-4182 has an acceptable safety profile in NHPs with findings consistent with TLR7/8 activation and claudin 18.2 targeting. BDC-4182 toxicology profile may enable combinations with checkpoint inhibitors, chemotherapy and anti-angiogenesis agents used in first-line and second-line treatments. Key learnings from the Phase 1 dose escalation trial of BDC-1001 are summarized below. First-generation ISAC BDC-1001 demonstrated immunological activity in this first-in-human trial, particularly in patients with high HER2 antigen expression. Greater immune activation was associated with clinical benefit. Pharmacodynamic changes were observed in HER2 IHC3+ and HER2 IHC2+, with both the greatest increase and statistical significance in patients with HER2 IHC 3+ tumors. Data supports the hypothesis that an ISAC with enhanced immune activation could offer greater efficacy, warranting further testing in next-generation ISACs.