TLR7 agonists/TLR8 agonists(Bristol Myers Squibb)

Bolt Biotherapeutics announced it is slashing its workforce by about 50% and terminating development of its lead cancer drug trastuzumab imbotolimod (BDC-1001) after determining the programme would not meet predefined success criteria. The changes also include a leadership shake-up, with CEO Randall Schatzman and chief medical officer Edith Perez being moved to advisory roles, while chief financial officer Willie Quinn now steps in to lead the company.The decision to halt the Boltbody immune-stimulating antibody conjugate (ISAC) programme follows a strategic review by Bolt. Trastuzumab imbotolimod, a HER2-targeting biosimilar of Herceptin (trastuzumab) conjugated with a proprietary TLR7/8 agonist, was being evaluated as a single agent or together with Bristol Myers Squibb's Opdivo (nivolumab) in a Phase I/II study of patients with HER2-positive solid tumours, including breast, colorectal, endometrial and gastroesophageal cancers.Data from a Phase I study presented at last year's European Society for Medical Oncology (ESMO) meeting showed a response rate of 29% with trastuzumab imbotolimod at the proposed Phase II dose. One patient with salivary gland cancer achieved a complete response in the monotherapy arm, while three partial responses were observed, including one in the monotherapy arm for biliary tract cancer and two in the combination arm for colorectal and ovarian cancer.With trastuzumab imbotolimod sidelined, Bolt plans to shift resources to its next-generation ISAC pipeline, including BDC-3042, a Dectin-2 agonist antibody currently in Phase I testing across multiple solid tumours. The company also aims to deliver clinical data for BDC-4182, a next-gen ISAC targeting Claudin 18.2 that's under development in gastric and pancreatic cancers.Bolt expects the moves to extend its cash runway into the second half of 2026, which will allow it to fund its way through those two goals for BDC-3042 and BDC-4182.Meanwhile, other executive changes include Grant Yonehiro being promoted to chief operating officer, while other promotions include Dawn Colburn becoming senior vice president of clinical development and Michael Alonso named as senior vice president of research.