Trastuzumab Imbotolimod

Bolt's CEO Randall Schatzman and Chief Medical Officer Edith Perez, M.D., are being moved to “advisory roles.” In another tough day for biotech employees, Bolt Biotherapeutics and Tenaya Therapeutics both outlined plans to significantly scale back their workforces. Bolt’s plans were the most dramatic, with around 50% of staff being laid off and the company’s CEO and Chief Medical Officer being shunted to advisory roles. The moves are tied to a “strategic refocusing” that will also see the biotech halt development of trastuzumab imbotolimod. The company had been evaluating the immune-stimulating antibody conjugate (ISAC) in patients with HER2-positive cancer. The phase 2 study saw patients with colorectal, endometrial, gastroesophageal or breast cancer receive trastuzumab imbotolimod as a monotherapy, while some breast cancer patients received the drug in combination with Roche’s Perjeta. Bolt had unveiled phase 1 data at the European Society for Medical Oncology Congress in October 2023 that showed a 29% objective response rate—consisting of one complete response and three partial responses at the recommended phase 2 dose. In the company’s first-quarter earnings release yesterday, Bolt said a “strategic review … has determined that the program will not meet its pre-defined success criteria.” “Bolt will therefore be focusing resources on its next-generation ISAC programs,” the company added. The changes reach all the way to the top, with CEO Randall Schatzman and Chief Medical Officer Edith Perez, M.D., being moved to “advisory roles.” Chief Financial Officer Willie Quinn has been appointed CEO. Removing the trastuzumab imbotolimod program and half of the company’s employees should extend Bolt’s cash runway into the second half of 2026. This would allow for the completion of the phase 1 trial of the Dectin-2 agonist antibody BDC-3042, as well as fund the delivery of clinical data from BDC-4182, a next-gen ISAC targeting Claudin 18.2. “At Bolt, we set a high bar for advancing our programs, and while [trastuzumab imbotolimod] provided clinical validation for the ISAC mechanism, it did not meet our high bar for advancement,” newly appointed CEO Quinn said in the release. “With limited resources, we want to focus those resources on the best product candidates.” It’s not the first pipeline pivot at Bolt, which dropped an anti-tumor candidate called BDC-2034 in August 2022 over off-target toxicity concerns. Tenaya Therapeutics used its earnings release yesterday to outline “cost-containment measures” designed to fund clinical readouts from its two lead heart-focused gene therapies. As a result, the biotech is reducing its workforce by around 22%, with the changes due to be completed in the coming weeks. “The year is off to a strong start for Tenaya,” CEO Faraz Ali said in the release. “We remain laser-focused on dosing patients and generating clinical data for our TN-201 and TN-401 programs to reach value-creative milestones and on managing our overall resources to ensure we maintain sufficient runway to achieve those milestones.” Tenaya is enrolling patients in a phase 1b trial of TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy. The biotech is also due to start dosing patients in a phase 1 trial of TN-401, a gene therapy for another heart condition called PKP2-associated arrhythmogenic right ventricular cardiomyopathy, in the second half of the year.