Different problem, same result for Bolt

A year after scrapping trastuzumab imbotolimod owing to insufficient clinical activity, Bolt Therapeutics has apparently seen too much activity with a second molecule, BDC-4182. Both setbacks have elicited the same response, however, with the company on Wednesday slashing staff by 50%, just as it did in May 2024. This is to conserve cash after BDC-4182 generated such a strong immune response at the first dose levels tested clinically that Bolt has had to implement step-up dosing; as a result data from this trial are now expected in the third quarter of 2026, rather than during the first half of next year. BDC-4182, which targets Claudin18.2, is the latest attempt by Bolt to develop a so-called immune-stimulating antibody conjugate (ISAC), a strategy that's already caused the collapse of one company, Silverback Therapeutics. Despite this precedent, and the failure of trastuzumab imbotolimod, Bolt has limped on with a micro-cap valuation, first trumpeting attempts to develop an anti-Caprin-1 ISAC (these have yet to bear fruit) and then moving BDC-4182 into the clinic. Its pipeline also includes a non-ISAC Dectin-2 agonist MAb, BDC-3042, whose further development depends on finding a partner. Selected ISACs using TLR agonist payloadsProjectTumour antigenPayloadCompanyStatusBDC-4182Claudin18.2TLR7/8 agonistBolt BiotherapeuticsPh1/2 gastric cancer trialPF-08046037PD-L1TLR7 agonistPfizerPh1 trial +/-sasanlimabTAC-001CD22TLR9 agonistTallac TherapeuticsPh1 Incline-101 solid tumour trialGQ1007HER2TLR7/8 agonistGeneQuantum HealthcarePh1 solid tumour trial in AustraliaIBI3007TROP2TLR7/8 agonistInnovent BiologicsPreclinical poster at AACR 2024DN027262HER2TLR8 agonistDe Novo PharmatechPreclinical poster at SITC 2024TAC-003Nectin-4TLR9 agonistTallac TherapeuticsPreclinical poster at SITC 2023UnnamedClec2DTLR9 agonistImmunitas TherapeuticsPreclinical poster at SITC 2023Tusamitamab R848CEACAM5TLR7/8 agonistSanofiPreclinical poster at AACR 2023BDB101PD-L1TLR7/8 agonistEikon TherapeuticsPreclinical poster at AACR 2023BDB102HER2TLR7/8 agonistEikon TherapeuticsPreclinical (last mention in 2023)Source: OncologyPipeline.