Bold Therapeutics: Defeating Cancer Drug Resistance
DESPITE SIGNIFICANT ADVANCES IN ONCOLOGY OVER THE PAST DECADE, DRUG RESISTANCE REMAINS A SIGNIFICANT CHALLENGE. Over time, almost all patients develop resistance to their treatments, rendering them less and less effective (‘acquired resistance’). In parallel, some cancer types and mutations are naturally resistant to certain types of therapies (‘inherent or intrinsic resistance’). Bold Therapeutics is addressing this unmet need in oncology with its first-in-class anti-resistance therapy, BOLD-100, which has the potential to significantly improve outcomes in a wide range of patients by defeating cancer drug resistance. Bold Therapeutics is a rapidly growing Vancouver-based biopharmaceutical company tackling some of the most difficult-to-treat cancer indications head-on. Founded in 2018, Bold is has already made substantial headway, including building a consortium of more than 50 international researchers studying BOLD-100, initiating a Phase 1b/2a clinical trial, and executing its first regional licencing deal for BOLD-100 with Hana Pharm Co. of South Korea. BOLD-100 is a first-in-class rutheniumbased small molecule drug with a unique multimodal pro-apoptotic mechanism-ofaction (MoA) effective against both sensitive and resistant cell lines. More specifically, BOLD-100 (1) alters the unfolded protein response (UPR) through selective GRP78 inhibition; and (2) induces reactive oxygen species (ROS) which causes DNA damage and cell cycle arrest. Collectively, these effects 78
fall | autumn 2021
BIOTECanada
result in cell death in both sensitive and resistant cancers. In a previously completed Phase 1a monotherapy study in 46 patients with advanced cancer, BOLD-100 was found to be safe and generally well-tolerated, with clear indications of biological activity. In October 2020, Bold initiated its second clinical study, a Phase 1b/2a study in advanced gastrointestinal cancers. BOLD-100-001 (clinicaltrials.gov/ct2/show/ NCT04421820) is an open-label, multicenter two-stage study designed to evaluate the safety and efficacy of