The FDA has approved an Investigational New Drug Application (IND) amendment for Bold Therapeutics’ BOLD-100-001, allowing for the addition of clinical trial sites in the US. BOLD-100-001 is an open-label, multicentre two-stage study designed to evaluate the safety and efficacy of BOLD-100 in combination with FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) chemotherapy in patients with advanced gastric, pancreatic, colorectal and bile duct cancers.
BOLD-100-001 is currently enrolling patients at six clinical trial sites in Canada: Cross Cancer Institute in Edmonton, Alberta (PI Jennifer Spratlin); Princess Margaret Cancer Centre in Toronto, Ontario (PI Grainne O'Kane); Ottawa General Hospital in Ottawa, Ontario (PI Rachel Goodwin); Juravinski Cancer Centre in Hamilton, Ontario (PI Elaine McWhirter); and Jewish General Hospital and Royal Victoria Hospital in Montreal, Quebec (PIs Petr Kavan and Jamil Asselah, respectively).
"This FDA clearance is a major milestone for Bold Therapeutics as it allows us to more rapidly enroll patients and further diversify our patient population" said Jim Pankovich, EVP, Clinical Development. "Our corporate mission is to address significant unmet needs in oncology, and we are optimistic that BOLD-100 can meaningfully improve outcomes in patients with these difficult-to-treat cancers."
BOLD-100 is a first-in-class ruthenium-based small molecule therapeutic that (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 result in cell death in both sensitive and resistant cancers, giving BOLD-100 the potential to significantly improve outcomes in a wide range of both solid and liquid tumours in combination with other anti-cancer therapies ranging from traditional chemotherapies to targeted therapies to immuno-oncology agents.
Bold Therapeutics is a synthetic drug that can be manufactured efficiently at commercial scale, and Bold Therapeutics previously completed a 46-patient Phase 1 monotherapy study of BOLD-100 in patients with advanced solid tumours in which BOLD-100 was well-tolerated with minimal hematologic and neurologic side effects. This strong safety profile and remarkable preclinical synergy in combination with a wide range of existing anti-cancer therapies supported continued clinical development.
The FDA previously granted Orphan Drug Designations (ODDs) to BOLD-100 in both pancreatic and gastric cancer, and Bold Therapeutics expects to apply for Breakthrough Therapy Designations in a range of indications as preliminary clinical efficacy data becomes available late this year.
“Cancer is increasingly treated with combinations of therapies with complementary mechanisms-of-action rather than individual targeted therapies, against which cancer cells can readily adapt, quickly rendering them ineffective," said E Russell McAllister, Founder and CEO. "With a unique multimodal pro-apoptotic mechanism-of-action and a clean Phase 1 safety profile, BOLD-100 is positioned not to replace existing effective therapies, but to make them better – and, in some cases, perhaps much better. Preclinically, BOLD-100 has repeatedly generated unprecedented responses in these indications in vivo, such as extending mean survival times in an AsPC-1 gemcitabine-resistant pancreatic cancer model by a staggering 300% - and we are now in the process of testing to see if BOLD-100 can generate similar outcomes in man."