Sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)]. Formulated as a sterile lyophilized powder for intravenous infusion.
Inhibits drug resistance, survival and proliferation by selectively inhibiting stress-induced upregulation of GRP78 in tumor cells.
Completed Phase 1 monotherapy study (N=46); Well-tolerated with a manageable safety profile including minimal hematological activity.
Phase 1b clinical study with BOLD-100 in combination with FOLFOX in gastric, pancreatic, colorectal and cholangial cancers starting in 1Q20.
Wide range of solid and liquid tumors. Initial clinical focus: gastric, pancreatic, and colorectal cancers.
Bold Therapeutics' lead development candidate is BOLD-100, a novel first-in-class Cancer Resistance Pathway (CRP) inhibitor for the treatment of gastric, pancreatic and other cancers in combination with existing anti-cancer therapies.
BOLD-100 has demonstrated synergy in established preclinical models in combination with a wide variety of anti-cancer therapies including both traditional chemotherapies and targeted therapeutics.
BOLD-100 successfully completed a Phase 1 monotherapy study (N=46) and was subsequently granted an Orphan Drug Designation (ODD) in pancreatic cancer, with additional ODDs expected imminently. Bold Therapeutics is initiating a Phase 1b clinical trial on BOLD-100 in combination with FOLFOX in patients with advanced gastrointestinal cancers in early 2020.
GRP78 is required for the tumor to proliferate and invade normal tissue.1,2
GRP78 moderates the death signaling pathways and increases cell survival.3,4
GRP78 levels are high in tumor associated blood vessels.5-7
Increased GRP78 allows the cancer cells to metastasize and grow at other sites .8-10
Increased levels of GRP78 are associated with drug resistance and increased cell survival.11,12
Cell Surface GRP78 in T-cells in complex with TGF-β stabilizes Treg cells. Secreted GRP78 generates Treg cells.13-16
Burris HA, Bakewell S, Bendell JC, et al. Safety and activity of IT-139, a ruthenium-based compound, in patients with advanced solid tumours: a first-in-human, open-label, dose-escalation phase I study with expansion cohort. ESMO Open. 2017;1(6):e000154. Published 2017 Feb 23. View
Bakewell SJ, Rangel DF, Ha DP, et al. Suppression of stress induction of the 78-kilodalton glucose regulated protein (GRP78) in cancer by IT-139, an anti-tumor ruthenium small molecule inhibitor. Oncotarget. 2018;9(51):29698–29714. Published 2018 Jul 3. View
Lizardo MM, Morrow JJ, Miller TE, et al. Upregulation of Glucose-Regulated Protein 78 in Metastatic Cancer Cells Is Necessary for Lung Metastasis Progression. Neoplasia. 2016;18(11):699–710. View
Heffeter P, Atil B, Kryeziu K, et al. The ruthenium compound KP1339 potentiates the anticancer activity of sorafenib in vitro and in vivo. Eur J Cancer. 2013;49(15):3366–3375. View
Gifford JB, Huang W, Zeleniak AE, et al. Expression of GRP78, Master Regulator of the Unfolded Protein Response, Increases Chemoresistance in Pancreatic Ductal Adenocarcinoma. Mol Cancer Ther. 2016;15(5):1043–1052. View