Novel Ruthenium-Based Small Molecule

Molecular Structure

Sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)]. Formulated as a sterile lyophilized powder for intravenous infusion.

Molecular Structure

Mechanism of Action

Inhibits drug resistance, survival and proliferation by selectively inhibiting stress-induced upregulation of GRP78 in tumor cells.

Clinical Stage

Completed Phase 1 monotherapy study (N=46); Well-tolerated with a manageable safety profile including minimal hematological activity.

Clinical Development

Phase 1b clinical study with BOLD-100 in combination with FOLFOX in gastric, pancreatic, colorectal and cholangial cancers starting in 1Q20.

Potential Indications

Wide range of solid and liquid tumors. Initial clinical focus: gastric, pancreatic, and colorectal cancers.

The Right Technology

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.

BOLD-100: Synergism With Targeted And Cytotoxic Therapeutics

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Essential For Cancer Progression

Tumor Growth

GRP78 is required for the tumor to proliferate and invade normal tissue.1,2

Cell Survival

GRP78 moderates the death signaling pathways and increases cell survival.3,4


GRP78 levels are high in tumor associated blood vessels.5-7

Tumor Metastasis

Increased GRP78 allows the cancer cells to metastasize and grow at other sites .8-10

Drug Resistance

Increased levels of GRP78 are associated with drug resistance and increased cell survival.11,12

Tumor Immunity

Cell Surface GRP78 in T-cells in complex with TGF-β stabilizes Treg cells. Secreted GRP78 generates Treg cells.13-16

1 Plos One, 10, (5), (May 14, 2015) • 2 Nature Reviews, 14, 263-278 (2014) • 3 Antiox Redox, 11(9), 2307-2316 (2009) • 4 Biochem J, 434(2), 181-188 (2011) • 5 Cancer Res., 71(8), 2848-2857 (2011) • 6 Mol Cancer Res, 6, 1268-1275 (2008) • 7 Cancer Res, 69, 5537-5545 (2009) • 8 Clin. Cancer Res., 19, 2107-2116 (2013) • 9 Clin Exp. Metastasis, 23, 401-410 (2006) • 10 Cell Biol, 45, 987-994 (2013) • 11 Oncogene, 32, 805-818 (2013) • 12 Ann Surg Oncol, 17, 603-612 (2010) • 13 J Immunol, 185(6), 3529-3535 (2010) • 14 Immune.,128, 218-226 (2009) • 15 Haematol, 100, 377-384 (2015) • 16 J Immunology, 175: 2525-2533 (2005)

Gastric Cancer

  • 1.7% of cancers (28k), but 1.8% (11k) of cancer deaths in U.S.
  • 5-year survival rate of only 3.1% in advanced gastric cancer.
  • Significant unmet therapeutic need.
  • Orphan market in U.S., but 5th most common cancer worldwide.
  • Extremely high incidence in Pacific Rim (China, Japan, and Korea).

BOLD-100 Development Rationale

  • Moderate-risk, high-reward strategy supported by compelling data.
  • Limited competition, both in the U.S. and Worldwide.
  • Opportunity for Orphan Drug Designation (ODD).
    • Provides numerous benefits including opportunity for market exclusivity and better coordination with FDA.
    • Orphan applications with FDA and EMEA in process.
  • High GRP78 levels correlate with poor prognosis in gastric and esophageal cancers (Oncotargets and Therapy, 2017).

Pancreatic Cancer

  • 3.2% of cancers (54k), but 7.2% (48k) of cancer deaths.
  • 5-year survival rate of only 8.2%.
  • Significant unmet therapeutic need.

BOLD-100 Development Rationale

  • High-risk, high-reward strategy supported by compelling data.
    • BOLD-100 selectively inhibits stress-induced upregulation of GRP78 in pancreatic cancer cells.
    • Statistically significant improvement in survival in preclinical pancreatic cancer models in combination with Gemzar® (gemcitabine).
  • Limited competition, both in the U.S. and Worldwide.
  • Orphan Drug Designation (ODD) granted in Jun 2017.
    • Provides numerous benefits including opportunity for market exclusivity and better coordination with FDA.
    • Orphan applications with EMEA in process.
  • Opportunity for market exclusivity and better coordination with FDA.

Adding BOLD-100 To Standard-Of-Care Gemzar(R) (Gemcitabine) Significantly Extends Both Median & Overall Survival In Vivo.


Select Publications On Bold-100

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

Intellectual Property

BOLD-100 Is Protected By Robust Intellectual Property Worldwide

Composition of Matter

Method of Use

Manufacturing Process

Patent-Protected Territories

North America

  • United Stated
  • Canada


  • European Union

Pacific Rim

  • China
  • Japan
  • South Korea


  • Australia
  • Isreal
  • New Zealand