• 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=41) and was subsequently granted an Orphan Drug Designation (ODD) in pancreatic cancer, with additional ODDs expected imminently. Bold Therapeutics expects to initiate one or more combination Phase 1/2 studies in 2Q19 at various sites in Canada and the United States.

BOLD-100: Synergism with Targeted and Cytotoxic Therapeutics

Therapeutic Cell Line Cancer Combination Index
CDDP A549 Lung 0.172
Paclitaxel LNCaP Prostate 0.219
Doxorubicin Hep3B Liver 0.252
Everolimus MKL-1 NET 0.354
5-FU HCT-116 Colon 0.36
Oxaliplatin Lovo Colon 0.493
Erlotonib A549 Lung 0.509
Sorafenib Hep3B Liver 0.536
Docetaxel LNCaP Prostate 0.543
5-FU Lovo Colon 0.597
Gemcitabine A549 Lung 0.647
CDDP HCT-116 Colon 0.687
Erlotonib BxPC3 Pancreatic 0.691
Docetaxel A549 Lung 0.724
CDDP N87 Gastric 0.757
Sorafenib A549 Lung 0.846
Gemcitabine PANC-1 Pancreatic 0.895
Paclitaxel A549 Lung 1.01
Gemcitabine Capan-1 Pancreatic 1.02
5-FU ZR-75-1 Breast 1.05
Docetaxel N87 Gastric 1.05
Paclitaxel N87 Gastric 1.1

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)

Novel Ruthenium-Based Small Molecule

Molecular Structure

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

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=41); Well-tolerated with a manageable safety profile including minimal hematological activity
Clinical Development
Adaptive basket trial in combination with Standard-of-Care (SoC), including both traditional chemotherapies and targeted therapeutics
Potential Indications
Refractory and metastatic disease: Initially gastric, pancreatic, and colorectal cancers
  • 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)
  • 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 and overall survival in vivo.

In Vivo Pancreatic Cancer Results

BOLD-100 is protected by robust intellectual property worldwide

  • Composition of Matter
  • Method of Use
  • Manufacturing Process


  • U.S. and Canada


  • European Union


  • China, Japan, and South Korea


  • Australia, Isreal, and New Zealand