BOLD-100

Summarizing, BOLD-100 is identified as epigenetically active substance acting via targeting several onco-metabolic pathways. Identification of the lipid metabolism as driver of acquired BOLD-100 resistance opens novel strategies to tackle therapy failure.

P1b/2a, N=117, Active, not recruiting, Bold Therapeutics, Inc. | Recruiting --> Active, not recruiting

In addition, we showed that the antiviral activity of BOLD-100 is not specific for SARS-CoV-2, but also inhibits the replication of the evolutionarily divergent viruses Human Immunodeficiency Virus type 1 and Human Adenovirus type 5. This study identifies BOLD-100 as a potentially novel broad-acting antiviral drug.

Proven metallotherapeutics, such as cisplatin and oxaliplatin, alter immune responses as part of their multimodal mechanisms-of-action...These results show that BOLD-100 in combination with FOLFOX can induce immune responses, and that these immune responses may predict clinical outcome. Analysis of additional patient samples from the Phase 2 trial is ongoing.

P1b/2a, N=100, Recruiting, Bold Therapeutics, Inc. | Trial completion date: Dec 2023 --> Sep 2024 | Trial primary completion date: Dec 2022 --> Dec 2023

P1b/2a, N=100, Recruiting, Bold Therapeutics, Inc. | Phase classification: P1b --> P1b/2a | Trial completion date: Jan 2023 --> Dec 2023

Our studies demonstrated that BOLD-100 increases ROS production and Ca release from the ER, leading to ER stress activation and, ultimately, to cell death. Our in vitro data strongly suggest that BOLD-100 inhibits the growth of MPM cell lines, proposing the application as a single agent, or in combination with other standard-of-care drugs, to treat MPM.

P1b, N=80, Recruiting, Bold Therapeutics, Inc. | Trial completion date: Mar 2022 --> Jan 2023 | Trial primary completion date: Dec 2021 --> Dec 2022

Utilizing bladder cancer as a case study, subsequent combination testing of BOLD-100 in combination with fluorouracil or cisplatin demonstrated that BOLD-100 enhanced cell death across different bladder cancer cell lines through synergistic interactions with these standard-of-care agents...Collectively, BOLD-100 showed a unique sensitivity profile across a panel of over 300 cancer cell lines, identifying multiple potential indications for future development. Subsequent investigations into several cancer types of interest and drug combinations are ongoing.

BOLD-100, a ruthenium-based complex, sodium trans-[tetrachloridobis (1H-indazole) ruthenate (III)] (also known as IT-139, NKP1339 or KP1339), is a novel small molecule drug that demonstrated a manageable safety profile at the maximum tolerated dose and modest antitumor activity in a phase I clinical trial. In estrogen receptor negative (ER-) breast cancer cells, combination of BOLD-100 with a PARP inhibitor, olaparib, induced significant inhibition of cell growth and xenografts and increased gamma-H2AX. Thus, BOLD-100 is a novel DNA repair pathway targeting agent and can be used with other chemotherapies in ER- breast cancer.