• IND for clinical study for combination therapy with hormone therapy in prostate cancer patients to be submitted in August, 2024.
• Niclosamide-based metabolic anticancer drug aims to block signaling pathways that allow cancer cells to evade anticancer effects, potentially solving the issue of drug resistance.

ADM Korea, a subsidiary of Hyundai Bioscience, announced on the 8th that the first clinical trial target population for its niclosamide-based oral metabolic anticancer drug will be 'prostate cancer patients resistant to hormone therapy.'

Metabolic anticancer drugs regulate the metabolic pathways of cancer cells to induce their death. The niclosamide-based metabolic anticancer drug not only regulates the metabolic pathways of cancer cells to induce their death but also blocks the signaling pathways of cancer cells that avoid anticancer effects, thus inhibiting drug resistance.

Currently used anticancer drugs, including hormone therapies, chemotherapies, targeted therapies, and immunotherapies, all fail to resolve the issue of cancer cell drug resistance that arises with long-term treatment. Cancer cell resistance refers to the phenomenon where cancer cells activate cell signaling pathways that help them evade the effects of anticancer agents through repeated drug administration, thereby decreasing the efficacy of the drugs. The biggest challenge in anti-cancer treatment is solving the problem of cancer cell drug resistance, but no drug has yet been developed to address this.

Niclosamide is a drug that has been identified to inhibit the Wnt/β-catenin and STAT3 cell signaling pathways, which are activated when cancer cells develop resistance to anticancer drugs, thereby suppressing cancer cell drug resistance. Numerous studies have shown that when niclosamide is used in combination with chemotherapies (such as SN38 and azacitidine), immunotherapies (PD-L1 Ab), targeted therapies (erlotinib), and hormone therapies (enzalutamide), the anticancer effects are superior to those of single-agent treatments. However, due to the longstanding issues of low absorption and short half-life, niclosamide has not been repurposed as an anticancer drug over the past 60 years.

CNPharm, which plans to enter into an exclusive license agreement with ADM Korea, has overcome these two issues with its patented technology, successfully repurposing niclosamide as an oral metabolic anticancer drug.

In a triple-negative breast cancer model animal study conducted by CNPharm, the combination treatment of the chemotherapeutic agent docetaxel and the niclosamide-based metabolic anticancer drug showed 67% greater anticancer effects compared to the docetaxel-only treatment group. Additionally, in a three-month animal toxicity study of the oral niclosamide-based metabolic anticancer drug, the blood concentration at the NOAEL (No Observable Adverse Effect Level) of niclosamide was 7,888 ng/mL, and cancer cell proliferation was found to be reduced by 50% at a concentration of less than one-tenth of NOAEL level (65~654 ng/mL) in in vitro study, confirming the drug's safety. The niclosamide-based drug is an oral medication offering convenience and ease of administration.

ADM Korea plans to conduct clinical trials combining existing treatments with the oral niclosamide-based metabolic anticancer drug for all terminal cancer patients who have developed resistance to existing anticancer drugs. Initially, in August, ADM Korea will submit an IND to the Ministry of Food and Drug Safety of the Republic of Korea for a clinical study combining hormone therapy and the niclosamide-based metabolic anticancer drug in prostate cancer patients resistant to hormone therapy. ADM Korea received a proposal for this combination therapy clinical study from a domestic prostate cancer expert in mid-May. ADM Korea decided to conduct the clinical trial on prostate cancer patients first, as the number of prostate cancer patients is steadily increasing, there is no suitable treatment for patients resistant to hormone therapy, the clinical trial period for prostate cancer is relatively shorter (taking about four weeks), and higher therapeutic effects compared to other cancers can be expected.

According to a recent paper published in the Lancet, the number of prostate cancer patients worldwide is expected to more than double from 1.4 million in 2020 to 2.9 million in 2040. The global prostate cancer market is predicted to reach approximately 29.8 trillion KRW by 2025.

Combining niclosamide with existing anticancer treatments is expected to solve the problem of drug resistance, significantly enhancing the effectiveness of anticancer therapy compared to single-agent treatments, and drastically improving the quality of life for cancer patients.

Vice President of ADM Korea Jin Geun-woo said, "The clinical trial is designed to verify the safety and efficacy of combining niclosamide-based metabolic anticancer drug and hormone therapy in prostate cancer patients over four weeks by observing PSA levels. According to Clinical Cancer Research article {20.12 (2014)}, in animal models with tumors resistant to secondary hormone therapies for prostate cancer, enzalutamide alone reduced tumors by only about 5%, while the combination of niclosamide and enzalutamide resulted in a tumor reduction of about 72%. The niclosamide-based metabolic anticancer drug will mark a historic turning point in prostate cancer treatment."