On April 25, 2024 Hyundai Bioscience reported its clinical development plan of oral "Niclosamide Metabolic Anticancer Drug" targeting cancer patients with intractable cancer caused by p53 gene mutations (Press release, Hyundai Bioscience, APR 25, 2024, View Source [SID1234642368]). Mutations in the p53 gene occur in almost all cancer types and cause intractable cancers such cases found in ovarian cancer, uterine cancer, esophageal cancer, etc.

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The p53 gene acts as the "guardian of the genome," detecting cellular DNA damage and inducing cell death. When mutated, the p53 gene loses its function, leading to resistance to existing anticancer drugs and rapid metastasis of cancer cells. While R&D attempts have been made to develop anticancer agents that target p53 mutated cancer cells, those attempts have failed to selectively kill p53 mutated cancer cells without damaging normal cells.

Previous researches have shown evidences that niclosamide is a promising metabolic anticancer agent. Niclosamide can induce cancer cell death by regulating cancer cell metabolic pathways and can resolve drug resistance and cancer cell metastasis while minimizing side effects. It also enhances anticancer effects when used in combination therapy with existing anticancer drug.

Niclosamide, however, has not been developed as an anticancer drug for over 60 years due to its low bioavailability and short half life. With its patented drug delivery system technology, Hyundai Bioscience succeeded in developing niclosamide as an oral anticancer agent by reaching the necessary drug concentration level (IC50) to inhibit the proliferation of most cancer cells at non-toxic (NOAEL) dose.

Recently, in a triple-negative breast cancer in vivo studies, Hyundai Bioscience demonstrated that the combination therapy group with oral niclosamide-based anticancer agent and docetaxel, the widely-used chemotherapeutic drug, showed 67% higher anticancer effects compared to the docetaxel-alone treatment group. Long-term (13 weeks) animal toxicity tests confirmed that the blood concentration when administering the No-observed-adverse-effect level (NOAEL) of Niclosamide was 7,888 ng/mL. Considering that the IC50 for most types of cancer cell is 65~654 ng/mL, niclosamide is expected to inhibit the proliferation of most cancer cell types even when administered at less than one-tenth of the NOAEL.

Sang-ki Oh, CEO of Hyundai Bioscience, stated, "Niclosamide-based metabolic anticancer drug candidate will be the first P53-targeting anticancer treatment that selectively kills p53 mutated cancer cells," and added, "Through our subsidiary ADM Korea, we plan to conduct clinical trials targeting cancer patients with intractable cancer caused by p53 mutations, which will be the first step of clinical development on niclosamide-based anticancer agent pipeline."

Jong-Eon Lim, CEO of ADM Korea, mentioned, "We plan to submit IND for a clinical trial that is designed to compare the combination therapy group with niclosamide-based anticancer drug and existing anticancer drugs treatment against the single-agent therapy group," and added, "With this clinical trial, we will advance into a biotech specialized in oral metabolic anticancer agent."