STAT3 x PDL1

SEOUL, South Korea, July 11, 2024. 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." About ADM Korea Inc. and Hyundai Bioscience ADM Korea Inc., a subsidiary of Hyundai Bioscience, is a biotechnology company that develops anticancer drugs and also a Clinical Research Organization (CRO) service company in South Korea. ADM Korea Inc. is listed on the KOSDAQ market (symbol: 187660). Hyundai Bioscience is a biotechnology company that develops new drugs based on its novel drug delivery system technologies to deliver active ingredients safely and efficiently to targeted areas of the human body. Founded in 2000, Hyundai Bioscience focuses on repurposing or expanding indications of existing drugs using its proprietary organic-inorganic hybrid technologies. Hyundai Bioscience is a public company listed on KOSDAQ (symbol: 048410) in South Korea. SOURCE ADM Korea Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

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. SEOUL, South Korea, July 11, 2024 /PRNewswire/ -- 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." About ADM Korea Inc. and Hyundai Bioscience ADM Korea Inc., a subsidiary of Hyundai Bioscience, is a biotechnology company that develops anticancer drugs and also a Clinical Research Organization (CRO) service company in South Korea. ADM Korea Inc. is listed on the KOSDAQ market (symbol: 187660). Hyundai Bioscience is a biotechnology company that develops new drugs based on its novel drug delivery system technologies to deliver active ingredients safely and efficiently to targeted areas of the human body. Founded in 2000, Hyundai Bioscience focuses on repurposing or expanding indications of existing drugs using its proprietary organic-inorganic hybrid technologies. Hyundai Bioscience is a public company listed on KOSDAQ (symbol: 048410) in South Korea. For more information, please contact Ms. Joobin Jung, Global PR Manager ([email protected]). SOURCE ADM Korea

-Trial-in-Progress poster provides overview on PEMDA-HN trial evaluating danvatirsen in combination with KEYTRUDA® (pembrolizumab), Merck's anti-PD-1 therapy, in patients with recurrent/metastatic HNSCC- LEUVEN, Belgium and STRASBOURG, France and PHILADELPHIA, June 2, 2024 /PRNewswire/ -- Flamingo Therapeutics ("Flamingo") today announced the presentation of a Trial-in-Progress poster at the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO 2024) taking place in Chicago, Illinois. Flamingo's lead oncology program, danvatirsen, is an oligonucleotide discovered by Ionis that selectively targets STAT3 and has shown clinical activity in HNSCC. PEMDA-HN (NCT05814666) is a multicenter, open-label, randomized study evaluating the efficacy and safety of danvatirsen in combination with pembrolizumab compared with pembrolizumab alone as first-line treatment of patients with recurrent/metastatic HNSCC whose tumor expresses PD-L1. Two-thirds of patients will be randomized to receive danvatirsen and pembrolizumab and one-third will be randomized to receive pembrolizumab alone. The primary endpoint of the study is overall response rate by RECIST 1.1 as assessed by the investigator. The secondary endpoints include safety, duration of response, disease control rate, progression free survival and overall survival. PEMDA-HN is being conducted at study centers in the United States, South Korea and the United Kingdom. ASCO poster details are as follows: Abstract#: TPS6113 Title: "PEMDA-HN, an open-label, phase II, randomized controlled study of danvatirsen plus pembrolizumab compared to pembrolizumab alone in first-line recurrent and/or metastatic head and neck squamous cell carcinoma (RM HNSCC)" Session Title: Poster Session – Head and Neck Cancer Session Date and Time: June 2, 2024, 9:00am CDT Presenting Author: Marshall R. Posner, MD, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai For more information, please visit the ASCO 2024 website. About Flamingo Therapeutics Flamingo is pioneering RNA-targeted therapies for oncology with a clinical-stage pipeline targeting undruggable transcription factors and long non-coding RNAs. Flamingo has an alliance with Ionis Pharmaceuticals and is supported by well-known biotechnology investors including Abrdn (formerly funds managed by Tekla Capital Management LLC), Andera Partners, Bpifrance Large Venture, Bpifrance through its FABS and Fonds Biothérapies Innovantes et Maladies Rares funds, Eurazeo - Kurma Partners, Perceptive Advisors, PMV, Pontifax, Sphera, and VIB. Flamingo has initiated a Phase II trial 'PEMDA-HN' evaluating the STAT3 targeting agent danvatirsen, in combination with pembrolizumab, in patients with head and neck squamous cell carcinoma (HNSCC). A Phase I investigator-initiated trial study has also been initiated evaluating danvatirsen as a monotherapy and in combination with venetoclax in AML/MDS patients. For more information on Flamingo, please visit: PEMDA-HN (head and neck cancer) on clinicaltrials.gov: Danvatirsen monotherapy followed by combination with venetoclax in relapsed/ refractory AML and MDS on clincaltrials.gov: Please engage with us on LinkedIn: . Flamingo Media and Investor Contact: Amy Conrad Juniper Point (858) 366-3243 [email protected] SOURCE Flamingo Therapeutics