Risovalisib

Taiho Pharmaceutical Co., Ltd. (hereinafter “Taiho”) and Haihe Biopharma Co., Ltd. (hereinafter “Haihe”) announced today that the two companies have entered into an exclusive license agreement regarding the development, manufacturing and commercialization of the PI3Kα (phosphatidylinositol 3-kinase alpha) inhibitor risovalisib (international nonproprietary name; development code: CYH33). Risovalisib is currently being submitted for manufacturing and marketing approval in Japan as a treatment for ovarian clear cell carcinoma by Haihe Biopharma K.K., a fully owned affiliate of Haihe. Under the license agreement, Taiho will obtain exclusive rights in Japan to develop, manufacture and commercialize risovalisib, and Haihe will receive an upfront payment, development and sales milestone payments, and royalties based on sales revenue from Taiho. Risovalisib is a novel, selective PI3Kα inhibitor developed by Haihe. In Japan, Haihe Biopharma K.K. submitted a New Drug Application in August 2025 for the anticipated indication of "advanced or recurrent ovarian clear cell carcinoma harboring PIK3CA gene mutations that has progressed after chemotherapy." Risovalisib was granted orphan drug designation by the Ministry of Health, Labour and Welfare in June 2025 in Japan. “We are pleased to announce that we will be entering into this partnership with Haihe, with whom we have already built a strong collaborative relationship. Through risovalisib, a new treatment option for patients with ovarian clear cell carcinoma, we will continue to work together with Haihe to further contribute to patients and healthcare professionals,” stated Masayuki Kobayashi, President and Representative Director of Taiho. “We are pleased to announce that we are entering into a partnership with Taiho, one of the leading oncology companies in Japan, regarding the PI3Kα inhibitor risovalisib. We hope our collaboration will be able to provide a promising treatment option for patients with ovarian clear cell carcinoma and other PI3Kα-associated diseases,” stated Dr. Jian Ding from Haihe, Academician of the Chinese Academy of Engineering. PI3Kα is protein that regulates key physiological processes such as cell proliferation, survival and metabolism. The function of PI3Kα is jointly regulated by the PIK3CA (encoding the catalytic subunit) and PIK3R1 (encoding the regulatory subunit) genes. Mutations of both genes can lead to abnormal PI3Kα function, thereby causing a variety of diseases. 1 In the field of cancer, activating mutations or gene amplification of PIK3CA, as well as inactivating mutations or gene deletions of PIK3R1, can lead to overactivation of PI3Kα, promoting the occurrence and development of tumors such as breast cancer, ovarian clear cell carcinoma, and colorectal cancer. 2 Therefore, PI3Kα becomes an important target for cancer targeted therapy. In addition, activating mutations of PIK3CA or inactivating mutations of PIK3R1 are also associated with the occurrence of various non-tumor diseases,3 further highlighting the important role of PI3Kα in various diseases. Ovarian clear cell carcinoma (OCCC) is a rare, highly aggressive subtype of epithelial ovarian cancer. It is estimated that there are approximately 3,500 OCCC patients per year in Japan.4-6 The frequency of PIK3CA gene mutations have been reported approximately 30-40% in OCCC.7 Compared to the more common serous ovarian carcinoma, OCCC exhibits distinct molecular features and has significantly lower response rates to platinum-based chemotherapy.8 For recurrent OCCC, no standardized treatment regimen exists, and the prognosis for it is markedly worse than that of serous ovarian carcinoma,9 highlighting a significant unmet clinical need. Genomic studies have revealed that PIK3CA gene mutations are highly prevalent in OCCC.7,10-12 These mutations are predominantly enriched in exon 9 (helical domain) and exon 20 (kinase domain), leading to aberrant activation of PI3Kα and its downstream signaling pathways, which drive OCCC tumorigenesis and progression.13-15 Therefore, PI3Kα represents a promising therapeutic target for OCCC. Taiho Pharmaceutical, a subsidiary of Otsuka Holdings Co., Ltd. ( https://www.otsuka.com/en/ ), is an R&D-driven specialty pharma focusing on the fields of oncology and immune-related diseases. Its corporate philosophy takes the form of a pledge: “We strive to improve human health and contribute to a society enriched by smiles.” In the field of oncology, in particular, Taiho Pharmaceutical is known as a leading company in Japan for developing innovative medicines for the treatment of cancer, a reputation that is rapidly expanding through their extensive global R&D efforts. In areas other than oncology, as well, the company creates and markets quality products that effectively treat medical conditions and can help improve people’s quality of life. Always putting customers first, Taiho Pharmaceutical also aims to offer consumer healthcare products that support people’s efforts to lead fulfilling and rewarding lives. For more information about Taiho Pharmaceutical, please visit https://www.taiho.co.jp/en/ Haihe Biopharma Co., Ltd. is a global, innovation-driven biopharmaceutical company headquartered in China, with operational hubs in the United States and Japan. The company is dedicated to the development of cutting-edge anti-cancer therapies. With fully integrated capabilities spanning drug discovery, development, manufacturing, and commercialization, Haihe Biopharma aims to deliver life-saving treatments to cancer patients around the world and features a globally minded management and R&D team focused on in-house innovation. Currently, Haihe Biopharma has two approved products: Gumarontinib (INN), approved in both China and Japan, and paclitaxel oral solution (RMX3001/DHP107), approved in China, along with a robust pipeline of additional drug candidates. 1. Fruman DA, Chiu H, Hopkins BD, et al. The PI3K Pathway in Human Disease. Cell, 2017,170(4):605-635. 2. Arafeh R, Samuels Y. PIK3CA in cancer: The past 30 years. Semin Cancer Biol, 2019,59:36-49. 3. Morin GM, Zerbib L, Kaltenbach S, et al. PIK3CA-Related Disorders: From Disease Mechanism to Evidence-Based Treatments. Annu Rev Genomics Hum Genet, 2024,25(1):211-237. 4. National Cancer Center, Cancer Information Service, Hospital-based Cancer Registry, National Aggregated Data 2023 5. Romero I, Robert C Bast Jr. Minireview: Human Ovarian Cancer: Biology, Current Management, and Paths to Personalizing Therapy. Endocrinology. 2012 April, 153(4): 1593-1602 6. Enomoto T. Report of the Gynecologic Oncology Committee. The Journal of the Japan Society of Obstetrics and Gynecology, 2019; 71(5): 669-724. 7. Itamochi H, Oishi T, Oumi N, et al. Whole-genome sequencing revealed novel prognostic biomarkers and promising targets for therapy of ovarian clear cell carcinoma. Br J Cancer. 2017 Aug 22; 117(5): 717-724. 8. Pectasides D, Fountzilas G, Aravantinos G, et al. Advanced stage clear-cell epithelial ovarian cancer: the Hellenic Cooperative Oncology Group experience. Gynecol Oncol. 2006 Aug; 102(2): 285-91. 9. Kajiyama H, Shibata K, Mizuno M, et al. Postrecurrent oncologic outcome of patients with ovarian clear cell carcinoma[J]. Int J Gynecol Cancer, 2012, 22(5): 801-806. 10. Yang Q, Zhang C, Ren Y, et al. Genomic characterization of Chinese ovarian clear cell carcinoma identifies driver genes by whole exome sequencing. Neoplasia. 2020 Sep; 22(9): 399-430. 11. Yamamoto S, Tsuda H, Takano M, et al. PIK3CA mutations and loss of ARID1A protein expression are early events in the development of cystic ovarian clear cell adenocarcinoma. Virchows Arch. 2012 Jan; 460(1): 77-87. 12. Ye S, Zhou S, Wu Y, et al. Genomic profiling of ovarian clear cell carcinoma in Chinese patients reveals potential prognostic biomarkers for survival. Ann Med. 2023 Dec; 55(1): 2218104. 13. R.L. Chandler, J.S. Damrauer, J.R. Raab, et al., Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling, Nat Commun, 6 (2015) 6118. 14. Zhang X, Deng H, Zhao X, et al. RNA interference-mediated silencing of the phosphatidylinositol 3-kinase catalytic subunit attenuates growth of human ovarian cancer cells in vitro and in vivo. Oncology 2009; 77:22-32. 15. Kinross K, Montgomery K, Kleinschmidt M, et al. An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice. The Journal of clinical investigation 2012; 122:553-7.