Taiho Pharmaceutical Co., Ltd. has exercised its option to develop and commercialize casdatifan (AB521), an investigational small molecule HIF-2α inhibitor, in Japan and certain territories in Asia excluding mainland China. The decision, announced in partnership with Arcus Biosciences, Inc., represents the fifth option exercise under their 2017 collaboration agreement and positions casdatifan for potential market entry in key Asian markets.
Targeting HIF-2α Pathway in Kidney Cancer
Casdatifan is designed as a small-molecule inhibitor of HIF-2α (Hypoxia Inducible Factor-2α), a master regulatory switch that activates hundreds of genes in response to low oxygen levels. In healthy cells, HIF-2α is turned off when oxygen levels return to normal. However, in the majority of patients with clear cell renal cell carcinoma (ccRCC), this shut-off mechanism is deficient, causing HIF-2α to remain activated even in the presence of oxygen and driving normal kidney cells toward malignancy.
The compound is engineered to provide deeper and more durable inhibition of the HIF-2α pathway compared to existing approaches, potentially addressing a fundamental driver of the most common form of kidney cancer.
Phase 3 Trial Progress
Arcus Biosciences is currently conducting PEAK-1, a global registrational Phase 3 study comparing the combination of casdatifan with a VEGFR-targeted tyrosine kinase inhibitor against monotherapy using a VEGFR-targeted TKI alone in patients with clear cell renal cell carcinoma. The randomized, placebo-controlled, double-blind, multicenter trial specifically evaluates casdatifan combined with cabozantinib versus placebo and cabozantinib in patients with advanced ccRCC.
Japan is expected to participate in the PEAK-1 study beginning in the first half of 2026, bringing the investigational therapy closer to Japanese patients who may benefit from this novel therapeutic approach.
Addressing Significant Medical Need
Clear cell renal cell carcinoma represents the most common type of kidney cancer in adults, accounting for 75-80% of all cases. The broader context reveals kidney cancer as a disease with rising worldwide incidence, estimated at 400,000 new cases annually and a mortality rate approaching 175,000 deaths per year. Current projections suggest the incidence will continue increasing over the next decade, emphasizing the urgency of developing new therapeutic options.
Expanding Strategic Partnership
Under the licensing agreement, Taiho will make an option exercise payment to Arcus, along with additional payments upon achievement of clinical, regulatory and commercialization milestones. If products from the program receive approval, Taiho will pay royalties on net sales.
This latest option exercise continues the expansion of Taiho's collaboration with Arcus, which has now encompassed five programs: casdatifan (HIF-2α inhibitor), etrumadenant (dual A2a/b adenosine receptor antagonist, exercised in 2018), zimberelimab (anti-PD-1, exercised in 2019), domvanalimab (anti-TIGIT, exercised in 2021), and quemliclustat (CD73 inhibitor, exercised in 2024).
The partnership reflects Taiho's strategic focus on oncology and immune-related diseases as an R&D-driven specialty pharmaceutical company, operating under the corporate philosophy of striving "to improve human health and contribute to a society enriched by smiles."
