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Astellas Pivots Away from XTANDI, Betting Big on KRAS Degraders and Gene Therapy

Astellas Pharma's Q4 FY2025 earnings call, held April 27, 2026, revealed a company accelerating its transition away from Xtandi (enzalutamide) dependence through a concentrated set of late-stage pipeline bets. Setidegrasib (ASP3082)'s KRAS G12D degrader franchise, Padcev (enfortumab vedotin)'s bladder cancer expansion, and the broader Claudin 18.2/retinal disease franchises are emerging as key pillars of Astellas’ post-Xtandi growth strategy. The call was held on April 27, 2026.

Key Strategic Signals

[Setidegrasib / KRAS G12D TPD Franchise]: Astellas' targeted protein degradation program has expanded into a multi-indication franchise. A Phase III study in first-line PDAC was initiated during FY2025, and a second Phase III in second-line or later NSCLC is now under preparation following POC achievement in that indication. A follow-on pan-KRAS degrader, ASP5834, has also entered clinical development, executives said.

[ASP2957 / Gene Therapy]: Astellas confirmed a strategic hold on AT132 (resamirigene bilparvovec), its original gene therapy for X-linked myotubular myopathy (XLMM), following the clinical entry of successor ASP2957, which uses a novel muscle-targeted AAV capsid enabling a starting dose approximately 100-fold lower than AT132. Management said the shift was deliberate and that AT132 has been impaired on the balance sheet.

[ASP2138 / Claudin 18.2 Franchise Expansion]: ASP2138 achieved POC in gastric and gastroesophageal junction adenocarcinoma, and Astellas said Phase III initiation in first-line gastric cancer is planned for the first half of FY2026. The company also in-licensed VIR-5500 from Vir Biotechnology as a follow-on asset to reinforce its Claudin 18.2 position.

Analyst Pressure Points

[Setidegrasib vs. Revolution Medicines]: Analysts from UBS and Bernstein pressed management on whether Revolution Medicines' pan-KRAS inhibitor data, presented at AACR in April, represented a competitive threat to setidegrasib's KRAS G12D-specific approach. Chief R&D Officer Tadaaki Taniguchi acknowledged Revolution's data as favorable for the KRAS target overall, but argued setidegrasib's specificity translates to a cleaner safety profile, particularly lower skin and gastrointestinal adverse events, and easier combinability with chemotherapy in PDAC. He conceded the efficacy differentiation would only be resolved in late-phase data.

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[Pipeline Gene and Stem Cell Therapies]: With regards to development of the AT845 geographic atrophy gene therapy timeline, management disclosed that POC judgment for the product candidate remains pending, with a decision expected in H1 FY2026 following additional analysis. In contrast, ASP7317 (retinal pigment epithelial cell program, MA09-hRPE), under development for the treatment of Stargardt disease (juvenile macular degeneration) and geographic atrophy associated with dry age-related macular degeneration (dry AMD), did achieve POC, and discussions with regulatory authorities are ongoing on Phase III plans.

Forward-Looking Catalysts

[August 17, 2026 — Padcev PDUFA Date, Cis-Eligible MIBC]: The US FDA has granted priority review for Padcev in cisplatin-eligible muscle-invasive bladder cancer based on the EV-304 study, with a PDUFA date of August 17, 2026. Executives said the filing was accepted in April, and that EU and Japan regulatory decisions on related MIBC filings are also expected across the fiscal year, making this the most concentrated regulatory event cluster in the near-term pipeline.

[H1 FY2026 — Phase III Initiations for Setidegrasib (NSCLC) and ASP2138 (Gastric)]: Astellas guided for Phase III trial initiations for both setidegrasib in second-line or later non-small cell lung cancer and ASP2138 in first-line gastric cancer in the first half of FY2026. R&D expenditure for FY2026 is guided up approximately JPY 42 billion year-on-year to fund these initiations, with management indicating spend would remain at that level or higher as programs advance.


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