Incyte (INCY) ESMO 2025 Conference summary

Program highlights and scientific rationale

• Two solid tumor programs were featured: a TGFβ receptor 2 by PD-1 bispecific antibody (INCA33890) and a KRAS G12D inhibitor (INCB161734), both showing promising data at ESMO 2025 and highlighted at the conference.

• The TGFβ bispecific targets immunosuppressive TGFβ in the tumor microenvironment, especially relevant in MSS colorectal cancer, where immunotherapies have historically failed.

• The KRAS G12D inhibitor addresses a common and poor-prognosis mutation in pancreatic cancer, with no approved targeted therapies currently available.

• Both programs are designed for combination with standard-of-care chemotherapy to maximize patient benefit in first-line settings.

• The approach emphasizes cell-targeted inhibition to avoid systemic toxicity and leverages unique mechanisms for efficacy and safety.

Clinical data and efficacy

• The TGFβ bispecific demonstrated single-agent activity and a favorable safety profile in heavily pretreated MSS colorectal cancer, including patients with liver metastases.

• Confirmed responses were observed in 16 out of 105 MSS colorectal cancer patients, with durable responses and notable activity in liver metastases; ORR 15.2% at recommended doses.

• The KRAS G12D inhibitor showed a 34% response rate and 86% disease control rate in advanced pancreatic cancer, with manageable toxicity and no dose-limiting toxicities up to 1600 mg; 1200 mg selected for further development.

• Combination regimens with chemotherapy (gem abraxane and FOLFIRINOX) for both agents are ongoing, with initial safety data supporting further development.

• No significant impact of anti-drug antibodies on efficacy or pharmacokinetics was observed at the recommended doses.

Forward-looking plans and competitive positioning

• Phase III trials for the TGFβ bispecific in first-line MSS colorectal cancer and for the KRAS G12D inhibitor in first-line pancreatic cancer are planned for early 2026, with primary endpoint of progression-free survival.

• The TGFβ bispecific will be combined with FOLFOX and bevacizumab, targeting a broad patient population regardless of RAS status or tumor sidedness.

• The KRAS G12D inhibitor is positioned as a best-in-class agent, with the ability to combine with both major chemotherapy regimens, aiming for broad applicability.

• Ongoing work includes exploring biomarker-driven patient selection and potential combination of both agents in patients with overlapping mutations.

• Ongoing regulatory engagement and data collection support registrational programs, with a disciplined, data-driven approach focused on unmet need and competitive advantage.