INCYTE INVESTOR EVENT AT ESMO 2026 - MORPHOSYS AG

Explicit Guidance:

• INCB-890 (TGF-βR2 x PD-1): Top-line data expected for the Phase 3 NEXUS-0303 (Nexera) study in 2029.
• INCB-734 (KRAS G12D): Top-line data expected for the Phase 3 DAWN-0303 study in PDAC in 2028.
• INCB-734 (CRC): Enrollment for Phase 3 START study in second/third-line colorectal cancer planned to begin in the first half of 2027.
• INCB-734 (Adjuvant): Phase 3 adjuvant study in pancreatic cancer expected to initiate in 2027.
• INCB-890 (Adjuvant): Proof-of-concept adjuvant study in ctDNA-positive colorectal cancer is currently enrolling.

Business-Segment Outlook:

• Core Franchise Focus: Concentration on a "world-class solid tumor franchise" centered on gastrointestinal (GI) oncology, specifically colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC).
• Program Expansion (890): Moving from frontline MSS CRC to adjuvant settings; exploring head and neck, ovarian, and non-small cell lung cancer (NSCLC).
• Program Expansion (734): Leading indication is PDAC; expansion into second/third-line CRC; exploration of non-small cell lung cancer (NSCLC).
• Patient Population: Addressed indications cover approximately 250,000 new patients annually (120,000+ PDAC, MSS CRC, and CCNE1-overexpressing ovarian).
• Strategic Principle: Prioritizing frontline and adjuvant settings to maximize patient benefit and commercial opportunity; targeting high-incidence cancers with limited treatment options.

Market and Competitive Outlook:

• Competitive Positioning: Management states they are in a "co-lead" position with the primary competitor (AMG 510/sotorasib or adagrasib equivalents) regarding KRAS G12D inhibitors, citing faster enrollment and comparability in efficacy/safety.
• Differentiation Strategy:
  • INCB-890: Relies on "on-off" dual-inhibition mechanism targeting the TGF-βR2 receptor specifically within the tumor microenvironment (via PD-1 docking) to avoid systemic toxicity, unlike previous broad TGF-β kinase inhibitors or ligand traps.
  • INCB-734: Utilizes a "on-off" inhibitor mechanism targeting both GDP-bound and GTP-bound states of KRAS G12D for maximal target coverage (>95%), contrasting with "on-only" inhibitors.
• First-Mover Advantage: Management emphasizes the advantage of being the first to market to establish standard-of-care toxicity management protocols (specifically GI toxicity) and physician familiarity, noting that subsequent entrants must demonstrate "very different" efficacy or safety to displace the first mover.
• Combination Landscape: Anticipates a crowded field of novel combinations (PRMT5, PARP1, ADCs, EGFR bispecifics); selection of partners is driven by "in-lead" status of the partner compound (e.g., BMS Nevometastat).

Macro / Industry Outlook:

• Unmet Medical Need: Highlights that 85% of CRC cases are MSS (immune-unresponsive to standard checkpoint inhibitors) and pancreatic cancer has a 5-year overall survival of only ~5-10% for Stage IV, necessitating novel mechanisms.
• Mechanism Validation: Believes TGF-β blockade is critical for overcoming immune exclusion in liver metastases and MSS tumors, a specific niche not fully addressed by anti-PD-1 alone.
• Standard of Care Evolution: Expects chemotherapy to remain a backbone in first-line settings for the near future; targeted combinations (e.g., with PRMT5 inhibitors) may eventually displace chemo in selected populations, but chemo will persist in later lines.

Strategic Initiatives:

• Collaborations Announced:
  • INCB-734 + Nevelimetastat (BMS): PRMT5 inhibitor collaboration launched; BMS is in lead phase.
  • INCB-734 + SFV1521: PARP1 inhibitor collaboration.
  • INCB-734 + Pedocentamab (GenMab): EGFR-LGR5 bispecific collaboration launched, focusing on CRC; enrollment in head and neck/other areas possible.
  • INCB-890 + Next-Gen Anti-CTLA-4: Collaboration announced with a novel anti-CTLA-4 antibody.
  • INCB-890 + EGFR Antibody/ADC: Ongoing conversations for head and neck and lung cancer expansions; new ADC partner to be announced shortly.
• Clinical Trial Milestones:
  • NEXUS-0303 (890): Phase 3, N=700, frontline MSS CRC, comparing 890 + FOLFOX/Bev vs. placebo; hierarchical testing prioritizes PD-L1 positive subgroup.
  • DAWN-0303 (734): Phase 3, PDAC, comparing 734 + chemo (Gem/Abx or mFOLFIRINOX) vs. chemo + placebo; enrolling globally.
  • START (734): Phase 3, second/third-line KRAS G12D-mutant CRC, 734 + Cetuximab.
  • Adjuvant POC (890): ctDNA-positive post-surgery CRC, treating for up to 12 months; primary endpoint is ctDNA clearance.
  • Adjuvant (734): Phase 3 adjuvant PDAC study planned for 2027.
• Internal Development: All programs (890, 734, 667) discovered and developed internally; CSO Patrick Mace highlighted as leader.

Risks and Headwinds to Outlook:

• Safety Concerns:
  • INCB-890: Myocarditis observed in 4 patients (~1% incidence); management states this is consistent with background rates of PD-1 monotherapy and all cases resolved (asymptomatic).
  • INCB-734: GI toxicity (nausea/vomiting) and rash (in Cetuximab combo); management expects manageable profiles with proactive prophylaxis and training.
• Data Maturation: Current efficacy data (ORR, PFS) based on short follow-up (e.g., median ~6 months); durability and OS data will take 1–2 years to mature.
• Enrollment Risks: While enrollment is described as "accelerating," global enrollment in head-to-head settings with established chemo backbones presents execution risks.
• Competitive Risk: Multiple KRAS G12D programs and TGF-β bispecifics are advancing; success depends on demonstrating superior durability or specific population targeting (e.g., liver mets).
• Regulatory Uncertainty: Accelerated approval via ORR is possible but requires confirmatory OS/PFS data; final success hinges on statistical significance against historical benchmarks (e.g., doubling ORR, improving PFS from 5 to 8+ months in PDAC).

Management Tone on the Future:

• Confidence Level: High conviction and "very proud" of the internal discovery and Phase 3 readiness. Describes data as "de-risking" pivotal trials.
• Strategic Clarity: Firmly focused on GI oncology as the primary near-term franchise, with expansion to other solid tumors contingent on Phase 2 proof-of-concept.
• Hedges: Acknowledges that the "on-off" mechanism advantage over "on-only" competitors and the specific TGF-β microenvironment targeting require time to validate in final efficacy data (OS).
• Outlook: Emphasizes that the "game is durability" and that current early signals (high ORR, ctDNA clearance) provide a strong foundation for the upcoming Phase 3 reads.