INCYTE INVESTOR EVENT AT ESMO 2026 - MORPHOSYS AG

Explicit Guidance:

• Nex-3303 (890) Phase 3: Top-line data expected in 2029 for the NICS-0303 study (Folfox-Bev + 890 vs. placebo) in first-line MSS colorectal cancer; study size N=700, primary endpoint Progression-Free Survival (PFS).
• 734 Pancreatic (DAWN-303) Phase 3: Top-line data expected in 2028 for the DAWN-303 study (734 + chemo vs. placebo) in KRAS G12D-mutated PDAC; primary endpoints include Overall Survival (OS), PFS, and ORR.
• 734 Colorectal (START) Phase 3: Pivotal trial initiation planned for the first half of 2027 for second/third-line KRAS G12D-mutated colorectal cancer (734 + Cetuximab vs. chemo/Cetuximab); primary endpoint PFS.
• 734 Adjuvant PDAC: Phase 3 adjuvant study initiation planned for 2027, combining 734 with chemotherapy for curative intent.
• 890 Adjuvant CRC: Proof-of-concept study (ctDNA-driven) already underway; treats ctDNA-positive patients post-curative resection for up to 12 months.

Business-Segment Outlook:

• Program Expansion (890): Moving from first-line MSS colorectal cancer into adjuvant settings for ctDNA-positive Stage II/III patients (primary endpoint: ctDNA clearance at 3 months). Expansion into ovarian cancer, head and neck cancer, and non-small cell lung cancer is planned for early next year.
• Program Expansion (734): Lead indication is KRAS G12D-mutated pancreatic cancer; expansion into colorectal cancer (pivotal in 2027) and lung cancer is anticipated.
• Franchise Strategy: Building a world-class solid tumor franchise with a focus on gastrointestinal (GI) oncology, aiming to address ~250,000 new patients annually across colorectal, pancreatic, and ovarian indications.
• Commercial Goal: Targeting "frontline" interventions to capture the largest patient benefit and commercial opportunity, rather than late-line settings.

Market and Competitive Outlook:

• Competitive Positioning: Management views the 734 pancreatic program as a "co-lead" in the KRAS G12D space, noting comparable efficacy and safety to competitors (e.g., mirvetuximab/sotigalimab context implied) but highlighting faster enrollment and the "on-off" inhibitor mechanism which may offer more durable efficacy.
• Differentiation (890): The bispecific mechanism (TGF-beta R2 x PD-1) is positioned to overcome resistance to standard PD-1 inhibitors, specifically targeting the "immune-excluded" phenotype common in liver metastases and MSS colorectal cancer, a gap where prior TGF-beta inhibitors failed due to toxicity.
• Market Share: Anticipates a shift in treatment paradigms for KRAS G12D tumors, potentially displacing chemotherapy in the future if targeted combinations prove superior, though chemotherapy is expected to remain standard of care for the near term.
• First-Mover Advantage: Management believes early approval provides an advantage in clinical workflow adoption and physician familiarity, particularly regarding toxicity management (e.g., GI side effects) for KRAS inhibitors.

Macro / Industry Outlook:

• Clinical Standards: Current first-line benchmarks for MSS colorectal cancer remain FOLFOX+Bev (ORR ~45-50%, PFS ~10 months); 734 in PDAC currently benchmarks against Gem/Abx or mFOLFIRINOX (ORR 20-30%, PFS ~5-6 months).
• Evolving Landscape: Acknowledges a "crowded space" with multiple bispecifics and G12D inhibitors in development; expects data maturity in 2027-2029 to clarify the optimal combination partners and treatment sequences.
• Regulatory Strategy: Designed for potential accelerated approval pathways using ORR and PFS, with OS confirmatory data built into ongoing trials.

Strategic Initiatives:

• Partnerships (734): Launched collaborations with:
  • BMS: For Nevelimetastat (PRMT5 inhibitor).
  • Novartis: For PARP1 inhibitor (SFV1521).
  • GenMab: For Pedocentamab (EGFR-LGR5 bispecific), focusing on colorectal cancer, with decisions on first-line regimens to be data-driven.
• Partnerships (890): Collaboration announced with Next Generation for anti-CTLA-4 antibody; conversations ongoing for EGFR antibody and novel ADC partnerships.
• Pipeline Expansion: Initiating head-to-head and combination trials for 734 with Cetuximab, FOLFIRI, and FOLFOX; exploring 890 in ovarian, head and neck, and lung cancer.

Risks and Headwinds to Outlook:

• Data Maturity: Current efficacy data (e.g., ORR, PFS) relies on short-term follow-up (e.g., 6-month landmark for 890, early PFS for 734); durability and OS data are pending in 2027-2029.
• Safety Signals: Monitoring of rare adverse events; noted 4 cases of asymptomatic myocarditis in ~385 patients on 890 (incidence <1%), considered consistent with general PD-1 background risk.
• Toxicity Management: GI toxicities (nausea, vomiting, diarrhea) are manageable but require proactive patient education and dose adjustments; potential for reduced chemotherapy relative dose intensity.
• Competitive Dynamics: Risk of being "beaten" to market if competitors accelerate approval or demonstrate superior data; uncertainty regarding the ultimate role of chemotherapy in future first-line regimens.
• Enrollment/Execution: Reliance on fast enrollment in global Phase 3 trials to meet 2027-2029 milestones.

Management Tone on the Future:

• Confidence: High conviction regarding the potential of the franchise, citing "de-risked" pivotal trials and data "substantially" exceeding historical benchmarks (e.g., 83% ORR in liver mets for 890, 69-89% ORR for 734).
• Differentiation: Strong emphasis on the unique "on-off" inhibitor mechanism for 734 and the targeted delivery of the 890 bispecific to spare normal tissue as key differentiators from the competition.
• Speed: Aggressive pace with multiple Phase 3 trials running concurrently; "well underway" enrollment and accelerating timelines for adjuvant studies.
• Self-Reliance: Pride in the team's internal discovery and development capabilities (all programs discovered/developed in-house).

Miscellaneous:

• Pricing/Costs: No specific financial guidance (revenue, earnings, capex) provided in the transcript; focus is strictly on clinical milestones and development strategy.
• Specific Metrics:
  • 890 (CRC First-line): ORR 71% (83% in liver mets); 6-month PFS 81%; Disease Control Rate 100%.
  • 734 (PDAC First-line): ORR 69% (Gem/Abx) and 89% (mFOLFIRINOX); 6-month PFS 80-90%; Median Dose Intensity 67-69%.
  • 734 (CRC Second/Third-line): ORR 36% (with Cetuximab vs. <5% standard); Median PFS 7.2 months.