INCYTE INVESTOR EVENT AT ESMO 2026 - MORPHOSYS AG

Explicit Guidance:

• Top-line Data Timelines: Top-line data for the Phase 3 DAWN-303 study (734 in PDAC) expected in 2028; top-line data for the Phase 3 Nexera study (890 in MSS colorectal cancer) expected in 2029.
• Study Initiation Timelines: Phase 3 adjuvant study for 734 in pancreatic cancer (PDAC) planned to begin in 2027; Phase 3 pivotal study for 734 in second/third-line colorectal cancer planned to initiate in the first half of 2027.
• Enrollment Status: DAWN-303 (PDAC) and Nexera (CRC) are actively enrolling "very well" and "accelerating as we speak"; DAWN-303 accrual expected to complete rapidly.

Business-Segment Outlook:

• Program Expansion (734): Moving beyond first-line PDAC to adjuvant setting (curative intent) starting 2027; expanding into second/third-line colorectal cancer via pivotal trial starting H1 2027; pursuing first-line colorectal and other indications (NSCLC).
• Program Expansion (890): Shifting focus to frontline MSS colorectal cancer as lead indication with Phase 3 ongoing; initiating adjuvant proof-of-concept study for ctDNA-positive post-resection patients (primary endpoint: ctDNA clearance); expanding into head and neck cancer, ovarian cancer, and non-small cell lung cancer.
• Portfolio Strategy: Building a world-class solid tumor franchise centered on GI oncology (pancreatic and colorectal) while expanding into broader solid tumors; leveraging high-incidence indications addressing ~250,000 new patients annually.
• Commercial Focus: Targeting "largest patient benefit" and "largest commercial opportunity" by moving therapies to frontline and adjuvant settings where outcomes are historically poor.

Market and Competitive Outlook:

• Differentiation Strategy (734): Positioning as a "first mover" in KRAS G12D on-off inhibitors; claims "co-lead" status with comparable safety/efficacy to competitors but faster global enrollment; aiming to differentiate via superior durability and target coverage (IC95).
• Combination Landscape: Anticipating a "crowded space" with multiple KRAS G12D and PRMT5 inhibitors; differentiating through strategic partnerships (e.g., BMS for PRMT5, Genmab for EGFR-LGR5 bispecific) and data on synergy.
• Treatment Paradigm Shift: Expecting a potential future shift away from chemotherapy in first-line PDAC if non-chemo combinations (e.g., PRMT5) demonstrate sufficient response/durability, though chemotherapy remains standard for now.
• Bispecific Competition: Acknowledges a "race" among TGF-beta/PD-1 bispecifics in colorectal cancer but maintains that 890 has a distinct biological rationale targeting liver metastases (TGF-beta high/immune excluded).

Macro / Industry Outlook:

• Unmet Medical Need: Emphasizes the severity of current outcomes (e.g., <5% survival for stage 4 PDAC, negligible response to immunotherapy in MSS CRC) to justify the commercial and medical value of the pipeline.
• Regulatory Strategy: DAWN-303 designed with multiple primary endpoints (PFS, ORR, OS); potential for accelerated approval based on ORR if it meets criteria (e.g., doubling of historical response rates) with confirmatory OS/PFS data following.
• Global Development: Utilizing global enrollment for pivotal trials to accelerate timelines and ensure diverse patient populations.

Strategic Initiatives:

• Partnerships & Collaborations (734):
  • PRMT5: Collaboration with BMS (Nevolimstat) initiated; compound selected as it is already in pivotal trials.
  • PARP1: Collaboration with Symbio (SFV1521) announced.
  • EGFR: Collaboration with Genmab (Pedocentamab) launched for colorectal cancer.
  • Chemotherapy: Ongoing enrolling of cohorts with FOLFOX/FOLFIRI + Cetuximab for first-line colorectal.
• Partnerships & Collaborations (890):
  • CTLA-4: Collaboration with Next Generation (MASC-0303 antibody) announced.
  • EGFR: Conversation with an EGFR antibody partner ongoing; announcement expected within weeks.
  • ADC: Collaboration with a novel Antibody-Drug Conjugate (ADC) announced; details to follow shortly.
• Innovation: Developing "on-off" inhibitor mechanism for 734 to maximize KRAS inhibition; using a tissue-specific bispecific mechanism for 890 to avoid systemic toxicity associated with traditional TGF-beta inhibition.

Risks and Headwinds to Outlook:

• Data Maturity: Current efficacy data (response rates, PFS) are from Phase 1/early Phase 2 with short follow-up; durability of response (OS/PFS) requires further maturation (updates expected next year).
• Safety Profiles:
  • 890: Low incidence of myocarditis (~1%) observed, consistent with background rates for PD-1 inhibitors; no fatal events reported to date.
  • 734: Managing GI toxicity (nausea, vomiting, diarrhea) which is manageable but requires proactive patient training and anti-diarrheal/anti-emetic protocols.
• Competitive Dynamics: Potential for other KRAS G12D inhibitors or pan-RAS inhibitors to capture market share if they achieve earlier approval or superior efficacy.
• Regulatory Uncertainty: Accelerated approval strategies remain dependent on interim ORR data sufficiency; final confirmation of OS benefit is required for full approval.
• Biology: Uncertainty regarding the long-term efficacy of targeting TGF-beta in colorectal cancer compared to other bispecifics; potential for immune escape mechanisms to emerge.

Management Tone on the Future:

• High Confidence: Management expresses "high degree of conviction" that 890 and 734 will deliver positive trends and de-risk the pivotal trials.
• Strategic Pride: Emphasizes pride in discovering and developing both programs in-house; frames data as "substantially de-risking" the ongoing Phase 3 studies.
• Aggressive Pacing: Tone indicates a "fast-moving" organization, with plans to accelerate combinations and move into adjuvant settings quickly to capture commercial opportunity.
• Hedges: Carefully notes that "durability" is the ultimate measure of success for 890 and that "time will tell" on the on-off inhibitor advantage for 734.

Miscellaneous:

• Adjuvant Strategy: Strong belief that "greatest patient benefit" lies in earlier intervention (adjuvant settings); proof-of-concept study for 890 in ctDNA-positive colorectal patients already starting.
• Biomarker Focus: Using ctDNA clearance as a surrogate endpoint for disease-free survival in adjuvant 890 trials; tracking G12D allele VAF reduction as a correlate for response in 734 trials.
• Trial Design: DAWN-303 requires measurable disease by RECIST; Nexera (890) uses hierarchical testing prioritizing PD-L1 positive subgroups based on Phase 1 response data.