GenFleet's October 2026 investor presentation reports clinical activity with the chemotherapy-free combination of GFH375 (KRAS G12D inhibitor) and cetuximab (EGFR antibody) in metastatic colorectal and pancreatic cancers, following earlier acceptance for full ESMO 2026 late-breaking abstract submission. Heavily pretreated mCRC (n=54): - ORR: 44% - DCR: 89% - Median PFS: 7.3 months (median follow-up 5.4 months) - 94% treated in third line or later - 50% treated in fourth line or later - 65% remained on treatment at data cutoff First-line KRAS G12D-mutant PDAC (n=24): - ORR: 71% - DCR: 100% - 88% remained on treatment - 96% had metastatic disease - Median follow-up: 3.8 months, with only three PFS events What cetuximab may add, monotherapy vs combination: Metastatic CRC (both previously treated): - ORR: 11% → 44% - DCR: 71% → 89% - Monotherapy n=28; combination n=54 PDAC (different treatment settings): - ORR: 40.7% → 71% - DCR: 96.7% → 100% - Monotherapy n=59 (previously treated); combination n=24 (first-line) The contribution of cetuximab is particularly interesting in CRC, where the combination's higher response rate may reflect suppression of adaptive EGFR signaling. In PDAC, differences in treatment line limit direct comparison. These are nonrandomized cohorts. Tolerability (n=78): - Grade 3 treatment-related adverse events: 24% - Treatment interruptions: 21% - Dose reductions: 5% - Treatment-related discontinuations: 0% - No Grade 4–5 treatment-related adverse events GI events were frequent, predominantly low-grade, with limited information on their evolution over successive treatment cycles. US experience with VS-7375 🇺🇸(the same molecule as GFH375 🇨🇳): GI adverse events are predominantly front-loaded, attenuating after the first cycle. Administration with food and prophylactic antiemetics have improved tolerability. An improved formulation is under development, with no vomiting observed in preliminary canine testing, aiming to further improve tolerability without compromising antitumor activity. Why chemotherapy-free treatment matters: real-world attrition and patient choice. Metastatic CRC, Danish nationwide registry (n=7,202): - 46.4% never initiated first-line systemic treatment - 47.6% of treated patients reached second line - 20.3% of treated patients reached third line Metastatic PDAC, 2026 US real-world analysis (n=2,708): - 35% received no systemic therapy - 52% of patients starting chemotherapy discontinued within 90 days - 34% of chemotherapy starters discontinued within 90 days without documented disease progression Metastatic PDAC, Netherlands nationwide study (n=13,756): - 72% received no systemic therapy - Patient or family preference accounted for 39% of reported reasons for withholding systemic treatment Daraxonrasib Phase III, RASolute 302: - 15.1% randomized to chemotherapy never initiated treatment - 2.8% randomized to daraxonrasib never initiated treatment The burden of chemotherapy is real. Patients can tolerate only so much treatment, and its physical and personal costs can limit what remains possible. The potential of chemotherapy-free regimens extends beyond avoiding cytotoxic therapy: durable disease control while preserving patient fitness, treatment continuity and future therapeutic options. @FAndreMD @EileenMOReilly @Aiims1742 @MPishvaian #KRAS #G12D #GFH375 #PDAC #ESMO26 📎 genfleet.com/Public/Uploads/…