CMSC: The RAS track ushers in a genuine turning point, with a leap in core value in the field over the next three years.

CMSC released a research report stating that the RAS sector is reaching a significant turning point, focusing on "validated global benchmarks, Chinese assets entering the registration critical point, and biomarker-driven combined increments." From a global perspective, RevMed has established a clinical benchmark in the pan-RAS(ON) field with the survival benefits of daraxonrasib in the Phase III clinical trial for second-line mPDAC and is accelerating its expansion into first-line PDAC, perioperative settings, and NSCLC. From a Chinese perspective, the advancement of registration studies for HRS-4642 and GFH375 represents a recent value anchor, while assets such as GFH276, JAB-23E73, and other new mechanism pan-RAS/pan-KRAS assets provide medium- to long-term valuation flexibility. The firm believes that the core value leap in the RAS field over the next three years will primarily stem from the single-agent confirmation in second-line PDAC expanding to first-line and early stage diseases, the registration fruition of G12D assets, and the ongoing optimization of the therapeutic window for broad-spectrum inhibitors; the MTAP deletionPRMT5 synthetic lethality combination will provide additional upward space for RAS inhibitors to upgrade to precision combination backbones. CMSC's main points are as follows: From "druggable" to "survival-altering": The RAS pathway is welcoming a genuine clinical turning point. RAS has long been seen as an undruggable target due to the lack of traditional small molecule binding pockets on its surface. The approval of the first KRASG12C inhibitor in 2021 marked a breakthrough, achieving a direct inhibition of RAS from 0 to 1; in 2026, RevMed's daraxonrasib demonstrated a median overall survival (mOS) of 13.2 months in the Phase III clinical trial RASolute 302 for second-line mPDAC with RASG12 mutationsalmost doubling that of the chemotherapy group at 6.6 months (HR=0.40)while simultaneously achieving significant improvements in PFS and ORR. This result signifies a shift in the RAS field's value judgment from "Can we inhibit a certain mutation?" to "Can we bring significant survival benefits in RAS-dependent tumors?" The broad-spectrum RAS(ON) inhibition is transitioning from mechanistic innovation to clinical confirmation. PDAC is the first core market to realize this potential, as competition will form a multi-layered ecosystem based on mutations, tumor types, lines of therapy, and combination therapies. Over 90% of patients with PDAC carry KRAS mutations, and non-G12C subtypes such as G12D, G12V, and G12R constitute the vast majority, forming the patient base for broad-spectrum RAS inhibition and G12D precision inhibition. Daraxonrasib has completed survival benefit confirmation in second-line PDAC, and subsequent competition will accelerate towards first-line, perioperative settings, and combination regimens; G12D is becoming the most attractive sub-sector in first-line pancreatic cancer. Notably, MTAP deletion offers the first clinically validated precision combination direction for RAS inhibitors: vopimetostat leverages the dependency of MTAP-deleted tumors on the synthetic lethality target PRMT5, creating a dual biomarker synergy with RAS(ON) inhibitors; its combination with daraxonrasib achieved a 92% ORR and a 90% six-month PFS rate in treated patients with MTAP deletion and RAS mutations, indicating that PDAC treatment is poised for advancement from "broad coverage of RAS targeting" to "deep remission under molecular stratification." China has emerged as the second hub for global RAS innovation, with clinical progress accelerating alongside mechanistic innovation. Chinese companies have completed the first phase of G12C commercialization and demonstrated stronger global competitiveness in next-generation assets: Jingfang's GFH375 has entered Phase III clinical trials for oral G12D inhibitors, and GFH276 is positioned as a pan-RAS(ON) molecular glue; JAKS' JAB-23E73 is advancing global development with a pan-KRAS ON/OFF dual-mode mechanism, validated through licensing with AstraZeneca; Heng Rui is driving Phase III research on first-line G12D mutation PDAC with HRS-4642, forming a comprehensive matrix of G12D, G12C, pan-RAS, and pan-KRAS pathways. Companies like Betta and BeiGene are also continuously enhancing supply through pan-RAS molecular glues, KRAS degradation, and blood-brain barrier-penetrating RAS(ON) inhibitors. From the second half of 2026 to 2028, key data on G12D, pan-RAS, and first-line PDAC will be released intensively, with Chinese assets expected to continuously contribute to clinical catalysts and valuation re-evaluations in the global RAS sector. Risk reminders: Risks associated with new drug development not meeting expectations, policy risks, etc.