China Merchants Securities: The RAS circuit will lead to a real inflection point and a shift in core values in the field in the next three years

The Zhitong Finance App learned that China Merchants Securities released a research report saying that the RAS circuit has led to a real inflection point, focusing on “proven global benchmarks, Chinese assets that have reached the critical point of registration, and biomarker driven joint increments.” On a global level, Revmed has established clinical benchmarks in the field of Pan-RAS (ON) with Daraxonrasib's clinical phase III survival benefits in second-line MPDAC, and is accelerating expansion into first-line PDAC, perioperative period, and NSCLC; at the Chinese level, registration research promotion of HRS-4642 and GFH375 forms a recent value anchor, and GFH276, JAB-23E73, and other new Pan-RAS/Pan-KRAS mechanism assets provide medium- to long-term valuation flexibility. The bank believes that the core value transition in the RAS field in the next three years will first come from the confirmation of the expansion of second-line PDAC monotherapy to first-line and early-stage diseases, registration and implementation of G12D assets, and continuous optimization of the broad-spectrum inhibitor treatment window; the MTAP deficiency-PRMT5 synthetic lethal combination will provide additional upward space for RAS inhibitors to a precise joint backbone upgrade.

The main views of China Merchants Securities are as follows:

From “drugable” to “transformable survival”: the RAS circuit ushered in a real clinical inflection point

RAS was once regarded as an “untreatable” target due to the lack of traditional small molecule binding pockets on the surface. The first KRASG12C inhibitor was approved in 2021, completing a breakthrough in direct RAS inhibition from 0 to 1; in 2026, RevMed's daraxonrasib achieved MOS 13.2 months in RASG12 mutation second-line MPDAC clinical phase III Rasolute 302, nearly doubling that of 6.6 months (HR = 0.40), and simultaneously obtained significant improvements in PFS and ORR. This result indicates that the value judgment in the RAS field has been upgraded from “can inhibit a certain mutation” to “can bring significant survival benefits in tumors that are highly dependent on RAS”, and that broad-spectrum RAS (ON) inhibition has moved from mechanism innovation to clinical confirmation.

PDAC is the first core market to be realized. Competition will form a multi-layer ecosystem based on mutations, tumor types, and number of lines

More than 90% of patients in PDAC carry KRAS mutations, and non-G12C subtypes such as G12D, G12V, and G12R account for the vast majority, forming the patient base for broad-spectrum RAS suppression and accurate G12D suppression. Daraxonrasib has confirmed survival benefits in second-tier PDAC. Subsequent competition will accelerate progress to first-line, perioperative, and joint programs; G12D will become the most attractive segment for first-line pancreatic cancer. It is worth noting that MTAP deficiency provides the first accurate combination direction for RAS inhibitors with high clinical remission verification: vopimetostat forms dual biomarker synergy with RAS (ON) inhibitors by using mTAP deficient tumors on PRMT5; it is used in combination with daraxonrasib to obtain 92% ORR and 90% 6-month PFS rate in treating MTAP deficiency and RAS mutant PDAC, indicating that PDAC treatment is expected to be further upgraded from “broad-coverage RAS targeting” to “molecular fraction” Deep relief underneath the layer”.

China has become the second pole of RAS innovation in the world, and clinical progress and mechanism innovation are accelerating at the same time

Chinese companies have completed the first phase of commercialization of G12C and have shown stronger global competitiveness in next-generation assets: Jingfang GFH375 was the first to enter clinical phase III of oral G12D inhibitors and laid out Pan-ras (ON) molecular gel through GFH276; Gacos JAB-23E73 promoted global development with a pan-KRASON/OFF bipolar mechanism and obtained AstraZeneca authorization and verification; Hengrui used HRS-4642 first-line G12D mutation PDAC to advance phase III research and form G12D, G12C, and G12C Pan-RAS and Pan-Kras full path matrices. Pharma such as Betta and Baekje also continues to enrich the supply through Pan-RAS molecular gum, KRAS degradation, and brain penetrating RAS (ON) inhibitors. From the second half of 2026 to 2028, key data on G12D, Pan-RAS, and first-line PDAC will be read intensively, and Chinese assets are expected to continue to contribute to clinical catalysis and valuation revaluation of the global RAS circuit.

Risk warning: New drug development falls short of expectations, policy risks, etc.