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The RAS pathway is one of the most frequently dysregulated signaling pathways in human cancers, with KRAS, NRAS, or HRAS gene mutations present in approximately 20% of cancers, among which KRAS mutations are the most common. Research data shows that over 70% of pancreatic cancer patients, over 40% of colorectal cancer patients, and approximately 11% of non-small cell lung cancer patients have KRAS gene mutations. Due to the lack of suitable binding sites on the RAS protein surface, targeting RAS mutation-driven tumors has always been a major challenge in drug development. Currently approved KRAS G12C inhibitors only target the KRAS G12C mutation in non-small cell lung cancer indications, while there is a lack of effective therapeutic drugs for more prevalent but harder-to-tackle mutation subtypes and their related multiple cancer types. There is an urgent clinical need for pan-RAS inhibitors that can broadly cover multiple RAS mutations, effectively overcome existing resistance mechanisms, and have anti-tumor activity across multiple cancer types. According to industry forecasts, the global RAS-targeted drug market is expected to grow continuously at a compound annual growth rate of approximately 12% over the next decade. 

AN9025 employs next-generation molecular glue technology, inducing the formation of ternary complexes with RAS proteins to systematically reduce RAS protein function or protein levels from the source, achieving systematic regulation of signaling output across the entire KRAS, NRAS, and HRAS family. Unlike traditional inhibitors that primarily rely on active site binding, this mechanism does not depend on a single mutation site, providing a higher resistance barrier, directly addressing the pain point of easy resistance development with current first-generation single-target RAS inhibitors, and demonstrating clear differentiated innovative properties, with the potential to further extend patient benefits. Preclinical data shows that AN9025 can effectively inhibit multiple RAS mutations and has demonstrated significant and durable tumor suppression effects in various models including lung cancer, pancreatic cancer, and colorectal cancer.

Currently, AN9025 has completed IND filings in both China and the United States and has received FDA approval for clinical trials in the U.S., with clinical trials soon to commence. According to the agreement, ASK will be responsible for the development, production, and commercialization of AN9025 in China, and will pay Adlai Nortye a upfront payment of 35 million RMB, development milestones of up to 470 million RMB, sales milestones of up to 1.128 billion RMB, and tiered royalties based on annual net sales in China.

Mr. Ma, CEO of ASK Pharm, stated: "We are very pleased to reach a strategic cooperation with Adlai Nortye on the pan-RAS inhibitor AN9025. This cooperation is not only an introduction at the single project level but also an important manifestation of the company's innovation strategy upgrade. The company has built a solid oncology product portfolio: Limertinib (third-generation EGFR inhibitor) has been commercialized, while self-developed ASKB589 (CLDN18.2-targeted drug) and ASKC202 (MET inhibitor) are both in Phase III clinical trials, expected to become important growth engines for the company's innovative development.The introduction of this pan-RAS(on) molecular glue project represents a key step forward as the company actively moves toward source innovation areas with higher technical barriers and greater long-term value, while maintaining the steady progress of existing advantageous pipelines. We look forward to working shoulder to shoulder with Adlai Nortye, fully leveraging each other's complementary advantages in research and development, clinical development, and industrialization, to accelerate the delivery of AN9025 to benefit patients in China and globally."

Mr. Lu, CEO of Adlai Nortye, stated: "We are very pleased to reach the strategic cooperation on AN9025 with ASK Pharm. AN9025 is a differentiated pan-RAS (ON) inhibitor with the potential to become a best-in-class product. This cooperation is an important milestone in advancing the clinical research of AN9025 and realizing its commercial value, fully demonstrating our core advantages in the RAS-targeted drug discovery platform. By integrating Adlai Nortye's capabilities with ASK Pharm's excellent experience in research advancement and commercialization in greater China, both parties will accelerate the provision of new treatment options for patients with RAS mutation-related tumors, addressing significant unmet clinical needs."

About RAS Mutation Tumors

The RAS pathway is one of the most frequently dysregulated signaling pathways in human cancers, with KRAS, NRAS, or HRAS gene mutations present in approximately 20% of cancers, among which KRAS mutations are the most common. KRAS mutations are present in 73.51% of pancreatic adenocarcinomas, 41.45% of colorectal cancers, and 11.24% of non-small cell lung cancers ^[1]. Due to the lack of suitable binding sites on the RAS protein surface, targeting RAS mutation-driven tumors has always been difficult. The discovery of the Switch-II pocket in 2013 promoted the development of KRAS inhibitors, particularly KRAS G12C inhibitors. However, currently approved KRAS G12C inhibitors only target KRAS G12C mutation non-small cell lung cancer indications, while common mutation types such as G12D, G12V, Q61H and their related other tumor types still lack effective drugs. The objective response rate of KRAS G12C inhibitors as monotherapy in second-line treatment of non-small cell lung cancer is only around 40%, with a median progression-free survival of approximately 5-6 months, and patients have limited treatment options after developing resistance. There is an urgent clinical need for pan-RAS inhibitors that can broadly cover multiple mutations, effectively overcome existing resistance, and have anti-tumor activity across multiple tumor types.

References

1.J Cancer Res Clin Oncol. 2025 Feb 27;151(2):94. doi: 10.1007/s00432-025-06118-9.

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