Bristol Myers Squibb Discontinues KRAS G12D Inhibitor MRTX1133 Development Following Unsatisfactory Pharmacokinetic and Clinical Data
Bristol-Myers Squibb
Biopharmaceutical and Nutritional Product R&D and Sales
On March 5, 2025, according to foreign media reports, Bristol-Myers Squibb (BMS) has abandoned the KRAS G12D inhibitor MRTX1133 project it previously acquired.
In the field of cancer treatment, KRAS G12D inhibitors have always been a research hotspot. KRAS G12D is a common mutation type in various cancers, especially in pancreatic cancer.Approximately 80% of patients have KRAS mutations, with the majority being G12D mutations. This makes KRAS G12D a highly promising therapeutic target in pancreatic cancer treatment.
MRTX1133, which was previously of interest to Bristol-Myers Squibb, is an effective, selective, and non-covalent KRAS G12D inhibitor currently in Phase I clinical trials.
On October 8, 2023, BMS and Mirati Therapeutics announced a merger agreement.BMS Acquires Mirati for $58.00 Per Share in Cash, with an Equity Value of Up to $4.8 Billion.In addition, Mirati shareholders will also receive a contingent value right (CVR), with the potential for an additional $12.00 in cash per share, representing a total value of approximately $1 billion.
Through this acquisition of Mirati Therapeutics, Bristol-Myers Squibb (BMS) aims to strengthen its oncology portfolio and expand its presence in late-stage KRAS programs. Mirati Therapeutics is a standout company in the KRAS field.Its developed KRAS G12C inhibitor, adagrasib (brand name Krazati), has attracted significant attention.
At the same time, Mirati also owns assets such as the early clinical stage KRAS G12D small molecule inhibitor MRTX1133, the selective SOS1 inhibitor MRTX0902, and the first-in-class MTA-cooperative PRMT5 inhibitor MRTX1719.
BMS's acquisition this time undoubtedly aims to leverage Mirati's research and development achievements to gain an edge in the highly competitive oncology drug market.Especially in the highly promising KRAS target track, gaining a share.
This time, the development project of the KRAS G12D inhibitor MRTX1133 has been abandoned. According to a spokesperson for BMS, an important reason is its pharmacokinetic data."Highly variable and less than ideal."
Taking MRTX1133 as an example, its oral bioavailability is extremely low. Although oral administration has been achieved through formulation methods, the improvement in bioavailability has been ineffective, leaving significant room for optimization. This is analogous to a car with an unstable power system, causing it to speed up and slow down during operation, unable to ensure stable and efficient performance.The absorption, distribution, metabolism, and excretion of the drug in the body were severely affected, significantly weakening its efficacy and making the project extremely challenging to progress in its development.
And the clinical research results also poured a "bucket of cold water." The G12D project data, originally expected to be released in the first half of 2024, did not arrive as scheduled. The Phase 1/2 study of MRTX1133 was quietly terminated after completing Phase 1 in January 2025. This situation fully demonstrates that the project encountered significant obstacles during the clinical research process and failed to achieve the expected outcomes.
In the highly competitive pharmaceutical R&D field, time is life, and every delay could give competitors a head start. Moreover, unsatisfactory clinical trial results also led to BMS losing confidence in the future prospects of the project, ultimately resulting in their decision to abandon it.
Notably, when BMS acquired Mirati, the key focus was onIt is actually the KRAS G12C inhibitor Krazati, while MRTX1133 is more of an additional gain brought under its wing.However, Krazati's performance in the market has been disappointing, with sales in 2024 reaching only $118 million, far below expectations.
This outcome led BMS to reassess its resource allocation strategy for KRAS-related projects, deciding to concentrate resources on the development of products with greater potential or strategic importance. Against this backdrop, the KRAS G12D project was abandoned, with resources being reallocated to support more promising research and development directions.
At the same time, the overall performance of the KRAS G12C inhibitor track has cast a shadow over the development prospects of KRAS-related targets.The sales of Amgen's Lumakras, one of the two marketed KRAS G12C inhibitors, fell short of Wall Street analysts' expectations and failed to pass the evaluation at the FDA's ODAC meeting; the monotherapy clinical trial data of Mirati's Adgrasib was not impressive, the progress of combination therapy was also unsatisfactory, and its marketing application was rejected by the EU.
These negative developments have raised deep concerns for BMS regarding the future market competitiveness and commercial prospects of the G12D project, which also targets the KRAS mutation. Amid increasingly fierce market competition and rising R&D risks, it is quite understandable that BMS chose to cut its losses in a timely manner by abandoning the KRAS G12D project to mitigate potential risks.
BMS Abandons KRAS G12D Project, Result of Multiple Factors
