Merck Licenses SciBrunch's Preclinical Oral KRAS G12D Inhibitor SPR2015 in $2.13 Billion Deal
核心洞察
Merck (搜索) has secured exclusive worldwide rights to SPR2015 (搜索), a preclinical oral KRAS G12D (搜索) (ON) inhibitor from Shanghai-based SciBrunch Therapeutics (搜索), in a deal announced September 28, 2026.
SciBrunch receives a $400 million upfront payment and is eligible for development, regulatory and commercial milestones that could bring the total transaction value to $2.13 billion.
SPR2015 (搜索) is a molecular glue inhibitor that showed nanomolar antiproliferative activity in KRAS G12D (搜索)-mutant cell lines with selectivity over KRAS wild-type cells, plus monotherapy antitumor activity in xenograft models.
Merck (搜索) has entered an exclusive global license agreement with Shanghai-based SciBrunch Therapeutics (搜索) for SPR2015 (搜索), an investigational preclinical oral KRAS G12D (搜索) (ON) inhibitor, the companies announced on September 28, 2026. The deal gives Merck worldwide rights to develop, manufacture and commercialize the compound, with a total potential value of $2.13 billion.
Under the terms, SciBrunch receives a $400 million upfront payment and is eligible for milestone payments tied to development, commercialization and other activities across multiple indications. Merck (搜索) said the transaction has closed and that it will record a pre-tax charge of $400 million, or approximately $0.13 per share, in its third-quarter 2026 GAAP and non-GAAP results. BofA Securities acted as exclusive financial advisor to SciBrunch.
A Molecular Glue Aimed at the Active Form of KRAS G12D
SPR2015 (搜索) is described by Merck (搜索) as a potent and selective molecular glue KRAS G12D (搜索) (ON) inhibitor. It has demonstrated nanomolar antiproliferative activity across a range of KRAS G12D-mutant cell lines while maintaining selectivity over KRAS wild-type cells, a distinction relevant for a drug intended to act on tumor cells without excessive off-target effects.
In preclinical testing, SPR2015 (搜索) showed antitumor efficacy as a monotherapy across multiple in vivo cell-derived and patient-derived xenograft (CDX/PDX) models, according to preclinical data presented at the 2026 AACR Annual Meeting. The compound remains in preclinical development, and the September 28 announcement provided no human efficacy or safety results, did not identify the first cancer indication Merck (搜索) will pursue, and set no first-in-human trial date.
Why KRAS G12D Matters
KRAS G12D (搜索) is the most common oncogenic RAS mutation in human tumors. It results from substitution of glycine with aspartate at position 12, a change that leaves KRAS active and continuously signaling for cell proliferation and survival. The mutation is prevalent in pancreatic cancer (搜索), colorectal cancer (搜索) and non-small cell lung cancer (搜索), among other solid tumors.
KRAS mutations rank among the most frequent genetic drivers of human cancer, but the protein was long considered difficult to drug because of its smooth surface and lack of an obvious binding pocket. That changed with targeted therapies against KRAS G12C, which reached clinical use in recent years. G12D remains a distinct and more prevalent target, and a validated oral inhibitor for this subtype would fill a significant gap in precision oncology.
Merck (搜索) already has a KRAS drug in the clinic: the KRAS G12C inhibitor calderasib (搜索), which is in phase 3 trials for colorectal cancer (搜索) and non-small cell lung cancer (搜索). The SciBrunch agreement adds a KRAS G12D (搜索) bet to that pipeline.
Company Commentary
"Evidence continues to accumulate for the therapeutic potential of targeting the KRAS pathway, a well-characterized factor in tumor cell growth," said George Addona, senior vice president, discovery, preclinical development and translational medicine, Merck (搜索) Research Laboratories. "This agreement complements and diversifies our expanding pipeline of precision targeted candidates with SPR2015 (搜索), a potent engineered inhibitor for one of the most prevalent mutant forms of KRAS found in human cancers."
Tao Hu, founder, chairman and chief executive officer of SciBrunch, said the company has focused since its founding on advancing therapies targeting the RAS pathway and on delivering treatment options for patients with pancreatic, colorectal, lung and other major malignant tumors. "This agreement with Merck (搜索) not only validates the R&D strength of our platform but also underscores the potential of SPR2015 (搜索) in addressing longstanding unmet medical needs in oncology," Hu said.
SciBrunch's Profile and the Competitive Landscape
SciBrunch Therapeutics (搜索) was founded in late 2024 and is headquartered in Shanghai. The clinical-stage biotech focuses on small-molecule oncology therapeutics and was co-founded by Tao Hu alongside medicinal chemist Yang Zhang. The company has taken a lead candidate, a brain-penetrant PARP1 selective inhibitor for a range of cancers, into the clinic, supported by $65 million raised across two funding rounds.
Other groups are pursuing the same mutation. Revolution Medicines said on June 23 that it had begun treating patients in a phase 3 trial of zoldonrasib, a covalent RAS(ON) G12D inhibitor, in RAS G12D-mutant metastatic pancreatic cancer (搜索), testing the oral drug with chemotherapy as a first-line treatment. That randomized trial compares zoldonrasib plus investigator-selected chemotherapy with placebo plus chemotherapy, with progression-free survival and overall survival as primary endpoints. Revolution estimates RAS G12D occurs in about 40 percent of pancreatic ductal adenocarcinoma cases, while Fierce Biotech reported the mutation is found in about 38 percent of pancreatic cancer patients. Bayer (搜索) has also signed a $1.3 billion biobucks deal with Kumquat Biosciences (搜索) for a preclinical asset in this space.
Merck (搜索) said it plans to advance SPR2015 (搜索) using its global oncology development infrastructure. The program remains early stage, and substantial testing lies ahead before its safety and efficacy in humans are established.