Merck & Co. is expanding its presence in the increasingly competitive KRAS G12D field, agreeing to pay China-based SciBrunch Therapeutics $400 million upfront for rights to a preclinical drug candidate.
The therapy, known as SPR2015, will be licensed to Merck on a worldwide basis. The agreement also includes development and other milestone payments that could push the total deal value to as much as $2.13 billion across multiple potential indications.
KRAS is among the most frequently altered oncogenes, but for many years researchers struggled to develop medicines against it because the protein lacked obvious binding sites that could be exploited by conventional drugs. That landscape began to change after Amgen and Mirati Therapeutics demonstrated that KRAS G12C could be successfully targeted with Lumakras and Krazati, respectively, prompting drugmakers to pursue additional KRAS variants.
KRAS G12D has emerged as one of the leading targets in the next generation of KRAS drug development. The mutation occurs in roughly 40% of pancreatic cancer cases, according to cited research, creating a substantial potential patient population.
Several major drugmakers are now pursuing the target. Bayer, for example, previously entered a potential $1.3 billion collaboration with Kumquat Biosciences involving a preclinical KRAS G12D candidate.
Merck already has a KRAS program in clinical development through calderasib, an inhibitor of KRAS G12C that is being evaluated in Phase 3 studies for colorectal cancer and non-small cell lung cancer. The SciBrunch agreement gives the company an additional program aimed at the G12D mutation.
George Addona, SVP of Discovery, Preclinical Development and Translational Medicine at Merck Research Laboratories, said the growing body of evidence supporting KRAS pathway inhibition reinforces the therapeutic potential of targeting a pathway known to play a central role in tumor growth.
He added that SPR2015 broadens Merck’s precision-medicine pipeline by introducing an engineered inhibitor directed against one of the most prevalent mutant KRAS forms found in human cancers.
According to Merck, preclinical testing has shown that SPR2015 can inhibit the proliferation of several KRAS G12D-mutant cell lines at nanomolar concentrations while retaining strong selectivity against cells carrying normal KRAS.
SciBrunch, which is headquartered in Shanghai, was founded two years ago by entrepreneur Tao Hu and medicinal chemist Yang Zhang. The biotech has already advanced its lead program, a brain-penetrating PARP1-selective inhibitor intended for several types of cancer, into clinical testing.
The company has raised $65 million through two financing rounds to support its pipeline. Hu said SciBrunch has focused since its establishment on developing therapies against the RAS signaling pathway and aims to produce new treatment options for people with major cancers, including pancreatic, colorectal and lung tumors.
It has been a positive week for Merck. A few days ago, the company said that its experimental injectable treatment for diabetic macular edema delivered visual-acuity improvements comparable to the current standard therapy in a clinical study involving people with diabetes.
The 52-week study enrolled 984 patients suffering from the disease, and the experimental treatment’s results were found comparable to Roche’s Ranibizumab for average change from baseline.
Merck has entered into an exclusive global licensing agreement with China-based SciBrunch Therapeutics for SPR2015, an investigational oral KRAS G12D inhibitor. The agreement gives Merck worldwide rights to develop, manufacture, and commercialize the preclinical cancer treatment.
Under the agreement, SciBrunch will receive $400 million upfront, while additional development and commercialization milestones could bring the total potential value of the transaction to $2.13 billion. The deal has already closed.
v and the KRAS G12D Opportunity
SPR2015 is designed to target the active, or “ON,” form of KRAS G12D. The mutation is an important cancer-driving alteration found across several solid tumors, including pancreatic, colorectal, and lung cancers.
SciBrunch and the Future of KRAS G12D Development
KRAS G12D has become an important target in oncology drug development because of its role in multiple cancers. The SciBrunch agreement demonstrates continued pharmaceutical investment in approaches designed to selectively inhibit this mutation.
