MSD takes a $400m bite of SciBrunch's KRAS drug

MSD has signed a global license agreement for a KRAS G12D inhibitor from China's SciBrunch Therapeutics, paying $400 million upfront to claim a slice of what is becoming an increasingly crowded category.

The exclusive, global license to SPR2015, which is still in preclinical development, comes with development, commercialisation and other payments – across multiple indications – that could swell the value of the deal to $2.13 million.

The molecular glue drug targets KRAS G12D (ON) – which targets the active 'on' state of the KRAS protein, which acts as a molecular switch in cells. In the on position, it continually signals cells to proliferate and form tumours.

KRAS mutations occur in nearly a quarter of all human cancers, with G12D the most commonly encountered. At the moment, there are no approved therapies specifically targeting that mutation, as the only two KRAS inhibitors on the market – Amgen's Lumakras (sotorasib) and Bristol Myers Squibb's Krazati (adagrasib) – both target the less common G12C mutation in its inactive off state.

Shanghai-based SciBrunch said the deal with MSD – known as Merck & Co in the US and Canada – validates its drug discovery platform and the potential of SPR2015 in "addressing longstanding unmet medical needs in oncology."

The company reported studies at this year's American Association of Cancer Research (AACR) congress which showed antitumour efficacy for SPR2015 as a monotherapy across multiple in vivo cell-derived and patient-derived xenograft models.

"Evidence continues to accumulate for the therapeutic potential of targeting the KRAS pathway, a well-characterised factor in tumour cell growth," said George Addona, head of discovery, preclinical development and translational medicine at Merck Research Laboratories.

"This agreement complements and diversifies our expanding pipeline of precision targeted candidates," he added.

KRAS G12D mutations are found in 37% of pancreatic ductal adenocarcinoma (PDAC) cancers, 13% of colorectal cancer cases, and 4% of non-small cell lung cancer (NSCLC) cases.

Other KRAS G12D (ON) inhibitors coming through clinical development include Revolution Medicines' daraxonrasib (phase 3) and zoldonrasib (phase 1/2) and Verastem Oncology's VS-7375 (phase 1). Meanwhile, there is a large and growing pipeline of other KRAS G12D-targeted drugs, such as GenFleet/Astellas' setidgrasib (phase 3), Incyte's INCB161734 (phase 3), Jiangsu Hengrui's HRS-4642 (phase 1/2), and Eli Lilly's LY3962673 (phase 1).