Taiho Pharma R&D
Merck & Co. will partner with Taiho Pharmaceutical and Astex Pharmaceuticals, a wholly owned subsidiary of Otsuka Pharmaceutical, to develop small molecule inhibitors against the KRAS oncogene and several other drug targets under study as potential cancer treatments, through a collaboration that could generate more than $2.5 billion for Taiho and Astex. [Taiho Pharmaceutical]

Merck & Co. said today it will partner with Taiho Pharmaceutical and Astex Pharmaceuticals, a wholly-owned subsidiary of Otsuka Pharmaceutical, to develop small molecule inhibitors against the KRAS oncogene and several other drug targets under study as potential cancer treatments, through a collaboration that could generate more than $2.5 billion for Taiho and Astex.

Merck, Taiho, and Astex have agreed to combine preclinical candidates, as well as data and expertise from their respective research programs, through an exclusive global license granting Merck access to the small molecule inhibitor candidates of Taiho and Astex.

“This agreement with Taiho and Astex combines our respective small molecule assets and industry-leading expertise in cancer cell signaling to enable development of the most promising drug candidates,” Roger M. Perlmutter, MD, PhD, president, Merck Research Laboratories, said in a statement.

Merck said the collaboration was its latest demonstration of its commitment to exploring the potential of immuno-oncology—a commitment that has led to research across more than 30 tumor types.

In return, Merck agreed to pay Taiho and Astex an aggregate upfront payment of $50 million, plus up to approximately $2.5 billion tied to achieving preclinical, clinical, regulatory, and sales milestones for unspecified “multiple” products arising from the agreement, as well as tiered royalties on sales.

Merck also agreed to fund R&D for the collaboration, and to oversee commercialization of products globally—though Taiho has retained co-commercialization rights in Japan, as well as an option to promote in specific areas of South East Asia.

“This alliance builds on our KRAS research up to now and together with Merck, allows us to combine our expertise to significantly accelerate the global research, development, and commercialization of a number of our mutant KRAS programs by accessing external talent and resources,” added Teruhiro Utsugi, PhD, managing director at Taiho.

Until now, Merck has pursued a KRAS-targeting cancer treatment through a 50-50 global profit-sharing collaboration with Moderna to develop its KRAS cancer vaccine mRNA-5671, now under study in a Phase I trial (NCT03948763) in colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer.

KRAS has been a target of growing interest to several drug developers in recent months. In October, Amgen researchers published a study in Nature detailing their discovery of a small molecule inhibitor of KRASG12C, AMG 510, which is under study as a potential treatment for a variety of solid tumors with KRAS G12C mutation. According to Amgen, AMG 510 is the first investigational KRASG12C inhibitor to advance into clinical phases, and is now enrolling patients in a potentially registrational Phase II study (NCT03600883).

Also in October, Boehringer Ingelheim advanced its novel, oral inhibitor BI 1701963 into a Phase I clinical trial (NCT04111458), alone and in combination with Novartis’ Mekinist® (trametinib). BI 1701963 is a pan-KRAS inhibitor designed to target a broad range of oncogenic KRAS variants, including all major G12 and G13 oncoproteins. BI 1701963 was among candidates in Boehringer Ingelheim’s pan-KRAS program shown to generate positive preclinical data at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Other companies pursuing KRAS treatments:

  • Mirati Therapeutics, which in October reported that its KRAS G12C inhibitor MRTX849 demonstrated clinical activity, including objective responses, in patients with NSCLC and CRC.
  • Johnson & Johnson’s Janssen Biotech and Wellspring Biosciences, a wholly-owned subsidiary of Araxes Pharma, which in May 2019 announced FDA clearance for their IND application for ARS-3248, a small molecule KRAS G12C inhibitor. Janssen is conducting the Phase I trial and has sole responsibility for clinical development.
  • AstraZeneca, which in April 2019 ended development of AZD4785 (formerly IONIS-KRAS-2.5 Rx), licensed from Ionis Pharmaceuticals, following a Phase I study.

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