KENILWORTH, N.J.—Less than a week into the new year, what could be a contender for one of the largest deal values of 2020 has been announced: a $2.5-billion exclusive worldwide research collaboration and license agreement between Merck (known as MSD outside the United States and Canada), Taiho Pharmaceutical Co. Ltd. and Astex Pharmaceuticals, a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd. The companies will advance the development of small-molecule inhibitors against a number of drug targets for cancer treatment, including the KRAS oncogene.
“Taiho has used its unique and proprietary drug discovery platform to generate a number of small molecule inhibitors,” Dr. Teruhiro Utsugi, managing director at Taiho, said in a press release. “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.”
Per the terms of the agreement, the three collaborators will combine preclinical candidates and data with their respective expertise to develop promising compounds. Merck will be granted an exclusive global license to Taiho and Astex's small-molecule inhibitor candidates, for which the latter two companies will receive an aggregate upfront payment of $50 million, with the potential for up to approximately $2.5 billion in preclinical, clinical, regulatory and sales milestones. Taiho and Astex also stand to receive tiered royalties on sales of any products resulting from this deal. Merck will fun research and development, and will also assume responsibility for global commercialization of any products. Taiho retains co-commercialization rights in Japan and holds an option to promote in agreed-upon areas of Southeast Asia.
“Together with our Taiho colleagues, we are delighted to be working with Merck, one of the global leaders in oncology drug development, on this strategic alliance. This collaboration is another testament to Astex’s position as the leader in fragment-based drug discovery,” remarked Dr. Harren Jhoti, president and CEO of Astex.
Dr. Roger M. Perlmutter, president of Merck Research Laboratories, added: “At Merck we continue to pursue new regimens designed to extend the benefits of highly selective therapies to more patients with cancer. 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.”
Taiho's pipeline includes a number of compounds aimed against different types of cancer, including gastric, prostate, non-small cell lung, ovarian cancer and solid tumors. Astex's candidates range between Phase 1 and Phase 3 development in indications such as hematological malignancies, lymphomas and solid tumors.
KRAS is one of the most commonly mutated oncogenes in cancer, and is implicated in more than 90 percent of pancreatic cancers and roughly 20 percent of non-small cell lung cancers. According to the Genetics Home Reference site of the U.S. National Library of Medicine, part of the National Institutes of Health, the KRAS gene is part of the RAS/MAPK signaling pathway, and plays a role in cell division, differentiation and apoptosis.
The same day as the collaboration was announced, Merck also shared news that Keytruda plus chemotherapy had reached one of the dual primary endpoints of progression-free survival in the Phase 3 KEYNOTE-604 trial. The study is evaluating this combination regimen as a first-line treatment for patients with extensive-stage small cell lung cancer. Keytruda combined with either cisplatin or carboplatin led to a statistically significant improvement in progression-free survival compared to chemotherapy alone, and while statistical significance was not reached, it also resulted in an improvement in overall survival compared to chemotherapy alone.
“Results of KEYNOTE-604 demonstrated the potential of Keytruda, in combination with chemotherapy, to improve outcomes for patients newly diagnosed with extensive-stage small cell lung cancer, a highly aggressive malignancy,” commented Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We sincerely thank the patients and investigators for their participation in this study, and are committed to helping patients who face difficult-to-treat types of lung cancer.”