In a deal that could potentially be worth up to $1.2 billion, Astellas Pharma is teaming up with drug discovery firm Proteostasis Therapeutics to research and develop therapeutic candidates that modulate the unfolded protein response (UPR) through the use of Proteostasis' Disease Relevant Translation (DRT™) and Proteostasis Network platform. Astellas is giving Proteostasis an initial upfront payment along with a securities investment. Proteostasis is also eligible for research funding support and future milestones that the firm says could result in total payments of over $400 million as well as tiered royalties. Astellas can also begin two additional projects under the same terms.
Per the agreement, the two companies will conduct discovery, screening, and preclinical research to identify lead compounds for clinical development. Proteostasis will have the rights to opt in for global codevelopment and U.S. copromotion once candidates for further development are selected.
The firms say this worldwide collaboration will focus on one genetic disease and explore additional indications that can be affected through modulation of the UPR pathway. Many genetic diseases, neurodegenerative diseases, and retinal degenerative diseases are protein conformational diseases, where stress induced by accumulation of unfolded proteins in the endoplasmic reticulum has been observed. Selective modulation of the UPR pathway in nonclinical investigations, the companies say, improved stress response and restored function.
“Our novel approach to drug discovery, coupled with Astellas' track record in drug development, will enable rapid discovery and development of therapies for important unmet medical needs,” Meenu Chhabra, Proteostasis' president and CEO, said in a statement.
Astellas is also entering a three-year collaboration with the Dana-Farber Cancer Institute to research and develop small molecule inhibitors of the hard-to-target oncogene K-Ras for the treatment of cancer, including lung cancer. Astellas will provide support for the research and has an option to obtain an exclusive, worldwide license from Dana-Farber to any novel K-Ras inhibitors obtained from the collaboration; should they choose to exercise it, the Japanese firm could conduct further preclinical R&D on those K-Ras inhibitors as well as subsequent clinical development and commercialization.
The research will be led by Nathanael Gray, Ph.D., of the Cancer Biology Department at Dana-Farber and professor at Harvard Medical School, who, along with fellow investigators at Dana-Farber, has been researching new approaches to developing K-Ras inhibitors. “We are excited to work with a top-tier pharmaceutical company committed to innovative oncology research on this collaboration, and to develop novel inhibitors to this molecular target that have thus far been inaccessible,” Dr. Gray commented.