The focus will be on discovering drugs that use the body’s natural protein control processes. Proteins that are mutated or dysregulated play an important role in many diseases. Nurix’s technology platform manipulates the ubiquitin system and its component E3 ligases, the enzymes that control protein levels in human cells.
Under the deal, Gilead will pay Nurix $45 million upfront. Nurix will be eligible for up to $2.3 billion in milestone payments as well as up to low double-digit tiered royalties on net sales. For any programs that Nurix chooses to co-develop and co-detail, the two companies will split development costs in addition to profits and losses 50/50 for the U.S. market. Nurix will be eligible for royalties on sales outside the U.S. and reduced milestone payments.
Nurix will use it drug discovery platform to identify compounds that utilize E3 ligases to stimulate degradation of specified drug targets. Gilead has the option to license drug candidates directed to up to five targets coming out of the work. Nurix will have the option to co-develop and co-detail up to two programs in the U.S. The agreement does not include Nurix’s lead degradation program.
“There are many molecular targets involved in disease pathways that have traditionally been challenging to manipulate using conventional approaches,” stated John McHutchison, Gilead’s chief scientific officer and Head of Research and Development. “Nurix’s innovative protein degradation discovery technology provides Gilead with a new strategy to interrogate these drug targets, as we continue to build a pipeline of small molecule therapeutics for patients with cancers and other diseases.”
“The field is primed to discover new drugs” Alessio Ciulli, a professor at Scotland’s University of Dundee, told BioWorld. Ciulli’s work is on PROTC (PROteolysis Targeting Chimeric ) molecules, which harnesses the ubiquitin-proteasome system that is adjacent to Nurix’s technology. Ciulli has also worked with Nurix. He told BioWorld that theoretically, these approaches are disease agnostic. “That’s the really exciting power of this new modality.”
Generally speaking, no matter which technology platform is used, protein degraders work by binding to the protein of interest. There is usually a linker molecule and a binder molecule to ubiquitin ligase. When the degrader binds to the protein, it tags it with the ubiquitin ligase that stimulates its destruction.
Still, the differences in technical approaches matter. “We’ve been interested in the protein degrader approach for a number of years and following the field as it matured,” Linda Higgins, senior vice president of Biology at Gilead told BioWorld. “What ultimately attracted us to select Nurix was their deep expertise in the biology of E3 ligases, understanding that from a number of different angles, including the degradation angle.”
Nurix has built a DNA-encoded library of small molecules designed for identifying good molecules for degraders. The company has also found 16 more ligases that were not previously involved in drug development.
Higgins told BioWorld that oncology drug development was one area of interest, but that the company sees potential “across targets that are difficult to address using more conventional small molecule means, those that one would like to degrade because simple inhibition will not be sufficient or as good as degradation, or those that don’t have a conventional small molecule binding pocket and aren’t amenable to the more conventional approaches.”