3:08 PM
 | 
Oct 05, 2017
 |  BC Innovations  |  Product R&D

Nimble move

Nimbus and Celgene go in for TYK and STING

Celgene Corp.’s deal with Nimbus Therapeutics LLC is another vote of confidence that Nimbus’ computational drug design technology can solve druggability problems that trip up standard medicinal chemistry. The partnership gives Celgene access to two promising but problematic autoimmune disease targets: TYK2 and STING.

In the partnership announced Oct. 3, Celgene agreed to pay Nimbus an upfront undisclosed fee to help fund the two programs through clinical proof of concept, at which point Celgene has an option to acquire each program for an additional fee. Nimbus is also eligible for milestones. Financial details are not disclosed.

Rupert Vessey, Celgene’s EVP and president of global research and early development, told BioCentury the Nimbus team will take the programs into the clinic to generate initial evidence of biological and clinical activity, and Celgene would be responsible for further development.

The partnership marks the fouther therapeutics deal for Nimbus, whose business model is to house its programs in separate subsidiaries for the express purpose of making them easier to sell off early in the development process.

Its earlier deals included a clinical stage program from its Nimbus Apollo Inc. subsidiary, sold to Gilead Sciences Inc. in 2016; a preclinical IRAK4 program from its Nimbus Iris Inc. subsidiary licensed to the Genentech Inc. unit of Roche in 2015, and a 2013 option deal with Shire plc to develop small molecules against an undisclosed target to treat lysosomal storage diseases.

The Gilead deal involved a portfolio of ACAC inhibitors for liver diseases, including GS-0976, an ACC inhibitor in Phase II testing for non-alcoholic steatohepatitis (NASH). Nimbus received $400 million up front and up to $800 million in development milestones, at least $200 million of which has been paid out. The Genentech deal gave the pharma an exclusive, worldwide license to develop and commercialize Nimbus’ IRAK4 inhibitors. Genentech is responsible for all preclinical and clinical development, manufacturing and commercialization.

In this week's deal with Celgene, both targets are immune signaling molecules that have strong genetic links to autoimmune disorders: TYK2 has been implicated in rheumatoid arthritis, lupus, Crohn’s disease, psoriasis and multiple sclerosis; STING is associated with lupus and other diseases driven by excess type I interferon signaling.

"If it’s something complex like both TYK2 and STING, where structural biology and computational chemistry can provide unique insights, then we really feel we have a leg up."

Donald Nicholson, Nimbus

Robert Plenge, VP of translational development and research and early development at Celgene, told BioCentury the genetic underpinning was a key factor in the selection of those targets.

"Genetics takes you to the target, it takes you to the mechanism, it takes you to the range of effect size that would be desirable, and it takes you to what potential adverse events could be," said Plenge.

Plenge said having biological data on a range of human TYK2 loss-of-function mutations provides a road map for the...

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