Celgene bags option on Nimbus' anticancer HPK1 inhibitor

Genentech filed multiple patents covering HPK1 inhibitors last year. (Celgene)

Celgene has expanded its deal with Nimbus Therapeutics to secure an option on an HPK1 inhibitor program. Nimbus will take the drug up to a clinical inflection point, at which time Celgene will choose whether to take up its option.

Computational chemistry specialist Nimbus partnered on Tyk2 and STING autoimmune programs with Celgene in 2017 but kept the rights to independently pursue the targets in the treatment of cancer. 

Now, Celgene has persuaded Nimbus to relax its grip on another, previously undisclosed oncology program. The financial terms of the deal will remain a secret until Celgene takes up its option to buy the program. Nimbus will control all R&D up to the option decision.

Celgene and Nimbus’ interest in HPK1 reflects evidence that the protein kinase is involved the control of both T-cell proliferation and dendritic cell activation. Based on the current science, Nimbus thinks small-molecule inhibitors of HPK1 can have positive effects on the two key immune cells and immunosuppressive tumor microenvironments. 

The challenge, as Nimbus sees it, is to hit the target without also inhibiting other T-cell kinases or MAP4K family members. Using its computer-enabled drug discovery capabilities, Nimbus thinks it can overcome that challenge to unlock the potential of HPK1.

Researchers began discussing HPK1 as a potential cancer immunotherapy target more than a decade ago, but interest in the protein kinase has ramped up in recent years as a fuller picture of its role in the regulation of T-cell function has emerged. 

Last year, a paper (PDF) published in Cell by Genentech researchers showed co-blockade of HPK1 and PD-L1 enhances antitumor responses, establishing the kinase as one of a clutch of targets with the potential to boost the efficacy of checkpoint inhibitors. Genentech filed multiple patents covering the use of azaindoles, isoquinolines and naphthyridines as HPK1 inhibitors last year.