May 15, 2020

Nimbus Therapeutics Announces Identification of a Potent, Selective HPK1 Inhibitor with Robust In Vivo Activity

Data to be presented at 2020 AACR Annual Meeting show HPK1 inhibition produced robust anti-tumor response in mouse model

CAMBRIDGE, Mass. – May 15, 2020 – Nimbus Therapeutics, a biotechnology company designing breakthrough medicines through structure-based drug discovery and development, today announced the identification of an HPK1 inhibitor with highly potent and selective anti-tumor activity in preclinical models. The data will be presented at the AACR Virtual Annual Meeting II, June 22-24, 2020.

HPK1 (hematopoietic progenitor kinase 1) is a highly valued target in immuno-oncology due to its role as a regulator of both T cell and dendritic cell activity. However, a key challenge for development of small molecules acting on HPK1 has been to achieve selectivity against other T cell kinases and MAP4K family members. Nimbus utilized its unique structure-based drug discovery engine to identify multiple potent and selective small molecule inhibitors of HPK1. One of these molecules, advanced to in vivo testing, has high selectivity against T cell-specific kinases and kinases in the MAP4K family and exhibits promising activation of human T cells and B cells. In a mouse syngeneic tumor model, oral administration of the HPK1 inhibitor completely eliminated HPK1’s phosphorylation of the T cell receptor, enhanced inflammatory cytokine production, and demonstrated robust tumor growth inhibition.

“We’re excited to pull back the curtain on Nimbus’ HPK1 program and share some of the progress we’ve made against a target that has evaded so many others’ efforts,” said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. “Nimbus’ unparalleled expertise in structure-based drug discovery allowed us to chart an entirely new approach to inhibiting HPK1. In addition, we have recently leveraged this approach to generate small molecules against a range of promising new targets, and we look forward to sharing details on these programs in the coming weeks.”

“These data support the potential of our HPK1 inhibitor to alter the tumor microenvironment to halt cancer’s immune evasion, which we think could be a powerful tool in today’s immuno-oncology arsenal,” said Peter Tummino, Ph.D., Chief Scientific Officer of Nimbus. “We are advancing this program into IND-enabling studies, with the goal of entering the clinic next year, and ultimately providing a new therapeutic approach to address the large unmet need among patients with cancer.” 

About Nimbus Therapeutics 

Nimbus Therapeutics designs breakthrough medicines. Utilizing its powerful structure-based drug discovery engine, Nimbus designs potent and selective small molecule compounds targeting proteins that are known to be fundamental drivers of pathology in highly prevalent human diseases and which have proven difficult for other drug makers to tackle. The company’s LLC/subsidiary architecture enables diverse and synergistic partnerships to deliver breakthrough medicines. Nimbus is headquartered in Cambridge, Mass.

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