On April 8, 2022 Nimbus Therapeutics, a clinical-stage company reported that designs and develops breakthrough medicines through its powerful computational drug discovery engine, is sharing preclinical data, on its Casitas B-lineage lymphoma b (Cbl-b) inhibitor, NTX-801, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting, being held April 8-13, 2022, in New Orleans, LA (Press release, Nimbus Therapeutics, APR 8, 2022, View Source [SID1234611683]).

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Cbl-b is an E3 ubiquitin ligase that is expressed in immune cells and, in the context of cancer, acts as a brake on the immune system, functioning as an intracellular checkpoint that negatively regulates T-cell activation, natural killer cell activity and immune response through degradation of specific proteins. Taken together, these factors make Cbl-b inhibition a potentially promising target for immuno-oncology.

Nimbus employed a structure-based drug design approach to identify small molecule inhibitors of Cbl-b. The inhibitor NTX-801 demonstrated strong immune cell activation and robust and statistically significant tumor growth inhibition in a mouse syngeneic tumor model. In combination with anti-PD-1, it resulted in robust anti-tumor activity, increased survival, and several complete responses, as defined by no measurable tumor in the murine tumor model.

"Preventing Cbl-b activity from dampening immune responses has long been seen as a promising potential way to enhance anti-tumor immunity. The preclinical data we are presenting today at AACR (Free AACR Whitepaper) support the promise of Cbl-b inhibition as a means of activating the immune response in vivo," said Peter J. Tummino, Chief Scientific Officer. "We look forward to further characterizing the Cbl-b inhibitors we have identified, and continuing to advance Cbl-b inhibition toward the clinic as a novel immuno-oncology approach."

The details of the poster presentation are as follows:

Title: Discovery of NTX-801, a Cbl-b inhibitor with antitumor activity in syngeneic models
Session Category: Immunology
Session Title: Immune Checkpoints
Session Date and Time: Sunday, April 10, 2022, 1:30 PM – 5:00 PM ET
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 38
Poster Number: 28