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CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Nimbus Therapeutics, a biotechnology company designing breakthrough medicines through structure-based drug discovery and development, today published research in the Proceedings of the National Academy of Sciences describing the structural basis for isoform-specific inhibition of human CTPS1 (CTP synthase 1). Selective inhibition of CTPS1 is a promising approach for the treatment of autoimmune and other T cell-driven diseases, but little is known about the mechanisms underlying selective versus non-selective inhibition. Nimbus scientists, in partnership with researchers from the University of Washington and Schrödinger, used cryo-electron microscopy (cryo-EM) to characterize the activity of CTPS inhibitors in binding to, inhibiting and distinguishing between CTPS1 and its isoform CTPS2. The cryo-EM research was funded by Nimbus and led by professor Justin Kollman at the University of Washington. “We’re proud to have conducted this impactful research in partnership with our valued colleagues at University of Washington and Schrödinger, further building on Nimbus’ long history of fruitful academic collaborations,” said Peter Tummino, Ph.D., Chief Scientific Officer at Nimbus. “The insights we have published will be instrumental in our efforts to develop selective inhibitors of CTPS1 that can potentially offer a powerful new means of treating autoimmune diseases and T cell-driven cancers.” “A defining feature of Nimbus’ structure-based drug discovery approach is our use of leading-edge computational technology, including cryo-EM, to characterize drug targets in unprecedented detail,” said Scott Edmondson, Ph.D., Senior Vice President and Head of Chemistry at Nimbus. “The discoveries made in this research, together with Nimbus’ expertise in computational chemistry, molecular sciences and disease biology, will inform our ongoing development of highly selective small-molecule CTPS1 inhibitors.” The paper, entitled “Structural basis for isoform-specific inhibition of human CTPS1,” published online in the Proceedings of the National Academy of Sciences this week: . 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. Nimbus is headquartered in Cambridge, Mass.

The search for better T and B cell therapies have absorbed billions in R&D funds from some of the biggest drugmakers in the world. A French biotech thinks it could have a hyper-focused approach to T and B cell malignancies, and it’s taking home a decent-sized check to race to the clinic. Step Pharma has bagged $41.5 million in funding to take its lead CTPS1 inhibitor into clinical trials for T cell malignancies by the first quarter of 2022, the French biotech said Wednesday. The company’s science was based on the work of French immunologist Alain Fischer, who identified a genetic connection between the CTP synthase 1 enzyme and the inability of normal B and T cells to proliferate in patients. The company was initially seeded in 2015, and current CEO Andrew Parker stepped in about 18 months ago to help drive the company into Phase I studies. Step believes its focus on the CTPS1 enzyme can offer a hyper-targeted approach to spur T cells and B cells to target aggressive tumors. “The genetics told us that if you block CTP synthase 1, you’ve got this very specific effect on T and B cells,” Parker said. “That’s what really gives this a very targeted approach to inhibit proliferation of B cells and T cells and spare other cell types.” The initial Phase I, scheduled to enroll in the EU given the company’s established presence in France, will operate as a five-arm “basket study,” Parker said, with three arms focusing on T cell hematologic malignancies and two arms focusing on B cell conditions. If any arm shows clinical promise, the biotech plans to expand enrollment up to 35 patients in Phase II proof-of concept studies. In T cell lymphomas, Step believes a 35-patients study in the Phase II setting could be enough for a breakthrough designation and fast track, Parker said. Meanwhile, the B cell arms would likely require Phase III studies as they would apply to third-line-or-later patients. With the EU equivalent of an IND set for early 2022 — in the January or February range, by Parker’s count — Step is planning to expand its small team of five to around 10 as it enters the clinic. The round was co-led by new investors Hadean Ventures and Sunstone Life Science Ventures, which joined existing investors Kurma Partners, Pontifax and Bpifrance, which reinvested through its Innovative Biotherapies and Rare Diseases fund and InnoBio 2 fund. As part of the financing, Jacob L. Moresco from Sunstone Life Science Ventures and Walter Stockinger from Hadean Ventures will join the board.