IFM Therapeutics is hiving off its NLRP3 stable into a subsidiary dubbed IFM Tre. The new unit, which starts out with $31 million in series A funding, expects to bring its lead asset into phase 1 in 2019.
While IFM Tre will focus on NLRP3 antagonists for the treatment of inflammatory diseases, other subsidiaries within IFM Therapeutics will continue work on other programs targeting the innate immune system, according to a statement. These include an AIM2 antagonist for use in oncology, as well as inflammation-focused molecules, including an NLRP1 antagonist, a STING antagonist and a cGAS inhibitor.
NLRP3 inflammasomes are protein complexes that form part of the body's natural defense against pathogens. Specifically, they are responsible for activating the inflammatory response, which releases interleukins to address infection. When this process goes awry—as a result of diet, environmental stresses or genetics—it drives the onset and progression of various conditions, such as metabolic, fibrotic, autoimmune and neurodegenerative disease.
“Based on substantial preclinical and translational data suggesting the therapeutic effects of NLRP3 inhibition, we believe our small molecules may selectively reduce the immune responses that cause the body to attack itself and prevent overactive inflammation from occurring," said IFM Therapeutics CEO Gary Glick, Ph.D.
Targeting the NLRP3 pathway allows for the treatment of symptoms without interfering in other immune pathways, the company said. This avoids issues that come with systemic immunosuppression.
IFM Tre's lead candidate blocks NLRP3 activity by binding to it outside the central nervous system. This prevents a shape change that leads to the maturation of the interleukins IL-1 and IL-18. Phase 1 trials in healthy volunteers are slated to start next year. The subsidiary also has a gut-directed NLRP3 asset, which is in development for inflammatory bowel disease, but could also be part of a combo regimen with systemic immunosuppressive drugs, the company said. Its third asset is a CNS-penetrant molecule in the works for Alzheimer's and other neurodegenerative and neuroinflammatory conditions.
IFM Tre is backed by Atlas Venture, Abingworth and Bristol-Myers Squibb, the Big Pharma that inked a deal worth up to $2.3 billion to acquire IFM Therapeutics and its immuno-oncology pipeline last August.
And it's not the only company working on NLRP3—Cambridge, U.K.-based Nodthera raised $40 million in its own series A in June to bring an NLRP3 inflammasome inhibitor through to proof of concept in humans. Nodthera is helmed in the interim by CSO Alan Watt, a biopharma veteran who’s worked at Merck, GlaxoSmithKline and Bicycle Therapeutics, first worked on NLRP3 during his time at GlaxoSmithKline.