Freshly funded IFM Therapeutics defines emerging target for fighting inflammatory disease

Pills and vitamins
IFM Therapeutics is developing pills that block the "inflammasome" NLRP3. (Steven Depolo/CC BY 2.0)

Just two weeks after hauling in a $31 million series A funding round to form a new subsidiary, Boston-based IFM Therapeutics is laying out a case for the unit’s primary drug target: a signaling receptor called NLRP3. The authors said in a new publication that advances in the understanding of NLRP3’s activity are making it possible to develop small molecules to treat a range of inflammatory diseases.

IFM was launched into the spotlight last August, when Bristol-Myers Squibb acquired the company to gain access to its oncology pipeline, in a deal that could be worth up to $2.3 billion. NLRP3 agonists were included in that transaction, but IFM’s existing personnel were able to form a separate company to focus on NLRP3 in inflammatory diseases and fibrosis.

BMS participated in the most-recent funding, which resulted in IFM setting up a separate unit called IFM Tre to focus on developing NLRP3 antagonists. It expects to start phase 1 trials of its lead candidate next year.

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NLRP3 allows immune cells to detect foreign invaders that signal tissue damage or infection, the company’s researchers explained in a paper published in the journal Nature Reviews Drug Discovery. That touches off the assembly of proteins into an “inflammasome,” which then triggers an immune response.

The activation of the NLRP3 inflammasome causes pro-inflammatory molecules to be released in the body, such as IL-1 and IL-18, the authors wrote. That process can cause a range of auto-immune disorders, including Crohn’s and Alzheimer’s. IFM’s scientists are working on small molecules that will inhibit inflammation without affecting other immune processes in the body.

RELATED: IFM Therapeutics' inflammation-focused subsidiary debuts with $31M

“The growing body of literature about NLRP3’s role in the pathogenesis of diseases validates it as a promising target for new therapies,” said co-author and IFM co-founder Eicke Latz, M.D., Ph.D., director of the Institute of Innate Immunity at the University of Bonn, in a release.

Other IL-1 blockers are on the market, including Amgen’s Kineret to treat rheumatoid arthritis, but “the direct targeting of NLRP3 has both potential efficacy and safety advantages over these biologics,” Latz and his colleagues wrote in their paper.

IFM Tre’s lead pipeline asset binds to NLRP3 outside the central nervous system, which blocks its activity by preventing it from changing shape in a way that would normally allow for the release of IL-1 and IL-18. The company has not yet announced which inflammatory diseases will be included in the upcoming phase 1 trial. It is also working on two separate drugs to treat inflammatory bowel disease and Alzheimer’s.

IFM is not alone in its interest in NLRP3 antagonists for treating inflammatory diseases. In June, U.K.-based Nodthera raised $40 million in a series A to advance its NLRP3 inflammasome inhibitor to human trials.

Latz and his colleagues make a strong case in their review that the proliferation of diseases characterized by an “overly active NLRP3” calls for a therapeutic approach to interfering with the pathway. The development of safe ways to inhibit NLRP3 has been hampered by a basic misunderstanding of the pathway’s “central activation mechanisms,” they wrote.

“Future studies identifying the mechanism of action of these compounds will help determine the activation mechanism of NLRP3, as well as assist in determining potential off-target effects of the compounds,” they added.