IFM Therapeutics is unveiling its second subsidiary: IFM Due, which will target the cyclic GMP-AMP Synthase, Stimulator of Interferon Genes (cGAS/STING) pathway to treat inflammatory and autoimmune disease. The launch follows that of the company’s first subsidiary, which is working on NLRP3 antagonists for the treatment of inflammatory diseases.
IFM CEO Gary Glick declined to disclose how much funding IFM Due—pronounced do-way, as in the Italian word for “two”—is launching with, but said the parent company would be more forthcoming as the year goes on. The NLRP3-focused IFM Tre debuted last July with a $31 million series A, drawn from the likes of Atlas Venture, Abingworth and Bristol-Myers Squibb, as well as IFM itself.
The cGAS/STING pathway is part of the innate immune system that senses when DNA is in the cytosol—the fluid found inside cells—instead of being in the cell nucleus. This “danger signal” triggers the production of interferon and other pro-inflammatory cytokines. IFM Due will develop cGAS inhibitors and STING antagonists to combat the excessive production of pro-inflammatory cytokines in an approach that could be applied to a wide range of diseases.
Glick sees them in two buckets: diseases resulting in from mutations in STING and other proteins in the pathway that lead to the overproduction of interferon and those with aberrant cGAS/STING activation stemming from an overproduction of nucleic acids in the cytosol, where they shouldn’t be.
It’s still early to say which indications IFM Due is gunning for, but they could include rare diseases such as Aicardi-Goutières syndrome, STING-associated vasculopathy with onset in infancy and a subset of systemic lupus erythematosus as well as nonalcoholic steatohepatitis, age-related macular degeneration and Parkinson’s disease.
Specifically, IFM Due is working on two preclinical programs: an orally available, small-molecule STING antagonist that’s slated to enter the clinic in 2020 and a small-molecule cGAS inhibitor that’s a little further behind.
While cGAS and STING aren’t new to biotech, they are challenging to target.
“Folks have tried and tried and not been able to get anything in terms of small molecules that are progressible,” Glick said. IFM is hoping that with its “secret sauce” and the guidance of Andrea Ablasser, who joined IFM as a scientific advisor and IFM Due as its founding scientist, it will be able to go where others haven’t.
And IFM isn’t the only one who thinks it’s got an edge on STING. In January, Aduro Biotech laid off 37% of its employees and “deprioritized” several assets so it could throw its weight behind its lead programs, including a STING program in development for multiple tumors.