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Apr 12, 2021

New Review Examines the cGAS–STING Pathway as a Therapeutic Target in Inflammatory Diseases

Article in Nature Reviews Immunology was co-authored by IFM-affiliated researchers, including IFM Due co-founder Andrea Ablasser and IFM Therapeutics scientists Jason Katz and Shankar Venkatraman

BOSTON, April 12, 2021 — IFM Therapeutics, LLC (IFM), a privately-held biopharmaceutical company focused on developing therapies that modulate novel targets in the innate immune system to treat inflammatory disorders and cancer, today announced the publication of a new review article in Nature Reviews Immunology examining the biology, disease implications and therapeutic approaches toward targeting the cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway for the treatment of autoinflammatory, autoimmune and degenerative diseases. The collaboration was led by IFM Due co-founder Andrea Ablasser, M.D., of the Federal Institute of Technology Lausanne (EPFL), Switzerland, and included participation from IFM Therapeutics Senior Directors of Medicinal Chemistry, Jason Katz, and Shankar Venkatraman.

There are well-publicized drug-discovery efforts underway in identifying and translating agonists of the cGAS–STING pathway as anticancer immunostimulatory agents (such as IFM’s STING agonist program acquired by Bristol-Myers Squibb in 2017); however, this review covers 24 common and rare inflammatory diseases in which an inappropriately activated cGAS-STING pathway is implicated. A range of targeting strategies is discussed, including using cGAS inhibitors and STING antagonists, which IFM is pursuing through its IFM Due subsidiary under a collaboration and option deal with Novartis.

About the cGAS-STING Pathway

The cGAS-STING (cyclic GMP-AMP Synthase, Stimulator of Interferon Genes) pathway functions to sense cytosolic DNA, which is a signal of cellular danger, and then triggers a potent inflammatory response. Mutations that activate this pathway can cause a variety of serious autoinflammatory and autoimmune diseases in humans, including rare diseases such as Aicardi-Goutières syndrome (AGS), STING-associated vasculopathy with onset in infancy (SAVI), COPA syndrome and a subset of systemic lupus erythematosus (SLE). Aberrant cGAS-STING activation, such as in the setting of mitochondrial dysfunction, also underlies more common diseases such as nonalcoholic steatohepatitis (NASH), chronic obstructive pulmonary disease (COPD), amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD) and Parkinson's disease.

About IFM Due

IFM Due, a subsidiary of IFM Therapeutics, is a biopharmaceutical company developing a suite of small-molecule antagonists and inhibitors targeting aberrant inflammatory responses of the innate immune system triggered by the cGAS-STING pathway, which is believed to underlie a variety of serious diseases. The Company is developing small-molecule, orally available drug candidates to address a breadth of potential therapeutic indications, including rare, autoimmune, fibrotic, and neurodegenerative diseases. 

About IFM Therapeutics

IFM Therapeutics (IFM) is an independent, privately-held biopharmaceutical company based in Boston, Massachusetts. IFM’s team has discovered and developed small molecules that modulate novel targets in the innate immune system as next-generation therapies for cancer, autoimmunity, and inflammatory disorders. IFM places each program (or set of related programs) in its own dedicated, independently financed, R&D-focused subsidiary company, which is supported by the common infrastructure, management team and resources of the IFM enterprise. For more information on IFM and its model, please visit www.ifmthera.com.

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