Novartis and IFM Therapeutics Forge $840M Collaboration to Advance Novel Immunotherapies Targeting the cGAS/STING Pathway

Today, IFM Therapeutics, a biopharmaceutical company dedicated to developing innovative therapies targeting the innate immune system, announced that its subsidiary, IFM Due, has entered into a research and development agreement with Novartis. The two parties will collaborate on the development of a series of innovative immunotherapies inhibiting the cGAS/STING signaling pathway for the treatment of various severe inflammatory and autoimmune diseases. Previously, IFM Therapeutics had entered into an R&D collaboration with Novartis to develop anti-inflammatory therapies based on the NLRP3 target.

Cyclic GMP-AMP synthase (cGAS) catalyzes the synthesis of cyclic GMP-AMP (cGAMP), which activates the stimulator of interferon genes (STING), thereby triggering a cascade of downstream molecular activation and ultimately inducing the production of type I interferons (IFNs). The cGAS/STING signaling pathway was initially identified as a crucial component of the innate immune system. This pathway is involved in recognizing microbial DNA and self-DNA that have entered the cytoplasm, and it plays a significant role in the pathogenesis of infectious diseases and autoimmune disorders.

Mutations that activate this signaling pathway can cause a variety of severe autoinflammatory and autoimmune diseases, including a series of rare disorders such as Aicardi-Goutières syndrome (AGS), STING-associated vasculopathy with onset in infancy (SAVI), and systemic lupus erythematosus (SLE). Aberrant activation of the cGAS/STING signaling pathway also contributes to several common diseases; for instance, in the context of mitochondrial dysfunction, it can lead to non-alcoholic steatohepatitis (NASH), chronic obstructive pulmonary disease (COPD), age-related macular degeneration (AMD), and Parkinson’s disease.

▲ Both hyperactivity and hypoactivity of the innate immune system can lead to serious diseases (Image source: IFM Therapeutics official website)

IFM Therapeutics has developed small-molecule antagonists and inhibitors targeting aberrant inflammatory responses of the innate immune system, addressing a range of indications including rare diseases, autoimmune disorders, fibrotic conditions, and neurodegenerative diseases. Currently, the company has two preclinical programs in development: one is an oral small-molecule STING antagonist that blocks STING-mediated overproduction of interferons and other pro-inflammatory cytokines, with clinical trials anticipated to commence in 2021; the other is a small-molecule inhibitor of cGAS, designed to block signaling at a more upstream node in the pathway.

▲IFM Due R&D Pipeline (Image source: IFM Therapeutics official website)

Under the terms of the agreement, Novartis will provide substantial funding for IFM Due’s cGAS/STING research and development program in exchange for an option to acquire IFM Due. Upon exercise of this option, the shareholders of IFM Due will be entitled to receive total payments of up to $840 million.

“The cGAS/STING pathway, which leads to the overproduction of interferon and other pro-inflammatory cytokines, is a potential disease driver; precisely targeting this signaling pathway represents a highly attractive therapeutic approach,” said Dr. H. Martin Seidel, Executive Vice President of Development at IFM Therapeutics. “We are delighted to collaborate with Novartis once again. Like us, Novartis believes that therapies blocking the cGAS/STING pathway hold significant therapeutic potential.”

References:

[1] IFM Therapeutics Announces Collaboration and Exclusive Option Agreement for cGAS/STING-Focused Subsidiary, IFM Due, Retrieved September 05, 2019, from https://www.prnewswire.com/news-releases/ifm-therapeutics-announces-collaboration-and-exclusive-option-agreement-for-cgassting-focused-subsidiary-ifm-due-300912026.html

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