Ventus Therapeutics Provides Updates on cGAS Inhibitor Program at Keystone Symposium on Innate Immunity
- Category: Small Molecules
- Published on Monday, 17 April 2023 16:11
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WALTHAM, MA, USA & MONTREAL, Canada I April 17, 2023 IVentus Therapeutics, Inc., a biopharmaceutical company utilizing structural biology and a proprietary computational chemistry platform to identify and develop differentiated small molecule therapeutics across a broad range of diseases, announced the details of two presentations to be made at the Keystone Symposium on Innate Immunity: From Innate Sensing to Adaptive Responses, being held April 16-19 in Snowbird, Utah.
At the 8:00AM MDT Tuesday session, Ventus Chief Scientific Officer Michael Crackower, Ph.D., will present “Structure and Computation-Based Drug Discovery in Innate Immunity.” This presentation will mark the public debut of data showcasing the potency and pharmacokinetic profile of the company’s potential first-in-class cGAS inhibitor, VENT-03. Ventus’ portfolio of cGAS inhibitors have demonstrated modulation of key endpoints in models of lupus, dermal inflammation, and chronic kidney disease. Additionally, Dr. Crackower will present new data on the company’s portfolio of brain-penetrant NLRP3 inhibitors in a seizure model.
Additionally, Kelly Pike, Ph.D., Ventus head of translational sciences and scientific affairs, will present a poster during the 7:30PM MDT Monday poster session titled, “A Novel Selective Cyclic GMP-AMP Synthase (cGAS) Inhibitor Suppresses Systemic and Dermal Inflammation in a Model of Interferonopathy.” The poster outlines Ventus’ identification and optimization of a novel series of cGAS inhibitors, driven by unique structural insight. Dr. Pike will present evidence of robust suppression of systemic inflammation and protection against photosensitivity in a mouse model of auto-inflammation, supporting the therapeutic value of targeting cGAS for rheumatic diseases such as systemic lupus erythematosus (SLE).
“We are eager to share the latest VENT-03 data with our peers at the Keystone Symposium, as this audience represents individuals and organizations that have been instrumental in elucidating the biology of cGAS for more than a decade,” said Dr. Crackower. “We expect VENT-03 to be the first cGAS inhibitor ever to enter clinical trials and believe that the scientific community shares our excitement for this candidate’s potential to treat a range of immunological diseases, including lupus, systemic sclerosis, and dermatomyositis.”
cGAS is an intracellular pattern recognition receptor that is activated after binding to double-stranded DNA (dsDNA) in the cytoplasm. dsDNA in the cytoplasm is generally associated with cellular dysfunction, as seen in multiple diseases such as systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), and dermatomyositis (DM). cGAS activation leads to cGAMP formation, activation of STING and downstream expression of type I interferons such as IFN-α, -ß and -κ, leading to pronounced inflammation and tissue damage. This pathway also leads to the expression of several other proinflammatory cytokines such as CXCL10. Genetic mutations that lead to the aberrant activation of cGAS/STING in humans are known to cause severe infant onset Aicardi-Goutières Syndrome (AGS) and genetic forms of chilblain lupus, demonstrating the relevance of the pathway in human diseases. Given that the pathophysiology and presentation of these genetic diseases have significant similarities with idiopathic complex diseases such as SLE, CLE, and DM, these diseases represent highly compelling opportunities for treatment with a cGAS inhibitor.
NLRP3 is a member of a family of proteins known as inflammasome receptors and is integral in the formation of the NLRP3 inflammasome. Inflammasomes are multiprotein complexes that regulate the innate immune system and are involved in intracellular surveillance of danger signals that trigger an intense inflammatory response, including the release of IL-1β and IL-18 and the induction of pyroptosis, a lytic form of cell death. Therapeutic inhibition of NLRP3 can, therefore, prevent the formation of the NLRP3 inflammasome, which in turn inhibits the production of IL-1β and IL-18. Aberrant activation of the NLRP3 inflammasome has been associated with systemic conditions, including fibrotic, dermatological, and rheumatological diseases, and is a key driver of disease pathology in several neurological disorders, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis.
About Ventus Therapeutics
Ventus Therapeutics is a biopharmaceutical company deploying leading-edge structural biology and computational chemistry tools to create novel small molecule medicines for challenging targets, with an initial focus on immunology, inflammation, and neurology. The Company’s proprietary drug discovery platform, ReSOLVETM, gives it the ability to discover and develop medicines through unique insights into protein targets and to create dynamic blueprints that can guide the development of differentiated therapies at a fast pace. Ventus’ first target screen was conducted in 2020, which led to the nomination of three development candidates in 2022, including: VENT-03, a potential first-in-class cGAS inhibitor; VENT-02, a brain-penetrant NLRP3 inhibitor; and VENT-01, a peripherally restricted NLRP3 inhibitor. These programs exemplify Ventus’ unique discovery capabilities and focus on first- and best-in-class programs for multi-indication immunology targets with franchise potential. For more information, please visit www.ventustx.com and engage with Ventus on LinkedIn.
SOURCE: Ventus Therapeutics