BellBrook Labs has been awarded a $300,000 SBIR grant by The National Institute of Allergy and Infectious Diseases (NIAID) to develop novel inhibitors for cyclic GAMP Synthase (cGAS), a promising therapeutic target for autoimmune diseases, including lupus.
The enzyme cGAS acts as a trigger for activation of an innate immune response to cytoplasmic DNA that results from microbial infection or genotoxic events. Once alerted, cGAS triggers a robust type I interferon response by producing the second messenger, cGAMP, which acts as an agonist for the stimulator of interferon genes (STING) receptor.
Aberrant activation of the cGAS-STING pathway by self-DNA has emerged as an underlying cause of terrible and often fatal monogenic autoimmune disorders such as Aicardi-Goutieres Syndrome (AGS). Systemic lupus erythematosus (SLE) is another debilitating disorder where the pathway has shown to be a cause in a significant population of those affected by the disease. Using a small molecule inhibitor to block the cGAS enzyme from producing cGAMP could provide a more effective therapy for AGS and SLE with the potential to impact millions of people affected by debilitating autoimmune disorders.
Presently, there are no drugs approved specifically for interferon-driven autoimmune disease. Current IFN-targeted therapies in clinical development are mostly biologics, such as antibodies against IFNα or the IFN receptor. Targeting cGAS may provide a more efficacious upstream solution, and a small molecule therapeutic would have decided advantages in terms of cost, dosing, and CNS exposure.
BellBrook has assembled a robust, highly efficient cGAS discovery platform and is well positioned to develop a first-in-class lead molecule. A decided advantage in terms of cGAS lead discovery is the Transcreener cGAS Assay, based on BellBrook’s flagship platform that has been proven by pharmaceutical companies globally for over 10 years. The biochemical assay has enhanced the company’s cGASlead discovery program by enabling robust HTS and rapid SAR.