ImmuneSensor Therapeutics Receives Clearance  to Initiate First-in-Human Phase 1 Clinical Trial of cGAS inhibitor Drug Candidate

ImmuneSensor Therapeutics recently announced it has received Human Research Ethics Committee (HREC) approval and Clinical Trial Notification (CTN) clearance by the Australian Therapeutic Goods Administration (TGA) to initiate a Phase 1 randomized placebo-controlled, double-blinded clinical trial of its lead anti-inflammatory and autoimmunity drug candidate, IMSB301, in healthy volunteers. IMSB301 is a novel, orally available small molecule cGAS inhibitor that is being developed for the treatment of inflammatory and autoimmune diseases.

“Receiving HREC approval and CTN clearance for the first clinical trial of our novel cGAS inhibitor is a significant milestone for ImmuneSensor as we pursue our goal to bring innovative therapeutic interventions to those battling autoimmune and other inflammatory diseases,” said Tom Dubensky, PhD, ImmuneSensor’s President and Chief Executive Officer. “The initial dose finding portion of our Phase 1 trial of IMSB301 in healthy volunteers will provide important early safety and target engagement data that will inform rapid advancement to Phase 1b/2 clinical studies in patients with severe inflammatory diseases, including Aicardi Goutières syndrome (AGS), a rare inflammatory disease that is specifically driven by chronic activation of the cGAS pathway in these patients, and in defined patient populations with systemic lupus erythematosus (SLE).”

The Phase 1 randomized, placebo-controlled, double-blind clinical trial is designed to evaluate the safety and tolerability, and pharmacokinetics (PK) of single and multiple escalating doses of IMSB301 and to demonstrate target engagement. The study will enroll healthy volunteers in cohorts of eight subjects (two will be given placebo and six dosed with IMSB301) given up to five single ascending dose (SAD) levels over two days, and subsequently up to three multiple ascending dose (MAD) levels. The primary endpoint is safety and tolerability, PK will be assessed in both SAD and MAD arms and target engagement will be evaluated using an ex vivo whole blood DNA stimulation assay in the MAD arm.

The cGAS-STING pathway works to detect both host-derived and foreign cytoplasmic DNA produced as a result of infection or cell damage due to inflammation or malignancy. In autoimmune diseases, the innate immune response is chronically activated, directly promoting inflammation and the development of autoimmunity, both in the periphery and central nervous system (CNS). IMSB301 is a novel, orally available small molecule designed to specifically inhibit the cGAS enzyme and stop pathologic inflammation. In preclinical studies, IMSB301 has been demonstrated to be a potent and specific inhibitor of cGAS enzymatic activity that results in a profound suppression of cytokine production and rescue of the disease phenotype and premature death in a model of AGS. ImmuneSensor is developing IMSB301 initially in cGAS-driven Type I interferonopathies including AGS and SLE. IMSB301 has the potential to address other diverse therapeutic areas that are characterized by cGAS-driven inflammation including diabetic kidney diseases, age-related macular degeneration, and other autoimmune disorders.

AGS is a rare genetic severe inflammatory disease of immune cells affecting the brain (demyelination) and peripheral tissues (lungs, liver, heart, skin) caused by mutations in upstream cytosolic nuclease genes, including TREX-1, that triggers chronic production of type I interferon (IFN-I) and additional pro-inflammatory cytokines resulting from chronic activation of cGAS and the production of downstream signaling molecules. The disease has no cure and is currently treated with drugs designed to manage symptoms.

SLE is a complex autoimmune disorder that can be associated with the dysregulated production of IFN-I and other pro-inflammatory cytokines, which is thought to play a pivotal role in the pathogenesis of the disease. The disease characterized by heterogeneous clinical manifestations, involving the skin, blood vessels, kidneys and central nervous system that can result in serious organ damage and appears to develop when individuals with a genetic predisposition for the disease come into contact with an environmental “trigger.” The CDC estimates that approximately 204,000 people in the United States have SLE, the most common type of lupus, with nine times as many women as men likely to develop the disease. Current standard of care involves treatment with anti-inflammatory drugs and immunosuppressants.

ImmuneSensor is a privately held, clinical stage company founded on the groundbreaking discovery of cGAS and cGAMP along with their combined role in regulating immunity, by Dr. Zhijian Chen’s laboratory at the University of Texas Southwestern Medical Center, a breakthrough that has profoundly impacted both the scientific and pharmaceutical fields. ImmuneSensor is dedicated to developing best-in-class small molecule inhibitors and agonists of the cGAS-STING signaling pathway to potentially address therapeutic areas with significant unmet medical need in autoimmunity, inflammation and oncology. For more information, visit: www.immunesensor.com.