ImmuneSensor Therapeutics Granted New US Patent for its Oral cGAS Inhibitors

ImmuneSensor Therapeutics recently announced the United States Patent and Trademark Office (USPTO) has issued US patent No. 12,091,387 containing claims covering compositions of matter and methods of use of ImmuneSensor’s proprietary potentially best-in-class cGAS inhibitors for a variety of inflammatory conditions, including allergic, autoimmune, cardiovascular, ocular inflammation, and neurodegenerative diseases.

“The granting of this patent is a critical step in protecting our proprietary approach to effectively drug cGAS, and provides ImmuneSensor a competitive edge in the ongoing development of our novel orally available small molecule cGAS inhibitors for the potential treatment of a broad range of inflammatory, autoimmune, metabolic and neurodegenerative disorders,” said Tom Dubensky, PhD, ImmuneSensor’s President and Chief Executive Officer. “As a central mediator of inflammation, the cGAS-STING pathway has been recognized as a potentially high-value therapeutic target. However, it has historically been very difficult to drug. This patent builds on our foundational intellectual property generated in the lab of Dr. James Chen, who first defined the biology of the cGAS enzyme and its signaling molecule, cGAMP, which serves as the foundation for ImmuneSensor’s development of best-in-class small molecule inhibitors of cGAS to address unmet medical need in inflammatory diseases.”

ImmuneSensor is initiating a Phase 1 randomized, placebo-controlled, double-blind clinical trial of its lead cGAS inhibitor drug candidate, IMSB301, in healthy volunteers in Australia. The study is designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple escalating doses of IMSB301 and to demonstrate target engagement. ImmuneSensor plans to initiate Phase 1b/2 clinical studies in selected patients with severe inflammatory diseases known as Type 1 interferonopathies, including Aicardi Goutières syndrome (AGS), a rare inflammatory disease that is specifically driven by chronic activation of the cGAS pathway, and in defined patient populations with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE).

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 the 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.

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.

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.

CLE is an autoimmune disease that causes the body’s immune system to attack healthy skin cells, resulting in a red, scaly rash. There are several types of CLE that are often triggered by sunlight, it can also arise as a complication of SLE. While it can affect people of any age or gender, it is most common among women 20 to 50 years old. There is no cure for CLE, and it symptoms are currently managed with drugs and lifestyle changes.

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.