ImmuneSensor Therapeutics Receives Orphan Drug and Rare Pediatric Disease Designations for  Aicardi Goutières Syndrome Treatment

ImmuneSensor Therapeutics recently announced the US FDA has granted both Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPDD) for the company’s lead anti-inflammatory and autoimmunity drug candidate, IMSB301 for the treatment of cGAS-driven Type I interferonopathy, Aicardi Goutières Syndrome (AGS). IMSB301, a novel, orally available small molecule cGAS inhibitor is also being developed for the treatment of inflammatory and autoimmune diseases, including systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE).

“Receiving both Orphan Drug and Rare Pediatric Disease designations for IMSB301 represents a significant milestone for ImmuneSensor and highlights the potential of this potent cGAS inhibitor to improve the lives of patients with AGS, a disease which is driven by chronic activation of the cGAS pathway,” said Tom Dubensky, PhD, ImmuneSensor’s President and Chief Executive Officer. “We currently have an ongoing Phase 1 trial of IMSB301 in healthy volunteers that will provide important early safety and target engagement data and inform rapid advancement to Phase 1b/2 clinical studies in patients with AGS and other severe inflammatory diseases, including lupus.”

The FDA’s Orphan Drug Designation program provides orphan status to therapies intended for the treatment, diagnosis, or prevention of rare diseases that affect fewer than 200,000 people in the United States. This designation provides certain benefits, including tax credits for qualified clinical testing, waiver or partial payment of FDA application fees and seven years of market exclusivity, if approved. The FDA defines a rare pediatric disease (RPD) as a serious or life-threatening disease primarily affecting individuals aged 18 years or younger that impacts fewer than 200,000 people in the US. The program is intended to facilitate development of new drugs and biologics for the prevention and treatment of RPDs. A substantial benefit of the RPDD is the potential for the sponsoring company to receive a priority review voucher (PRV) which is granted once the FDA approves the new drug application (NDA) for the product and indication having received the RPDD. A PRV can be redeemed by the sponsor to receive a priority review for any subsequent marketing application, or may be sold or transferred to another sponsor.

AGS is a rare genetic severe inflammatory disease in pediatric and adult populations, affecting the brain (demyelination) and peripheral tissues (lungs, liver, heart, skin) caused by germline mutations in upstream cytosolic nuclease genes, including TREX-1, that trigger chronic production of Type I interferon (IFN-I) and 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 resulting from chronic activation of cGAS, which is thought to play a pivotal role in the pathogenesis of the disease. The disease is 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 its symptoms are currently managed with anti-inflammatory drugs, immunosuppressants and lifestyle changes.

The cGAS-STING pathway works to detect (“sense”) 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 to prevent production of the cGAMP signaling molecule and halt 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, as well as CLE and selected patient populations with 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.

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 “James” Chen’s laboratory at the University of Texas Southwestern Medical Center. This breakthrough has profoundly impacted both the scientific and pharmaceutical fields and earned Dr. Chen the 2024 Albert Lasker Basic Medical Research Award. ImmuneSensor is dedicated to developing best-in-class small molecule inhibitors of the cGAS-STING signaling pathway to potentially address therapeutic areas with significant unmet medical need in autoimmunity and inflammation. For more information, visit www.immunesensor.com.