ImmuneSensor Therapeutics Gets Australian Approval for First Human Trial of Drug IMSB301

ImmuneSensor Therapeutics, a clinical-stage biotherapeutics company known for its work on innovative inhibitors and agonists targeting the cGAS-STING pathway, has announced a major milestone. The company received approval from the Human Research Ethics Committee (HREC) and Clinical Trial Notification (CTN) clearance from the Australian Therapeutic Goods Administration (TGA) to start its Phase 1 clinical trial for its lead drug candidate, IMSB301, in healthy volunteers. This approval marks a significant step forward for the company in its mission to develop treatments for inflammatory and autoimmune diseases.

IMSB301 is a novel, orally administered small molecule designed to inhibit the cGAS enzyme, which is pivotal in inflammatory and autoimmune diseases. This drug aims to block the signaling through a central pathway that drives various inflammatory conditions. ImmuneSensor plans to initiate the Phase 1 trial in the third quarter of 2024, with the goal of advancing swiftly into Phase 1b/2 clinical studies focusing on Type I interferonopathies.

Tom Dubensky, Ph.D., president and CEO of ImmuneSensor, emphasized the importance of this milestone. He pointed out that the initial phase of the trial will focus on finding the appropriate dosage and will provide crucial early safety and target engagement data. This will facilitate rapid progression to more advanced clinical studies involving patients suffering from severe inflammatory diseases like Aicardi Goutières syndrome (AGS) and systemic lupus erythematosus (SLE). AGS is a rare inflammatory disease specifically driven by chronic activation of the cGAS pathway, while SLE is a complex autoimmune disorder that affects multiple organs.

The IMSB301 Phase 1 clinical trial is designed as a randomized, placebo-controlled, double-blind study. It aims to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple escalating doses of IMSB301. The study will enroll healthy volunteers in cohorts of eight subjects, with six receiving IMSB301 and two receiving a placebo. The trial will comprise up to five single ascending dose levels over two days, followed by up to three multiple ascending dose levels. The primary focus will be on safety and tolerability, while PK and target engagement will also be assessed using an ex vivo whole blood DNA stimulation assay in the multiple dose arm of the study.

The cGAS-STING pathway detects both host-derived and foreign cytoplasmic DNA resulting from infection or cell damage. In autoimmune diseases, this pathway is chronically activated, leading to continuous inflammation and autoimmunity. IMSB301 aims to inhibit the cGAS enzyme, thereby stopping pathological inflammation. Preclinical studies have shown that IMSB301 is a potent inhibitor of cGAS enzymatic activity, significantly suppressing cytokine production and improving disease symptoms in models of AGS. The drug has the potential to treat various conditions characterized by cGAS-driven inflammation, such as diabetic kidney diseases and age-related macular degeneration.

Type I interferonopathies, including AGS and SLE, are severe inflammatory and autoimmune diseases. AGS is a rare genetic disorder affecting the brain and peripheral tissues, caused by mutations that trigger chronic production of type I interferon and other pro-inflammatory cytokines. SLE, on the other hand, is a complex autoimmune disorder with a wide range of clinical manifestations, including skin, blood vessel, kidney, and central nervous system involvement. Both diseases currently lack curative treatments and are managed with drugs that control symptoms.

ImmuneSensor Therapeutics is a privately held company founded on the discovery of the cGAS and cGAMP enzymes, which play a crucial role in regulating immunity. The company is committed to developing best-in-class small molecule inhibitors and agonists of the cGAS-STING pathway to address unmet medical needs in autoimmunity, inflammation, and oncology.