ImmuneSensor Therapeutics Starts Phase 1 Trial of Lead cGAS Inhibitor IMSB301

ImmuneSensor Therapeutics, a clinical-stage biotherapeutics company, has announced the dosing of the first cohort of healthy volunteers in a Phase 1 clinical trial of its lead drug candidate, IMSB301. This trial marks a significant step in the development of IMSB301, a novel oral cGAS inhibitor aimed at treating a variety of inflammatory and autoimmune diseases.

The company specializes in developing inhibitors and agonists that target the cGAS-STING pathway, a key mediator of inflammation. This pathway's inhibition could potentially address a broad range of unmet medical needs across various inflammatory conditions. The technology and approach behind IMSB301 are based on the research of Dr. Zhijian "James" Chen, whose work earned him the 2024 Albert Lasker Basic Medical Research Award.

Tom Dubensky, Ph.D., President and CEO of ImmuneSensor, stated that data on safety, pharmacokinetics, and target engagement from the ongoing Phase 1 trial would be available by the end of 2024. This data could facilitate the swift transition into Phase 1b/2 clinical studies targeting patients with severe inflammatory conditions, particularly Type 1 interferonopathies. The first focus will be on Aicardi-Goutières syndrome (AGS), a rare inflammatory disease triggered by chronic activation of the cGAS pathway, followed by evaluations in cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE).

The Phase 1 trial, conducted in Australia, is a randomized, double-blind, placebo-controlled study enrolling healthy volunteers to assess the safety and tolerability of IMSB301. The trial will involve multiple cohorts, each consisting of eight subjects. Six of these subjects will receive IMSB301, while two will receive a placebo. The trial will include up to five single ascending dose (SAD) levels and up to three multiple ascending dose (MAD) levels. Pharmacokinetics will be analyzed in both the SAD and MAD arms, and cGAS target engagement will be evaluated in the MAD arm using an ex vivo whole blood DNA stimulation assay. The first dose cohort of the SAD arm has already been completed, with exposure levels and pharmacokinetics consistent with predictions based on nonclinical studies.

IMSB301 works by inhibiting the cGAS enzyme, thereby preventing the production of the cGAMP signaling molecule, which is responsible for pathological inflammation. In preclinical studies, IMSB301 has shown to be a potent and specific inhibitor of cGAS enzymatic activity, significantly reducing cytokine production and rescuing the disease phenotype in a model of AGS. Initially, ImmuneSensor will develop IMSB301 for cGAS-driven Type I interferonopathies, including AGS, CLE, and specific patient populations with SLE. The drug also has the potential to address other therapeutic areas characterized by cGAS-driven inflammation, such as diabetic kidney diseases, age-related macular degeneration, and other autoimmune disorders.

Type I interferonopathies, including AGS, SLE, and CLE, are severe inflammatory diseases driven by genetic mutations and chronic activation of the cGAS pathway. AGS is a rare genetic condition affecting both the brain and peripheral tissues, leading to chronic inflammation. SLE is a complex autoimmune disorder with various clinical manifestations that severely affect multiple organs. CLE, a form of lupus, primarily affects the skin, causing a red, scaly rash and is often triggered by sunlight.

ImmuneSensor Therapeutics is a privately held company founded on the discoveries of Dr. Zhijian Chen at the University of Texas Southwestern Medical Center. The company is dedicated to developing small molecule inhibitors and agonists targeting the cGAS-STING signaling pathway to address significant unmet medical needs in autoimmunity, inflammation, and oncology.