M107 is an oral, small molecule that is a best-in-class PPARγ activator. M107 is approved in South Korea for the treatment of Type 2 diabetes and has an existing safety database and six-year post-marketing surveillance data of over 3,600 subjects. M107 is a new chemical entity (NCE) in the United States, Europe, Japan and China.
Macrophages are tissue-resident or infiltrated immune cells critical for innate immunity, normal tissue development, homeostasis and repair of damaged tissue. Macrophages are primarily categorized into two groups: Pro-inflammatory M1 and anti-inflammatory M2. In gastroparesis, an increase in M1 pro-inflammatory macrophages in stomach tissue generates oxidative stress thereby reducing and/or damaging Interstitial Cells of Cajal (ICC), a core part of the gastric pacemaker system. These changes result in stomach paralysis and decreased gastric emptying. M107 works to stimulate M2 anti-inflammatory macrophages and switch the M1 pro-inflammatory macrophage phenotype to the M2 anti-inflammatory macrophage phenotype, thereby increasing the ICC population and supporting the restoration of normal gastric pacemaker function. M107 also decreases fibrosis of the gastric pylorus at the exit of the stomach.
M107 represents a potential disease-modifying therapy as it targets the underlying mechanism of disease. Other drugs on the market today treat just the symptoms of gastroparesis and not the core biology.
In vivo testing of M107 has demonstrated excellent on-target effects promoting increased expression of M2 macrophages, decreased number of M1 macrophages, and reduction of inflammatory markers. Human testing has shown a much improved off-target safety profile for M107 compared to earlier PPARγ molecules.
M107 is protected by pending patent families covering methods-of-use and biology for multiple gastrointestinal, kidney and other diseases until 2043. Utilizing M107’s existing safety database and other developmental work, Aclipse conducted a successful pre-IND meeting with the FDA and intends to initiate a Phase 2 clinical trial of M107 in gastroparesis.
M107 may be eligible for additional FDA regulatory exclusivities and/or programs, including Fast Track, Breakthrough Therapy, Priority Review and NCE exclusivities at the appropriate times of drug development.
Due to its potent anti-inflammatory activity, M107 has significant potential upside in other diseases areas with significant unmet patient needs. We are currently evaluating M107 for potential use in several rare diseases.
