M107 is an oral small molecule with best-in-class PPAR-γ activation. M107 is approved in one Asian country with 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. M107 is approved in South Korea with an existing safety database and six-year post-marketing surveillance data of over 3,600 subjects.
Macrophages are tissue-resident or infiltrated immune cells critical for innate immunity, normal tissue development, homeostasis, and repair of damaged tissue and primarily categorized into two main groups: Pro-inflammatory M1 and anti-inflammatory M2 macrophages. 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 increased gastric emptying time. M107 works to stimulate M2 anti-inflammatory macrophages and switch the M1 pro-inflammatory macrophage phenotype to the M2 anti-inflammatory macrophage phenotype, increasing the ICC population and supporting the restoration of normal gastric pacemaker function.
M107 represents the only potential disease-modifying therapy as it targets the M1:M2 axis, 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, increased the ratio of M2:M1 macrophages, reduced inflammatory markers, and a much improved off-target safety profile compared to earlier PPARγ molecules.
M107 is protected by pending patent families covering methods-of-use and biology for multiple gastrointestinal 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.
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.
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