Pasithea Therapeutics Announces Preclinical Data that Shows PAS-004 Inhibits ETS2 Signaling, a Key Driver of Inflammation in IBD and Other Large Addressable Market Diseases

Core Insights - Pasithea Therapeutics Corp. has announced new preclinical data indicating that PAS-004, a next-generation macrocyclic MEK inhibitor, demonstrates superior inhibition of ETS2-driven inflammatory responses compared to the FDA-approved MEK inhibitor selumetinib in a human macrophage model of chronic inflammation [1][3] Group 1: Study Findings - The study conducted at the Francis Crick Institute shows that PAS-004 consistently outperforms selumetinib across all tested doses (0.01 μM, 0.1 μM, and 1 μM), indicating more robust and durable MEK inhibition under inflammatory conditions [2][3] - PAS-004 exhibits superior suppression of ETS2 signaling, with greater downregulation of ETS2-regulated genes than selumetinib at all doses tested [3][4] - PAS-004 significantly reduces ETS2-dependent macrophage functions such as cytokine production, phagocytosis, and reactive oxygen species (ROS) generation, which are central to chronic inflammation [4] Group 2: Mechanistic Insights - Gene Set Enrichment Analysis reveals that PAS-004's effects closely mirror ETS2 knockout profiles, showing a higher normalized enrichment score (-3.96 vs -3.56) and greater statistical significance (1.2 x 10⁻²⁵⁰ vs 3.7 x 10⁻⁷⁴) compared to selumetinib [4] - The ability of PAS-004 to block ETS2 signaling suggests it may target multiple cytokines, including TNFα, IL-23, and IL-1β, which are critical in chronic inflammatory diseases [4] Group 3: Future Potential - The company believes that PAS-004 has the potential to be a new oral treatment option for inflammatory diseases such as inflammatory bowel disease (IBD), based on low adverse events and tolerable safety data observed in Phase 1 clinical trials [4][5] - The preclinical results suggest that PAS-004's ability to block ETS2 signaling and target multiple cytokines opens the potential for testing in large market inflammatory indications [5]