EF-M2 (Immutalon) Multiple Ascending Dose Study in Moderate-to-Severe Rheumatoid Arthritis

This is a first-in-human, open-label, phase I/IIa, multiple ascending dose study of EF-M2 (Immutalon), a macrophage-modulating investigational product intended to shift macrophages toward an anti-inflammatory (M2-like) phenotype via a CLEC10A-mediated mechanism. The study will enroll adults with moderate-to-severe rheumatoid arthritis. Participants will receive EF-M2 as subcutaneous injections for 4 weeks in sequential dose cohorts (1, 3, 5, or 7 mcg administered twice weekly; optional expanded pharmacodynamic cohorts may receive 3 or 5 mcg three times weekly). The total number of injections will be 8-12 depending on the regimen. Dose escalation is sequential and overseen by an independent data safety monitoring board (DSMB), with sentinel dosing at the start of each new cohort. Participants may be followed off drug for up to 8-12 weeks after treatment, for a total participation time of up to 16 weeks (including screening). The primary objective is to evaluate safety, tolerability, and immunogenicity. Secondary objectives include assessing pharmacodynamic markers of M2 polarization (e.g., changes in ARG1/iNOS and IL-10/TNF-α ratios and M2-associated cell phenotypes) and exploring associations with clinical activity measures.