SynAct Pharma AB (publ) announced that dosing has been completed in the Phase 2a portion of the RESOLVE Phase 2a/b clinical study of once-daily oral resomelagon (AP1189) in patients with an inadequate response to first-line disease-modifying antirheumatic drugs (DMARD-IR). A total of 125 patients were randomized into the study with over 20% recruited in the US. With dosing completed SynAct anticipates releasing top-line study data in October of this year.

Development of resomelagon in DMARD-IR patients is being done under an IND (Investigational New Drug) application with clinical sites in the both the US and in European countries. RESOLVE is designed in two parts with a 4 week Phase 2a dose selection and initial safety and efficacy assessment portion that will enable dose selection for the 12 week Phase 2b safety and efficacy assessment. Planning and preparation for the Phase 2b study, i.e. part B of the FDA approved RESOLVE protocol, has begun.

RESOLVE (AP1189), is a once-daily oral melanocortin agonist that selectively activates melanocortin receptors 1 and 3 that are directly involved in inflammation and its resolution. These receptors are located on immune cells including macrophages and neutrophils. Activation of these receptors can result in both anti-inflammatory effects like lowering the level of pro- inflammatory molecules and in pro-resolution effects like switching macrophages to perform inflammation 'clean-up', known as efferocytosis (J Immun 2015, 194:3381-3388).

This dual effect has shown to be effective in disease models of inflammatory and autoimmune diseases and the clinical potential of the approach is currently tested in clinical programs in patients with rheumatoid arthritis (RA). The RESOLVE Phase 2a portion of theRESOLVE study was designed to enable effective dose selection for the Phase 2b study and to obtain proof of concept data on the safety and efficacy or resomelagon in this important patient population. The Phase 2a study was not powered to demonstrate a statistically significant difference between active and placebo groups.

A total of 125 patients with moderate to severely active RA despite an adequate course of MTX therapy were randomized to treatment with either resomelagon dosed at 60 mg, 80 mg, or 100 mg or with placebo once daily for 4 weeks as add-on treatment to stable background MTX treatment. In the Phase 2b portion of the RESOLVE study, patients will be randomized into up to 3 resomelagon dose groups or placebo, all administered once daily for 12 weeks as add-on treatment To stable background MTX treatment. The total study population may be up to 300 patients, depending on the number of dose groups of resomelagon selected for evaluation.

The objectives of the RESOLVE study are to evaluate the efficacy and safety of resomelagon vs placebo when added to background MTX therapy in DMARD-IR patients.