SynAct Pharma AB reported additional data from the 12-week P2b EXPAND study of 100mg once- daily oral resomelagon (AP1189) in newly diagnosed rheumatoid arthritis (RA) patients experiencing severe disease activity. SynAct previously announced that the study did not meet the primary endpoint of a significantly higher ACR20 response at 12 weeks as compared to placebo. This release identifies a patient population with active systemic inflammation, where resomelagon demonstrated activity over placebo on the ACR20 primary endpoint as well as all other assessed secondary outcome measures.

SynAct management will hold a webcast to discuss this announcement later (details below). The EXPAND (SynAct-CS007) study was a multicenter, randomized, double-blind, placebo- controlled, 12-week study in newly diagnosed, treatment naïve patients with highly active RA (Clinical Disease Activity Score (CDAI) > 22) conducted in sites in Bulgaria and Moldova. 127 patients presenting with high disease activity (CDAI > 22) were randomized 1:1 for treatment with once daily 100 mg resomelagon or placebo added to a background of methotrexate (MTX) therapy.

In patients with baseline CRP levels of >3mg/L (c-reactive protein, a blood marker of systemic inflammation, 61% of the full study population), resomelagon demonstrated consistent activity over placebo with 70.6% of resomelagon treated patients achieving an ACR20 response at 12weeks compared to 54.3% of patients on placebo. Similar strong trends favoring resomelagon treatment were seen across the individual ACR component scores as well as other key secondary outcome measures including reduction in Clinical disease activity index (CDAI) and disease activity evaluated by Disease Activity Score (DAS28). The HAQ score, a self-assessment of patient physical ability that is a component of ACR scoring, demonstrated at 12 weeks that resomelagon treated patients achieved a 60% higher improvement over placebo treatment.

This assessment adds to the previously announced favorable safety and tolerability profile of resomelagon. Resomelagon (AP1189), is a once-daily oral selective 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 cell types 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 EXPAND (SynAct-CS007) study is a multicenter, randomized, double-blind, placebo-controlled, 12-week study in newly diagnosed, treatment naïve patients with highly active RA (Clinical Disease Activity Score (CDAI) > 22) In EXPAND, 127 RA patients with high disease activity (CDAI > 22) were randomized 1:1 for treatment with either 100 mg resomelagon (AP1189) tablets or placebo tablets for a once daily dose for 12 weeks, concurrently with the initiation of dosing with methotrexate.

The primary efficacy read-out in the EXPAND is proportion of patients achieving 20% improvement in ACR (ACR20) at week 12 relative to placebo. The safety evaluation included adverse event monitoring, biochemical and hematological evaluation, physical examinations, and vital sign measurements. In addition, several secondary efficacy endpoints are defined, including, ACR50, ACR70, CDAI, and Disease activity score 28 (DAS-28) change over time, Change in Health Assessment Questionnaire ­ Disability Index (HAQ-DI) and Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue), as well as use of corticosteroids as rescue medication.

Tertiary endpoints are included to further explore the effect of resomelagon (AP1189) on biomarkers and by evaluation of synovial inflammation using magnetic resonance imaging (MRI).