SynAct Pharma (SYNACT) Study Result summary

EXPAND efficacy

• Phase 2b trial randomized 127 treatment-naïve patients with high-activity RA to 12 weeks of resomelagon 100 mg plus MTX or placebo plus MTX.

• Primary endpoint was not met: week-12 ACR20 response was 54.7% with resomelagon vs 55.7% with placebo (treated n=53 vs 61).

• Tender and swollen joint-count reductions appeared in line with BEGIN and favored resomelagon; patient and investigator assessments did not reflect those reductions.

• High placebo response and substantial between-site variability, driven mainly by subjective measures, likely limited treatment discrimination.

Safety and tolerability

• Over 12 weeks, serious TEAEs occurred in 1.6% of each group; no TEAEs led to death, and no severe TEAEs were recorded.

• TEAEs leading to study discontinuation occurred in 7.9% with resomelagon vs 1.6% with placebo; at least one TEAE occurred in 42.2% vs 44.4%.

• The top-line update characterized the safety profile after 3M therapy as very favorable.

Interpretation and further analysis

• ACR response requires improvement in tender and swollen joints plus improvement in 3 of 5 other measures; four of those measures are subjective.

• Subjective assessment in EXPAND differed markedly from BEGIN, while objective parameters were more consistent with BEGIN.

• Further analysis of the full EXPAND dataset was planned after release of top-line results.