Rapport Therapeutics (RAPP) Study result summary

Study design and endpoints

• Randomized, double-blind Phase 2 trial enrolled 253 adults with bipolar I acute mania, including patients with mixed or psychotic features; 126 received RAP-219 0.75 mg and 127 placebo for 21 days, followed by an eight-week safety follow-up.

• Primary endpoint was placebo-adjusted change in YMRS at Week 3; the secondary endpoint was change in CGI-BP mania severity.

Efficacy

• Primary endpoint met: Week 3 YMRS improved 15.4 points with RAP-219 versus 12.3 with placebo, a 3.1-point placebo-adjusted difference (p=0.045).

• Secondary endpoint met: Week 3 CGI-BP mania severity improved 0.4 points versus placebo (p=0.024).

• All 11 YMRS items numerically favored RAP-219; irritability, thought content, disruptive-aggressive behavior, and sexual interest were nominally significant at Week 3.

• Placebo-adjusted YMRS improvement increased from 0.9 points at Week 1 to 2.2 at Week 2 and 3.1 at Week 3; irritability and disruptive-aggressive behavior were also nominally significant at Week 2.

Safety and tolerability

• TEAEs occurred in 51.6% of RAP-219 participants versus 52.8% with placebo; psychiatric TEAEs occurred in 34.9% versus 33.1%.

• All TEAEs were mild or moderate; no severe TEAEs or SAEs occurred on treatment.

• TEAE-related discontinuations were 3.2% with RAP-219 versus 0.8% with placebo.

• Agitation was the most common RAP-219 TEAE (16.7% vs 9.4% with placebo), usually arising in Week 1; somnolence and dizziness were low, with no akathisia or extrapyramidal symptoms reported.