Key Highlights

  • RAP-219 met both primary and secondary endpoints in a 253-patient Phase 2 acute bipolar mania trial
  • Week 3 placebo-adjusted YMRS reduction of 3.1 points reached statistical significance (p=0.045)
  • CGI-BP score improved 0.4 points over placebo (p=0.024), with zero severe or serious adverse events reported
  • $436.1 million in Capital extends runway into 2H 2029; FDA consultation planned Q1 2027 ahead of two Phase 3 studies in 2H 2027

Article

Rapport Therapeutics (NASDAQ: RAPP) reported that RAP-219, its lead glutamate-receptor-targeted candidate, achieved statistically significant results on both the primary and secondary endpoints of a Phase 2 trial in adults experiencing acute bipolar mania, setting up a planned move into late-stage development in 2027.

Trial Design and Results

The study enrolled 253 adults diagnosed with acute manic or mixed episodes associated with bipolar I disorder. By Week 3 of treatment, patients receiving RAP-219 showed a 3.1-point placebo-adjusted reduction on the Young Mania Rating Scale (YMRS), the standard clinician-rated measure of manic symptom severity used across bipolar disorder trials, with the result reaching statistical significance at p=0.045.

On the secondary endpoint, the Clinical Global Impressions-Bipolar scale (CGI-BP), Rapport Therapeutics (NASDAQ: RAPP) said RAP-219-treated patients recorded a 0.4-point improvement over placebo, at p=0.024 — a tighter statistical Margin than the primary endpoint result, which the company said reinforces consistency of the treatment effect across two independently rated outcome measures.

On safety, the trial recorded zero severe or serious adverse events among the 253 participants, a tolerability profile Rapport Therapeutics (NASDAQ: RAPP) is positioning as a potential point of differentiation in a bipolar mania market where sedation, weight gain and metabolic side effects have historically limited patient adherence to approved antipsychotic and mood-stabilizing therapies.

Capital Position and Regulatory Path Ahead

Rapport Therapeutics (NASDAQ: RAPP) said it holds $436.1 million in available capital, a balance the company expects will fund operations into the second half of 2029 and cover the costs of advancing RAP-219 through its next clinical and regulatory milestones without requiring near-term additional financing.

Management outlined a two-step path toward pivotal testing: an End-of-Phase 2 consultation with the US Food and Drug Administration scheduled for the first quarter of 2027, followed by the initiation of two separate Phase 3 trials in the second half of 2027, contingent on alignment with the agency over trial design, dosing and endpoint selection.

RAP-219 is designed to selectively modulate TARP γ-8, an AMPA-receptor auxiliary protein expressed in brain regions implicated in mood regulation, a mechanism Rapport Therapeutics (NASDAQ: RAPP) has positioned as distinct from the dopamine- and serotonin-pathway mechanisms that underpin the antipsychotic and anticonvulsant drug classes currently approved for acute bipolar mania.

Market Context

Bipolar I disorder affects a sizable share of US adults, and current standard-of-care treatments for acute mania — including atypical antipsychotics and certain anticonvulsants — are frequently associated with sedation, metabolic changes and other side effects that can complicate long-term use. Rapport Therapeutics (NASDAQ: RAPP) said the absence of severe or serious adverse events in the RAP-219 program, paired with the statistically significant YMRS and CGI-BP results, positions the candidate as a potential alternative mechanism of action for a patient population that providers say remains underserved by existing options.

For investors, the Week 3 Phase 2 data stand as the most advanced efficacy signal reported to date for RAP-219 in a mood-disorder setting, and Rapport Therapeutics (NASDAQ: RAPP) said the results will directly inform the dosing, patient-population and endpoint choices it brings to its planned FDA meeting before finalizing the design of its two-trial Phase 3 program.