Rapport Therapeutics Inc. (Nasdaq: RAPP) announced positive topline results from a Phase 2 clinical trial evaluating RAP-219 in adults experiencing acute mania associated with bipolar I disorder.
The randomized, double-blind and placebo-controlled study enrolled 253 adults in the United States. Participants received either 0.75 milligrams of RAP-219 once daily or a placebo for three weeks in an inpatient setting. Other bipolar-disorder treatments, anxiolytics and hypnotics were discontinued during screening, although protocol-defined rescue treatment with lorazepam was permitted.
The trial met its primary endpoint at Week 3. Patients receiving RAP-219 experienced a 15.4-point average reduction from baseline on the Young Mania Rating Scale, compared with a 12.3-point reduction for the placebo group.
That produced a statistically significant 3.1-point placebo-adjusted difference, with a p-value of 0.045. Although the result crossed the conventional threshold for statistical significance, it did so by a narrow margin and will require confirmation in larger Phase 3 studies.
The trial also met its prespecified secondary endpoint. RAP-219 produced a 0.4-point improvement over placebo on the Clinical Global Impression–Bipolar Version mania-severity scale, with a p-value of 0.024.
All 11 symptoms measured by the Young Mania Rating Scale improved numerically compared with placebo. Improvements in irritability, thought content, disruptive or aggressive behavior and sexual interest reached nominal statistical significance.
“RAP-219 has the potential to break that cycle with the first new mechanism of action for bipolar mania in decades,” CEO Abraham Ceesay said.
Rapport reported that treatment-emergent adverse events occurred in 51.6% of RAP-219 patients and 52.8% of placebo recipients. No severe treatment-emergent or serious adverse events were reported during the three-week treatment period.
Discontinuations caused by adverse events occurred in 3.2% of RAP-219 patients and 0.8% of placebo patients. Agitation occurred more frequently with RAP-219 than placebo, at 16.7% versus 9.4%, while nausea was reported in 5.6% and 1.6%, respectively. The safety analysis was based on an interim database lock, with additional follow-up data expected at a future medical meeting.
RAP-219 is an investigational small molecule designed to selectively inhibit AMPA-receptor activity associated with TARP gamma-8, a protein concentrated in specific regions of the brain. Rapport is also evaluating the candidate in focal-onset and generalized seizures.
The company plans to discuss the bipolar-mania results and Phase 3 trial design with the FDA during the first quarter of 2027. Two pivotal studies are expected to begin during the second half of 2027.
Rapport reported $436.1 million in cash, cash equivalents and short-term investments as of June 30, 2026. Its second-quarter net loss was $56.6 million, while research and development expenses reached $51.4 million. Management expects its capital to fund operations into the second half of 2029, although that projection depends on clinical-development costs and other assumptions.
Upcoming Catalysts
- Additional Phase 2 efficacy and safety data at a medical meeting
- End-of-Phase 2 meeting with the FDA in early 2027
- Final design details for the bipolar-mania Phase 3 program
- Initiation of two pivotal bipolar-mania trials in the second half of 2027
- Data from RAP-219’s ongoing epilepsy programs
Sources
- Rapport Announces Positive Phase 2 RAP-219 Results — October 20, 2026
- RAP-219 Bipolar-Mania Trial, NCT07046494 — ClinicalTrials.gov
- Rapport Form 10-Q for the Quarter Ended June 30, 2026 — SEC
- Rapport Second-Quarter 2026 Financial Results — SEC
Editorial Disclosure
This article is based entirely on publicly available information, including company announcements, SEC filings and the federal clinical-trial registry. The security discussed is Rapport Therapeutics Inc. (Nasdaq: RAPP). Biotech Stocks Daily has not received compensation from Rapport Therapeutics, its management, investor relations representatives or any third party for this specific article. Biotech Stocks Daily may have current or past paid business relationships with other companies, which do not influence the content or conclusions of this article. No staff member or principal of Biotech Stocks Daily holds a position in the security discussed at the time of publication.
Sources used include Rapport’s October 20, 2026 topline-results announcement, the ClinicalTrials.gov record for the bipolar-mania study, the company’s second-quarter results and its SEC Form 10-Q for the quarter ended June 30, 2026. The reported clinical findings are topline company results and have not been independently validated by Biotech Stocks Daily or reviewed in a complete peer-reviewed publication.
RAP-219 remains investigational and has not been approved by the FDA for bipolar mania, epilepsy or any other indication. The Phase 2 study’s statistically significant primary result was close to the conventional significance threshold, and results from one trial may not be reproduced in larger pivotal studies. The reported safety analysis was based on an interim database lock and may change following completion of follow-up and full analysis.
Rapport has no products approved for commercial sale and has not generated product-sales revenue. Financial information reflects the company’s position as of June 30, 2026. Rapport expects continued research and development expenses and operating losses. Its projected cash runway into the second half of 2029 is a forward-looking estimate that depends on clinical costs, development timelines and other assumptions.
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