Rapport Therapeutics clocked its second Phase 2 win in 14 months for RAP-219—which the company is positioning as a potential pipeline-in-a-product—this time showing improvement in symptoms of bipolar mania.
Shares of Rapport Therapeutics spiked early Tuesday morning after the biotech’s lead candidate showed significant improvement in bipolar mania symptoms in a mid-stage trial.
The Phase 2 trial, which was studying RAP-219 in 253 adults with acute bipolar mania, “just hits,” with acceptable safety, Stifel analysts wrote in a note to investors Tuesday morning.
Indeed, the trial met its primary endpoint as treatment with RAP-219 led to a 3.1-point placebo-adjusted improvement at three weeks on a scale measuring symptoms of the illness, the biotech reported on Tuesday. The Young Mania Rating Scale—the most commonly used rating scale in mania research, according to Rapport—measures 11 core symptoms, including elevated mood, increased activity and energy.
Patients taking Rapport’s drug saw a 15.4-point reduction in symptoms while placebo comparators had a reduction of 12.3 points.
Stifel called the trial win a “clear positive” against a backdrop of low expectations, however noting that the 3.1pt effect-size “just met statistical significance (p=0.045) and was on the lower-end of the range that’s considered competitive with available drugs today (3-4pts).”
RAP-219 also succeeded on the pre-specified secondary endpoint, showing a statistically significant improvement in mania severity score versus placebo at week three on a scale reflecting a clinician’s overall judgment of symptom severity.
Equally important, Stifel said, is that “safety here actually looks pretty good.”
RAP-219 was well-tolerated, Rapport said, with no severe treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) observed over the treatment period.
“For people with bipolar disorder, the challenge isn’t just finding a treatment that’s efficacious. It’s finding one they can tolerate and stay on,” Rapport CEO Abraham Ceesay said in a prepared statement. “Side effects drive discontinuation, and discontinuation drives relapse. RAP-219 has the potential to break that cycle with the first new mechanism of action for bipolar mania in decades.”
Shares of the biotech shot up more than 25% to $35.88 in premarket trading on Tuesday—though they stabilized upon market open, with the stock trading down about 2%.
Rapport declared in its press release that the result is clinical proof-of-concept for RAP-219’s novel TARPγ8-selective mechanism in bipolar mania, adding that the data support moving the program into Phase 3 trials, which are expected to begin in the second half of 2027.
RAP-219 is a TARPγ8-specific AMPA receptor (AMPAR) negative allosteric modulator. Neuro-imaging studies in patients with bipolar disorder show that the hippocampus, a region of the brain in which TARPγ8 is expressed, exhibits abnormal activation and hyperactivity, according to Rapport’s website. On the other hand, TARPγ8 is minimally expressed in the hindbrain, where drug effects are often associated with intolerable adverse events, Rapport noted in its announcement. This gives RAP-219 the potential to provide “a differentiated profile as compared to traditional neuroscience medications.”
The positive topline readout for RAP-219 in bipolar mania continues a positive run for the asset. In September 2025, Phase 2a data in drug-resistant focal epilepsy exceeded analyst and Wall Street expectations, reducing seizures by almost 78%. Rapport shares jumped more than 180% on the news. A federal trials database lists two Phase 3 trials in this indication, one that kicked off last month and another in June.
“Rapport now has clinical proof-of-concept in an indication beyond epilepsy, which builds on RAP-219’s multi-blockbuster potential heading into a Phase 3 program in second half 2027,” William Blair analysts wrote on Tuesday.
Ceesay added in his statement that the two datasets show the asset “delivering on its potential as a pipeline-in-a-product with two indications that both represent multibillion dollar market opportunities.”
