Rapport’s Epilepsy Drug Data Signals a Precision Strike on Neurology

BOSTON, MA – December 05, 2025 – In the high-stakes world of biotechnology, data is currency. But for Rapport Therapeutics, the new clinical results unveiled today are more than just data; they are a declaration of intent. As the American Epilepsy Society (AES) Annual Meeting gets underway, the Boston-based company presented a post-hoc analysis of its Phase 2a trial for RAP-219 that suggests it has a potential market disruptor on its hands for drug-resistant focal onset seizures (FOS). The results go far beyond simple efficacy, painting a picture of a therapy that is not only powerful but also strategically differentiated in a crowded and challenging field.

While the topline results announced in September were already impressive—a 77.8% reduction in clinical seizures and seizure freedom for nearly a quarter of patients—the new analysis provides critical context that has investors and clinicians taking notice. The data shows RAP-219’s effects are both rapid and remarkably consistent over the entire eight-week treatment period. More importantly, it works effectively regardless of a patient's baseline disease severity and, in a crucial strategic differentiator, significantly improves patient-reported quality of life. This isn't just another anti-seizure medication; it's a precision tool designed to solve problems that have long plagued epilepsy treatment.

A New Paradigm in Precision Neuroscience

For decades, the development of anti-seizure medications (ASMs) has often been a blunt instrument affair. Many drugs work by broadly suppressing neuronal activity across the brain, which can reduce seizures but often comes at the cost of debilitating side effects like cognitive fog, dizziness, and fatigue. Rapport’s strategy with RAP-219 is a direct challenge to this paradigm.

The drug is a potential first-in-class negative allosteric modulator (NAM) that specifically targets the TARPγ8-associated AMPA receptor. This is the core of its disruptive potential. Unlike the AMPA receptors found throughout the central nervous system, the TARPγ8 protein is expressed with neuroanatomical precision, primarily in brain regions like the hippocampus and neocortex where focal seizures frequently originate. Crucially, it has minimal expression in areas like the hindbrain, which are often implicated in the intolerable side effects of less targeted drugs.

This “precision neuroscience” approach is the “why” behind the promising clinical profile. By targeting only the specific receptor complexes implicated in seizure generation, RAP-219 aims to deliver potent efficacy exactly where it's needed while sparing the rest of the brain. The result, as seen in the Phase 2a trial, is a drug that was generally well-tolerated, with a low 10% discontinuation rate despite its powerful effect on seizures. This combination of targeted power and improved tolerability is the holy grail in neurology and represents a significant competitive advantage over existing therapies.

Beyond Seizure Counts: Redefining Clinical Success

Perhaps the most compelling aspect of the new data is its focus on what matters most to patients: their quality of life. For the millions living with drug-resistant epilepsy, the impact of the disease extends far beyond the seizures themselves. The post-seizure recovery period, cognitive disruption, and interference with daily activities can be just as devastating. Rapport’s analysis directly addresses this unmet need.

The data, derived from the Seizure Severity Response Questionnaire (SSRQ), showed that patients treated with RAP-219 experienced statistically significant improvements in key domains. Patients reported a 75% median decrease in overall seizure intensity, a 71.4% improvement in their ability to think or concentrate after a seizure, and a remarkable 94.4% reduction in the seizure's interference with daily activity.

This is a strategic masterstroke. By quantifying these patient-centric benefits, Rapport is changing the conversation around what defines a successful epilepsy treatment. It’s no longer just about the number of seizures on a chart; it’s about giving patients their lives back. This aligns perfectly with the priorities of patient advocacy groups, which have long called for therapies that do more than just manage symptoms. Demonstrating a tangible impact on daily function and recovery could be a key factor in driving adoption and securing favorable market access if RAP-219 reaches commercialization.

The Strategic Blueprint for Market Leadership

The positive clinical data is fueling a well-defined strategic push toward market entry. The company has announced plans for an end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) this quarter, a critical step to align on the design of registrational trials. Rapport is targeting the third quarter of 2026 to initiate two pivotal Phase 3 studies, an ambitious but achievable timeline that signals strong confidence from management.

This confidence is being echoed by the market. In the weeks leading up to the AES presentation, analysts have been bullish, with firms like BTIG and Truist initiating coverage with “Buy” ratings and price targets suggesting significant upside. Rapport’s stock (Nasdaq: RAPP) has responded in kind, reflecting growing investor belief that the company is on a clear trajectory to capitalize on its lead asset. This positive sentiment is crucial, as it strengthens the company's financial position ahead of the costly Phase 3 program.

“These additional results build upon the robust efficacy data we observed in the Phase 2a trial and further expand the growing body of evidence supporting RAP-219’s potential as a best-in-class anti-seizure medication,” said Jeffrey Sevigny, M.D., chief medical officer of Rapport, in the company’s press release. The statement underscores the company’s belief that it has not just a viable drug, but a category leader.

A Pipeline Within a Product

Rapport’s strategic vision extends well beyond focal onset seizures. The company views RAP-219 as a “pipeline-in-a-product,” leveraging the unique biology of TARPγ8 to explore other neurological and psychiatric disorders where this target may be relevant. A Phase 2 trial in bipolar mania is already enrolling patients, with results expected in 2027, and plans for a Phase 2 trial in diabetic peripheral neuropathic pain are expected to be updated early next year. This multi-indication strategy diversifies risk and vastly expands the drug's long-term commercial potential.

Furthermore, Rapport is demonstrating shrewd lifecycle management by developing a long-acting injectable (LAI) formulation of RAP-219. Nonadherence to daily oral medications is a major cause of treatment failure and breakthrough seizures in epilepsy. An LAI formulation could dramatically improve patient outcomes by ensuring consistent drug levels, providing a durable competitive advantage and expanding the drug’s clinical utility. This forward-thinking approach shows that Rapport is not just focused on getting a drug approved, but on building a sustainable franchise that can dominate the market for years to come. The journey from lab to market is long, but with RAP-219, Rapport Therapeutics has drawn a clear map for disrupting the neurology landscape.