📄 What This Document Is 📰

This filing is a detailed summary of results presented at a major medical conference, the 2026 American Academy of Neurology (AAN) Annual Meeting. It's not a formal SEC filing, but an official presentation of scientific data about the company's lead drug, RAP-219.

Because this document presents clinical trial data, it is highly important for investors, as it shows how well the drug may work in real patients. The core focus is demonstrating sustained efficacy and favorable safety profile for treating Focal Onset Seizures (FOS) far beyond the initial treatment period.

👉 The Headline: Rapport Therapeutics is presenting strong, sustained anti-seizure data for RAP-219, suggesting the drug remains effective even after the treatment drug has been stopped.

🏢 What The Company Does 🧠

Rapport Therapeutics is a clinical-stage biotechnology company that specializes in discovering and developing small molecule precision medicines. They focus specifically on patients suffering from neurological and psychiatric disorders.

In simple terms, the company uses a unique technology platform to target specific proteins in the brain. Their founders made pioneering discoveries related to Receptor Associated Proteins (RAPs), which form the basis of their science.

👉 The Strategy: Instead of designing drugs that affect the entire brain (which often leads to side effects), Rapport's approach selectively targets proteins found only in specific, small brain regions—the areas where certain seizures often start.

🔬 The Science Behind RAP-219 🧬

The drug, RAP-219, is an investigational and potential first-in-class medicine. It belongs to a class of drugs called Negative Allosteric Modulators (NAMs).

The drug works by targeting a protein called TARPγ8, which is expressed only in discrete brain regions like the hippocampus and neocortex. These are the exact spots where the company believes focal seizures frequently originate.

• Why it matters: By using this "precision approach," Rapport hopes to offer a medicine that is highly effective at the source of the seizure while minimizing effects on other parts of the brain where the protein is not found. This could lead to a more differentiated profile compared to older epilepsy medications.

📊 Key Clinical Efficacy Results 💡

The company presented results from the follow-up period of its Phase 2a trial. This data is compelling because it shows the drug's effect after the active treatment period is over.

The trial tracked patients for 8 weeks of treatment, followed by an 8-week observation period (Weeks 9–16) to see if the benefits lasted. The results showed strong anti-seizure effects throughout the entire 16 weeks.

• Long Episodes (LEs): During the follow-up period (Weeks 9–12), RAP-219 showed a median reduction of 80% in LEs compared to baseline. This continued through the second half of follow-up (Weeks 13–16) with a 68% median reduction.
• Clinical Seizures: The median reduction in clinical seizures was particularly high in the first four weeks of follow-up, showing a 90% reduction. This was followed by a sustained, clinically meaningful 59% median reduction in the second four-week follow-up period.
• Overall Impact: Across the full 16-week period, patients experienced a 69% median reduction in LEs and a 68% median reduction in clinical seizures compared to baseline.

👉 Why it matters: Showing sustained improvement months after dosing stops is a major breakthrough. It suggests the drug's positive effect is lasting, not just temporary.

🕒 Pharmacokinetics and Safety 🛡️

The study also provided critical details about how the drug moves through the body and how safe it is to use.

Drug Longevity (Half-Life):

• The company revised its estimate of RAP-219’s half-life (the time it takes for the drug concentration to drop by half) to approximately 22 days. This is an increase from a prior estimate of 14 days.
• Why it matters: A longer half-life is excellent for patients because it means the drug stays in the body for a longer time, potentially allowing for less frequent dosing.

Tolerability and Adverse Events:

• RAP-219 was generally well tolerated throughout the 16-week follow-up period.
• The adverse event data was mild: two patients had mild (Grade 1) treatment-related adverse events, and three patients had serious adverse events (SAEs); however, none of the SAEs were considered by the investigator to be related to the drug.

🔬 Analyzing Broader Treatment Periods 🔎

The presentation provided comprehensive data spanning different time frames, giving a full picture of the drug's potential.

The data included analyses covering the full 16 weeks and also the first 12 weeks. For instance, when looking at the full 16-week window, patients showed a median reduction of 68% in clinical seizures.

This deep dive into multiple time anchors shows that the drug's efficacy metrics (like the median percent reduction in LEs and clinical seizures) remained stable and impressive even when looking at the combined treatment and follow-up period.

🚀 Future Pipeline and Development Plans 🗓️

Rapport is not focusing only on Focal Onset Seizures. The company has a robust pipeline of potential treatments and clear development milestones planned for the near future.

• Primary Focus (FOS): Two pivotal Phase 3 trials—named FOCUS 1 (RAP-219-FOS-301) and FOCUS 2 (RAP-219-FOS-302)—are expected to kick off in the second quarter (Q2) of 2026.
• Long-Term Safety: An open-label long-term safety trial (OLE) is currently running, with initial data expected in the second half of 2026.
• Other Indications: Outside of FOS, the company is advancing RAP-219 into other areas:
  • Bipolar Mania: Phase 2 results are expected in the first half of 2027.
  • Primary generalized tonic-clonic seizures: A Phase 3 trial is expected to begin in the first half of 2027.
• Delivery Method: They are also developing a long-acting injectable (LAI) formulation of RAP-219, with Phase 1 initial PK results anticipated in 2027.

👉 What this means: This roadmap signals a rapid and focused progression toward commercial potential, spanning multiple seizure types and treatment delivery methods.

🎙️ Expert Commentary and Management Outlook ✨

The chief medical officers spoke highly of the data, emphasizing both the scientific significance and the clinical benefit of these long-term results.

• William Motley, M.D. (RAP-219 program leader) stated: "Clinical outcomes improved further during the first four weeks after dosing ended, highlighted by a 90% reduction in clinical seizures, and consistent with the observed PK. These data demonstrate RAP-219’s treatment effect in focal onset seizures out to 16 weeks of therapeutic drug exposure and furthermore show a consistent dose-exposure-clinical outcome relationship that provides us confidence in the doses we’re advancing in Phase 3 trials.”

  • Interpretation: This quote directly links the drug's physical presence (pharmacokinetics/dose) to the clinical result, giving the company strong confidence in their dosing strategy for future, larger trials.

• Jeffrey Sevigny, M.D. (Chief Medical Officer) remarked: "We believe these follow-up period results underscore the sustained activity of RAP-219 beyond the 8-week treatment period. Together with the treatment period data, these findings further support our view that RAP-219 has the potential to become a differentiated, best-in-class therapy and an important new treatment option for patients with focal onset seizures.”

  • Interpretation: This statement sets a high bar for the drug, declaring its potential to be a leading, unique (best-in-class) therapy in the field.

📞 Getting More Information 📬

If you want to follow up on the company’s progress or get further financial information, the key contact is:

• Julie DiCarlo, Head of Communications & IR
• Email: [email protected]

---

🧠 The Analogy

Think of RAP-219 like turning down the sound on a very specific, loud speaker in one room of a massive theater. Most traditional anti-seizure drugs are like putting bubble wrap all over the entire theater (affecting everywhere, causing side effects). Rapport’s drug, however, is like surgically isolating that single faulty speaker (TARPγ8 in the hippocampus) and silencing it specifically, leaving the rest of the theater (the brain) undisturbed.

🧩 Final Takeaway

Rapport Therapeutics presented compelling Phase 2a data demonstrating that RAP-219 provides sustained, high-level seizure reduction (up to 90% reduction in clinical seizures) 16 weeks after treatment started. With major Phase 3 trials scheduled for Q2 2026, the company is positioning itself for a best-in-class role in the epilepsy market.