Rapport Therapeutics Conference Call Summary Company Overview - **Company**: Rapport Therapeutics (NasdaqGM:RAPP) - **Event**: FY Conference on September 17, 2025 Industry Context - **Industry**: Neuropsychiatry and Epilepsy - **Market Size**: Approximately 1.8 million patients in the U.S. with 560,000 treatment-resistant patients [2][27] Key Points and Arguments Phase 2 Trial Results - **Efficacy**: The Phase 2 trial demonstrated a median reduction of 78% in clinical seizures and a 24% seizure freedom rate, indicating a best-in-class profile for the anti-seizure medication RAP-219 [5][26] - **Patient Demographics**: The trial enrolled treatment-resistant focal epilepsy patients, with 70% on three or four anti-seizure medications, confirming the refractory nature of the population [7][8] - **Trial Design**: The trial utilized a novel design informed by the epilepsy community, leveraging an electrographic biomarker to predict clinical seizure reductions [4][9] Next Steps - **Phase 3 Plans**: Rapport Therapeutics plans to initiate two parallel Phase 3 studies in Q3 2026, following an end of Phase 2 meeting with the FDA [10][36] - **Translatability**: The results from the Phase 2 trial are believed to be highly translatable to registrational studies, improving the probability of success [6][9] Safety and Tolerability - **Tolerability Profile**: The trial reported a 10% discontinuation rate, one of the lowest in proof of concept studies for this patient population, with no severe adverse events greater than grade two [18][24] - **Comparison with Other Drugs**: RAP-219 showed a differentiated tolerability profile compared to Fycompa, with significantly lower rates of sedation and aggression [19][22] Commercial Potential - **Market Opportunity**: The peak sales opportunity for RAP-219 has shifted from an estimated $1.5 billion to potentially much higher, with expectations of broad adoption by general neurologists and internists [26][27] - **Long-Acting Injectable**: There is potential for developing a long-acting injectable formulation, which could transform patient management in epilepsy [29][30] Future Indications - **Bipolar and Pain**: The Phase 2 results have raised the probability of success for other indications like bipolar mania, due to confirmed target engagement and a favorable tolerability profile [39][40] Financial Position - **Cash Balance**: As of Q2, the company had $260 million, sufficient to fund operations through the end of 2029, including the initiation of Phase 3 trials and development of a long-acting injectable [37][38] Additional Important Insights - **Community Feedback**: The company has received positive feedback from the epilepsy community regarding the drug's profile and potential for adoption [26][28] - **Enrollment Strategy**: The company is focused on enrolling the right patient population for Phase 3 studies, considering competitive context and drug profile [32][33] This summary encapsulates the critical insights from the conference call, highlighting the promising developments for Rapport Therapeutics and its lead candidate RAP-219 in the epilepsy market.