Summary of Rapport Therapeutics Conference Call Company Overview - **Company**: Rapport Therapeutics - **Focus**: Developing precision neuroscience therapeutics, particularly for focal epilepsy with lead program RAP219 [1][2] - **Background**: Company spun out from technology developed by Dr. David Brett, with a history at UCSF and Eli Lilly [3] Key Points Financials and Development Timeline - **Public Offering**: Company went public in June of the previous year [3] - **Cash Position**: Ended the year with approximately $285 million, sufficient to fund operations through at least the end of the next year [4] - **Upcoming Milestones**: - Phase two trial readout for focal onset patients expected in Q3 [4] - Initiation of bipolar mania trial in Q3 with data expected in early 2027 [4] Scientific Approach - **Technology**: Focus on receptor-associated protein technology to target specific areas in the brain, enhancing drug precision [3] - **Lead Program**: RAP219 targets AMPA receptors through the accessory protein gamma-eight TARP, aiming to reduce side effects associated with non-selective targeting [5][8] - **Preclinical and Phase One Data**: - Strong preclinical data supporting the targeting approach, with a focus on receptor occupancy and therapeutic index [14][15] - Phase one PET study confirmed receptor occupancy exceeding 80% at therapeutic concentrations [15][17] Clinical Trial Design - **Innovative Trial Design**: - Utilizes an RNS device to track long episodes of epileptic activity, providing objective data [20][25] - Aims to correlate long episode frequency with clinical seizure frequency, with a target of a 30% decrease in long episodes correlating with a 50% decrease in clinical seizures [34] - **Success Metrics**: - Aiming for a responder rate of 40% or greater in the trial participants [36] - Combination of clinical seizure diary data and objective electrographic biomarkers to validate findings [39] Market Opportunity - **Focal Epilepsy Market**: Approximately 1.8 million patients with focal epilepsy, with 40% still experiencing seizures, indicating a significant market opportunity for new treatments [49] - **Pipeline Potential**: Plans to initiate a phase two study in bipolar disorder, leveraging the mechanism of action that targets hyperactivity in the limbic system [50][51] Additional Insights - **Community Engagement**: The trial design was influenced by feedback from the medical community, emphasizing the need for more efficient and predictive drug development methods [21][30] - **Regulatory Perspective**: The FDA is seen as potentially supportive of the innovative trial design, although it remains early in the process [45] This summary encapsulates the key aspects of the conference call, highlighting the company's strategic direction, scientific innovations, and market potential.