Summary of Rapport Therapeutics (RAPP) 2025 Conference Company Overview - **Company**: Rapport Therapeutics (RAPP) - **Industry**: Biotechnology, specifically in precision neuroscience and epilepsy treatment - **Key Personnel**: Abe Cisse (CEO), Choi Ignelzi (CFO) [1][2] Core Points and Arguments - **Vision**: Rapport aims to be a leading precision neuroscience company, focusing on receptor associated proteins to develop targeted therapies [4][5]. - **Lead Program**: RAP-two 19, an AMPA TARP gamma-eight modulator, targets specific brain areas to modulate AMPA receptors, aiming to reduce adverse effects (AEs) associated with traditional anti-seizure medications [5][6]. - **Clinical Trials**: - Currently conducting a Phase 2a proof of concept study for RAP-two 19 in focal epilepsy, fully enrolled with 30 patients, with data expected in September 2025 [7][8]. - Plans to explore RAP-two 19 in bipolar mania and peripheral neuropathic pain, with a long-acting injectable formulation also in development [8][9][10]. - **Differentiation**: RAP-two 19 is designed for once-daily dosing with a long half-life, aiming to minimize drug-drug interactions (DDIs) and improve patient adherence [12][14][15][16]. Important Data and Metrics - **Phase 1 Studies**: Completed four studies with 100 healthy volunteers, showing a favorable tolerability profile and high receptor occupancy (up to 85%) without significant sedation or motor impairment [23][24]. - **Efficacy Expectations**: The primary endpoint for the Phase 2a study is a 30% reduction in long episodes of seizures, with a target responder rate of at least 40% [38][39]. - **Safety Profile**: No serious adverse events (SAEs) reported; mild AEs observed were transient and resolved on their own [45][46]. Additional Insights - **Biomarker Utilization**: The study leverages an implantable RNS device to capture EEG activity, providing an objective measure of efficacy compared to traditional seizure diaries [28][30]. - **Regulatory Pathway**: The company plans to conduct two registrational trials for NDA submission, with the potential to start in 2026 [51][52]. - **Market Positioning**: The combination of efficacy, tolerability, and administration profile positions RAP-two 19 as a potentially best-in-class therapy for epilepsy [41][44]. Conclusion Rapport Therapeutics is advancing its lead program RAP-two 19 with a focus on precision neuroscience, aiming to address significant unmet needs in epilepsy treatment through innovative clinical trial designs and a differentiated safety profile. The upcoming data readout in September 2025 will be critical for the company's future development plans and market positioning.

Summary of Rapport Therapeutics Investor and Analyst Day Company Overview - **Company**: Rapport Therapeutics - **Event**: Inaugural Investor and Analyst Day - **Focus**: Lead candidate RAP-two 19 for epilepsy treatment Key Points and Arguments Industry and Product Focus - **Lead Candidate**: RAP-two 19, a TARP gamma eight AMPA modulator, aimed at treating focal onset seizures in epilepsy [3][19] - **Market Size**: Focal epilepsy affects approximately 1.8 million patients in the U.S., with 30-40% being drug-resistant [32] - **Pipeline**: Fully enabled pipeline including RAP-two 19 and two late-stage discovery programs targeting chronic pain and hearing disorders [19][27] Clinical Trials and Results - **Phase Two Trial**: Ongoing trial for RAP-two 19 in focal onset seizure patients, fully enrolled with results expected in September [21][26] - **Phase One Results**: Completed four Phase I studies with 100 healthy volunteers; RAP-two 19 was safe and well-tolerated [52][53] - **Receptor Occupancy**: Achieved target receptor occupancy of 50-70% at lower doses than predicted, indicating potential for effective treatment [56][58] Scientific Insights - **Mechanism of Action**: RAP-two 19 selectively modulates AMPA receptors in specific brain regions, potentially reducing side effects associated with traditional anti-seizure medications [38][39] - **Preclinical Efficacy**: Demonstrated significant efficacy in animal models with a favorable safety profile compared to existing treatments [44][46] Management and Strategy - **Management Team**: Comprised of experienced professionals in neuroscience and drug development, emphasizing a strategic approach to building the company [15][17] - **Vision**: To create a leading precision neuroscience company, addressing the limitations of conventional small molecules in treating neurological disorders [24][25] Additional Important Content - **Unmet Needs**: Despite numerous treatment options, the number of treatment-resistant epilepsy patients remains unchanged, highlighting the need for innovative therapies [92][93] - **Patient Population**: The trial population is representative of refractory focal epilepsy patients, enhancing the translatability of results to broader populations [87] - **Long-Acting Injectable**: Potential development of a long-acting injectable formulation for RAP-two 19, which could transform treatment for epilepsy patients [29][30] Conclusion Rapport Therapeutics is positioned to address significant unmet needs in the epilepsy treatment landscape with its innovative lead candidate RAP-two 19, backed by a robust clinical and scientific foundation. The company's strategic focus on precision neuroscience and the experienced management team further enhance its potential for success in the market.

Core Viewpoint - Rapport Therapeutics is advancing its Phase 2a trial of RAP-219 in refractory focal epilepsy, which is fully enrolled and expected to report topline results in September 2025, marking a significant milestone for the company and its precision neuroscience approach [3][4][10] Group 1: Clinical Trial Updates - The Phase 2a trial of RAP-219 is designed with input from leading epilepsy experts and utilizes intracranial electroencephalography (iEEG) data to assess the drug's potential effect on long episodes (LEs), a biomarker correlated with clinical seizures (CSs) [4] - Preliminary baseline characteristics of the first 14 enrolled patients indicate that the trial population is representative of historical registrational refractory focal epilepsy trials, with a median age of 37 years and a balanced sex distribution of 7 females and 7 males [5][6] - The company anticipates providing detailed analyses of primary and secondary endpoints, treatment-emergent adverse events (TEAEs), and a consolidated safety summary from Phase 1 trials when topline results are reported [9][12] Group 2: Financial and Operational Insights - As of March 31, 2025, Rapport reported $285.4 million in cash, cash equivalents, and short-term investments, which are expected to support operations through the end of 2026 [10] - The company has conducted four Phase 1 trials involving 100 healthy volunteers, reinforcing RAP-219's differentiated tolerability profile [9][10] Group 3: Future Catalysts - Upcoming milestones include the topline readout for RAP-219 in focal epilepsy in September 2025, initiation of a Phase 2a trial in bipolar mania in Q3 2025, and updates on the diabetic peripheral neuropathic pain program in the second half of 2025 [13]

Rapport Therapeutics (RAPP) Conference Summary Company Overview - **Company**: Rapport Therapeutics - **CEO**: Abe Sisan, with over 20 years in the biotech sector, previously president of Cerevel Therapeutics [doc id='4'][doc id='5'] - **CFO**: Troy Nelzi, with extensive experience in finance and business development, raised approximately $5 billion for eight approved products [doc id='3'] Industry Focus - **Sector**: Biotech, specifically in neuroscience and anti-seizure medications - **Key Product**: RAP two one nine (RAP-219), a TARP gamma eight AMPA modulator targeting focal epilepsy [doc id='7'][doc id='10'] Core Scientific Insights - **Receptor Associated Proteins (RAPs)**: Critical for regulating receptor function and signal transduction, allowing for targeted modulation of AMPA receptors [doc id='6'][doc id='8'] - **Differentiation**: RAP-219 aims to achieve significant seizure suppression without common adverse effects like sedation or motor impairment, presenting a potentially unprecedented therapeutic index [doc id='10][doc id='11'] Clinical Development - **Preclinical Evidence**: High probability of success in translating preclinical findings to clinical efficacy in epilepsy, with RAP-219 showing significant efficacy across various models [doc id='12'] - **Phase 2a Trial**: Utilizing an RNS device for objective measurement of efficacy, focusing on long episodes as a biomarker for seizure activity [doc id='15][doc id='16'] - **Expected Outcomes**: Aiming for a 30% reduction in long episodes correlating with at least a 50% reduction in clinical seizures, with results expected in Q3 2025 [doc id='31][doc id='34] Community Engagement and Feedback - **Interest from KOLs**: Significant interest in the trial design and methodology, viewed as a step forward in drug development for epilepsy [doc id='26][doc id='27'] - **Data Presentation**: Recent presentations at the American Academy of Neurology meeting highlighted the predictive value of long episode reductions for clinical seizure outcomes [doc id='28][doc id='29] Future Directions - **Next Steps**: If data is positive, plans to move into parallel Phase 2b/3 registrational trials [doc id='35] - **Pipeline Expansion**: Plans to initiate studies for bipolar mania and neuropathic pain, with data expected in early 2027 for bipolar mania [doc id='40] Conclusion - Rapport Therapeutics is positioned to potentially transform the treatment landscape for epilepsy and other neurological conditions through its innovative approach to drug development and its focus on precision neuroscience [doc id='39]