Rapport Therapeutics Conference Call Summary Company Overview - Rapport Therapeutics is focused on precision neuroscience, leveraging receptor-associated proteins to enhance treatment efficacy and tolerability for patients [2][3] Key Programs - The lead program, RAP-219, is a TARP gamma-8 AMPA modulator, showing promising results in epilepsy and ongoing programs in bipolar mania [2][3] - RAP-219 has demonstrated a 78% median reduction in clinical seizure frequency and a 24% seizure freedom rate in a proof of concept study [11][12] FDA Engagement and Study Plans - The company plans to meet with the FDA by the end of 2025 for an end of phase two meeting, aiming to start phase three studies by Q3 2026 [4][5] - Two parallel registrational studies are planned, following a standard protocol for focal epilepsy [4][5] Safety and Efficacy Insights - The biological thesis focuses on modulating the AMPA receptor through TARP gamma-8, which is expressed in key brain structures related to focal seizures [6][8] - The tolerability profile from phase two data showed a 10% discontinuation rate, indicating best-in-class tolerability for anti-seizure medications [9] - Concerns regarding adverse events (AEs) related to psychiatric disorders were addressed, with no significant findings in their trials [10] Patient Population and Efficacy Expectations - The proof of concept study involved a highly refractory patient population, with 70% on three or four anti-seizure medications [16] - The efficacy results are expected to translate well into the broader phase three patient population, despite potential variability [18][13] Bipolar Mania and Other Indications - The company is exploring RAP-219 for bipolar mania, supported by the drug's mechanism targeting excitatory processes in the limbic structure [24][26] - Enrollment for the bipolar trial is progressing well, with data expected in 2027 [26] Market Opportunity - The potential market opportunity for RAP-219 in epilepsy is estimated to be multi-billion dollars, with expected utilization similar to existing treatments like Keppra [29] Upcoming Milestones - Key updates expected include the end of phase two meeting with the FDA, additional data analyses at AES in December 2025, and the initiation of phase three studies in 2026 [30][31] - The company has sufficient cash reserves, approximately $500 million, to fund operations through 2029 [32]

Core Insights - Rapport Therapeutics reported positive Phase 2a results for RAP-219, indicating a potential best-in-class profile for treating drug-resistant focal onset seizures with a nearly 78% median reduction in clinical seizures and seizure freedom in nearly 24% of patients [2][5] - The company has a strong financial position with approximately $269.4 million in net proceeds from a recent public offering, ending the quarter with $513.0 million in cash, which is expected to fund operations into the second half of 2029 [4][11] Business Highlights - The Phase 2a clinical trial of RAP-219 met its primary endpoints with high statistical significance, showing 85.2% of patients achieving a ≥30% reduction in long episodes [5] - The company plans to initiate two Phase 3 pivotal trials of RAP-219 in focal onset seizures in Q3 2026 and expects topline results from the bipolar mania trial in the first half of 2027 [4][6] - An open-label long-term safety trial for patients from the Phase 2a trial is planned to begin by the end of 2025 [5] Financial Results - For Q3 2025, the company reported a net loss of $26.9 million, compared to a net loss of $17.5 million in the same period last year [11] - Research and Development (R&D) expenses increased to $22.3 million from $15.5 million year-over-year, driven by clinical development costs [11] - General and Administrative (G&A) expenses rose to $7.7 million from $6.1 million, reflecting business growth [11] Cash Position - The company ended Q3 2025 with $513.0 million in cash, cash equivalents, and short-term investments, a significant increase from $260.4 million as of June 30, 2025 [11] - The cash runway is expected to support operations and capital expenditures into the second half of 2029 [11]

Core Insights - Rapport Therapeutics is a clinical-stage biotechnology company focused on developing small molecule precision medicines for neurological and psychiatric disorders [17] - The company reported a net loss of $26.7 million for Q2 2025, an increase from $18.1 million in the same period last year [14] - The company ended the quarter with $260.4 million in cash and equivalents, expected to fund operations through the end of 2026 [5][14] Business Highlights - The Phase 2a trial of RAP-219 for drug-resistant focal onset seizures is fully enrolled, with topline results expected in September 2025 [5][8] - A Phase 2 trial of RAP-219 in bipolar mania has been initiated, with topline results anticipated in the first half of 2027 [9] - Plans for a Phase 2a trial in diabetic peripheral neuropathic pain are being finalized, with an update expected in 2025 [10] Financial Results - Research and Development (R&D) expenses for Q2 2025 were $22.7 million, up from $15.7 million in the prior year [14] - General and Administrative (G&A) expenses increased to $6.8 million from $5.1 million year-over-year [14] - The company reported a net loss per share of $0.75 for Q2 2025, compared to $1.70 for the same period in 2024 [24] Clinical Development Updates - The Phase 2a trial of RAP-219 is designed to assess its effect on long episodes (LEs) in patients, with a primary endpoint of achieving a ≥30% reduction in LEs [6] - The trial population shows a concordance of 92% between long episodes and electrographic seizures, with patients experiencing an average of 51 long episodes per 28 days [6] - The company expects to analyze the proportion of patients achieving a ≥50% reduction in clinical seizures as a key secondary endpoint [6] Corporate Updates - Rapport hosted its inaugural Investor and Analyst Day on June 2, 2025, featuring presentations from key executives and discussions with leading epilepsy experts [11] - The company is committed to a disciplined approach in advancing its pipeline and delivering transformative treatments for patients [2]

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]