Question-and-Answer SessionBut maybe without doing too much background Abe, you could just sort of set the stage on where the company is at. And I think it would be good too, to set the stage on the 219 pivotal program in epilepsy and where things are going there. So I'll let you take it away. Thank you.Abraham CeesayCEO, President, Treasurer & Director Sure. Thanks, Paul, and good morning, everyone. I appreciate the opportunity. So 2025 was truly a foundational and transformational year for us at Rapport. ...

Mise à disposition des éléments préparatoires à l'AG du 27/03/2026 - Rapport Financier Annuel 2025 March 12, 2026 03:00 ET  | Source: Credit Agricole de la Touraine et du Poitou Credit Agricole de la Touraine et du Poitou ...

Rapport Therapeutics Conference Call Summary Company Overview - **Company**: Rapport Therapeutics (NasdaqGM:RAPP) - **Focus**: Precision neuroscience, specifically targeting receptor-associated proteins related to AMPA receptors, which are crucial in the treatment of epilepsy [2][4] Key Points and Arguments Unique Mechanism of Action - Rapport Therapeutics is developing RAP-219, which targets TARP gamma 8, an auxiliary protein associated with AMPA receptors, selectively expressed in brain regions critical for focal-onset seizures [3][4] - This selectivity allows for a higher therapeutic index compared to traditional anti-seizure medications, which often have low therapeutic indices and significant side effects [4][10] Clinical Data and Efficacy - The company reported a **72% reduction** in long episodes of electrographic seizures and a **78% median reduction** in clinical seizures during their proof of concept study [13] - A **24% seizure freedom rate** was observed from day 1 to day 56 in the trial [14] - The innovative use of the RNS System for continuous monitoring of electrographic activity allowed for a more efficient study design, reducing the required sample size to 30 patients [16][12] Tolerability Profile - RAP-219 demonstrated a favorable tolerability profile with a **10% discontinuation rate**, which is low for focal epilepsy trials [30] - Common adverse events included dizziness and headache, typical of anti-seizure medications, but were generally mild to moderate [30] Phase 3 Study Plans - Two parallel Phase 3 studies are set to begin in Q2 2026, exploring different dosing strategies (0.25 mg and 0.75 mg in one study, 0.75 mg and 1.25 mg in another) [41] - The studies aim to confirm the efficacy seen in Phase 2 and will include a titration schema over 7-9 days [42] Strategic Partnerships and Market Position - A partnership with Tenacia in China was established, providing a **$20 million upfront payment** and potential for **$308 million in biobucks** and royalties, which will support development in the region [53] - The partnership allows for patient recruitment in China, which has historically been inaccessible for such trials [52] Future Indications and Pipeline - The company plans to expand RAP-219's indications to include primary generalized tonic-clonic seizures and is also exploring its use in bipolar mania, with data expected in 2027 [111][112] - The long-acting injectable (LAI) formulation of RAP-219 is in development, with potential human PK results expected in 2027, which could transform treatment options for epilepsy patients [93][94] Financial Outlook - Rapport Therapeutics has sufficient cash runway into the second half of 2029, allowing for the completion of ongoing studies and the initiation of new trials [121] Additional Important Insights - The company believes that the unique mechanism and efficacy of RAP-219 could position it as a best-in-class therapy for focal-onset seizures [81][88] - The potential for a long-acting injectable formulation could address significant patient needs and extend the revenue durability of the product [96][100] This summary encapsulates the key points discussed during the conference call, highlighting the innovative approach of Rapport Therapeutics in the epilepsy treatment landscape and its strategic plans for future growth and development.

Rapport Therapeutics Conference Call Summary Company Overview - **Company**: Rapport Therapeutics (NasdaqGM:RAPP) - **Focus**: Development of a novel drug for epilepsy treatment, specifically RAP-219, which is advancing from phase 2 to phase 3 trials [1][2] Core Points and Arguments Drug Mechanism and Efficacy - **Target**: RAP-219 is a TARP gamma-8 AMPA modulator, focusing on four brain structures to treat focal onset seizures and bipolar mania [3] - **Efficacy**: Preclinical models showed unprecedented efficacy in controlling seizures without significant adverse effects, unlike existing pan-AMPA antagonists [5][11] - **Clinical Data**: Phase 2 trial demonstrated a 78% median reduction in clinical seizures and a 72% reduction in electrographic seizures, surpassing initial expectations of 50% and 30% respectively [19][31] Safety Profile - **Tolerability**: The drug exhibited a low discontinuation rate of 10%, with all adverse events being mild to moderate, and no serious adverse events reported [21] - **Therapeutic Index**: The drug maintains a wide therapeutic index, which is crucial for its safety and efficacy [13] Trial Design and Execution - **Phase 3 Trial**: The design will include two parallel studies with approximately 330 subjects each, focusing on low-medium and mid-high dose strategies [24][25] - **Global Collaboration**: A partnership with Tenacia in China aims to enhance global development and patient enrollment for the phase 3 trials [27] Market Opportunity - **Target Population**: 30%-40% of the 1.8 million patients with focal onset seizures are refractory to current treatments, representing a significant market opportunity [30] - **Market Size**: The potential market for branded drugs in this segment is estimated at $15 billion [31] Additional Indications - **Bipolar Mania**: The drug is also being studied for bipolar mania, leveraging its mechanism to reduce glutamate transmission, which is implicated in the disorder [36][37] - **Tonic-Clonic Seizures**: Plans to initiate a phase 2 study for tonic-clonic seizures based on positive results from focal onset studies [39] Long-Acting Injectable Development - **Differentiation**: RAP-219 is being developed as a long-acting injectable (LAI), which is uncommon for anti-seizure medications. Its potency, low solubility, and long half-life make it suitable for this formulation [42][44] - **Market Impact**: The LAI could extend exclusivity and revenue durability, appealing to both patients and physicians [47] Conclusion - Rapport Therapeutics is positioned to make significant advancements in the treatment of epilepsy and bipolar disorder with its innovative drug RAP-219, backed by strong clinical data and a clear market strategy. The ongoing development of a long-acting injectable formulation further enhances its potential impact in the market [50]

Drug Development and Trials - Company is developing RAP-219, a precision small molecule designed to target TARP8 for treating focal onset seizures (FOS) and other neurological disorders [20]. - Phase 2a trial of RAP-219 in drug-resistant FOS showed statistically significant reduction in long episodes and clinical seizures compared to baseline over an 8-week period [22]. - Company plans to initiate Phase 3 trials for RAP-219 in FOS in Q2 2026 and in primary generalized tonic-clonic seizures (PGTCS) in H1 2027 [22][23]. - RAP-219 is also being evaluated for potential treatment of bipolar mania, with topline results expected in H1 2027 [24]. - Company has initiated IND-enabling activities for RAP-641, a candidate targeting the α6β4 nicotinic acetylcholine receptor for chronic pain and migraine [39]. - The α9α10 nicotinic acetylcholine receptor program is focused on therapies for hearing and vestibular disorders, with small molecule modulators being optimized for clinical advancement [40]. - RAP-219 is advancing to Phase 3 clinical development for Focal Onset Seizures (FOS), with initiation planned for Q2 2026 following FDA meetings [46]. - Following the successful Phase 2a trial, the company plans to initiate two parallel Phase 3 trials of RAP-219 in drug-resistant focal onset seizures in Q2 2026 [102]. - The Phase 3 program will include two trials enrolling over 300 adults each, evaluating RAP-219 over a 14-week treatment period [104]. - The Phase 2a proof-of-concept trial enrolled 30 participants, with 86.7% completing dosing; primary reasons for discontinuation were adverse events [96]. Market Potential and Patient Demographics - The total branded market for epilepsy is projected to grow from approximately $2.8 billion in 2022 to $3.6 billion by 2028 [32]. - Approximately 30 to 40 percent of epilepsy patients experience drug-resistant seizures despite taking two or more antiseizure medications [34]. - Epilepsy affects approximately 50 million people globally, with 3 million adults in the U.S., and the annual direct costs in the U.S. are estimated at $28 billion [54]. - Focal Onset Seizures account for 60% of all epilepsy cases, with an estimated 1.8 million patients in the U.S. affected [61]. - Approximately 0.8 million patients in the U.S. experience Primary Generalized Tonic-Clonic Seizures (PGTCS), representing 25%-35% of all epilepsy patients [105]. - Bipolar disorder affects 2.8% of the adult U.S. population, equating to approximately 7.2 million adults [109]. - The global bipolar disorder market was approximately $1.4 billion in 2022, expected to grow to over $4 billion by 2028 [109]. Drug Efficacy and Safety - RAP-219 demonstrated a half maximal effective concentration (EC50) of 2.3 ng/mL in preclinical models, indicating its potency [70]. - The drug showed no motor impairment in preclinical tests, suggesting a favorable therapeutic index compared to traditional ASMs [70]. - In the Phase 2a trial, 85.2% of patients achieved a ≥30% reduction in long episodes (LEs) from baseline (p<0.0001), and 72.0% achieved a ≥50% reduction in clinical seizures (p<0.0001) [97]. - The median reduction in LE frequency from baseline was 71.0% (p=0.0001), and 24.0% of patients achieved seizure freedom during the 8-week treatment period (p<0.0001) [99]. - The safety profile of RAP-219 was favorable, with the majority of treatment-emergent adverse events (TEAEs) being mild and a low discontinuation rate [100]. - No serious adverse events were reported during the treatment period, with 78.5% of TEAEs being mild and 21.5% moderate [103]. Formulation and Patient Adherence - Company is developing a long-acting injectable formulation of RAP-219 to improve patient adherence, with initial pharmacokinetics results expected in 2027 [27]. - A long-acting injectable (LAI) formulation of RAP-219 is under development, with initial results from a Phase 1 pharmacokinetic study anticipated in 2027 [46]. - The non-adherence rate to prescribed ASMs can be up to approximately 50%, impacting seizure control [112]. Intellectual Property and Licensing - The company owns six patent families directed to TARP8 modulators, with the first patent family expiring in 2036 and covering compositions of matter and methods of use [145]. - The company has a patent family directed to nAChR modulators that expires in 2046, which includes compositions of matter and methods of use [146]. - The company has engaged in a license agreement with Janssen Pharmaceutical NV, which includes a non-refundable upfront payment of $1.0 million and an option fee of $4.0 million for TARP8 products [153]. - Janssen is eligible to receive up to $76.0 million in development milestone payments and up to $40.0 million in sales milestone payments for the lead TARP8 development candidate [153]. - Janssen is eligible to receive royalties ranging from mid to high-single digit percentages on worldwide net sales of TARP8 products [154]. Regulatory Considerations - The FDA aims to review applications for new molecular entities within 10 months and priority review products within 6 months from the date of filing [174]. - The FDA may require a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the benefits of a product outweigh its risks, which can include special monitoring and patient registries [176]. - The FDA conducts preliminary reviews of New Drug Applications (NDAs) within 60 days to determine completeness before substantive review [174]. - The FDA will not approve an NDA unless manufacturing processes comply with current Good Manufacturing Practices (cGMP) requirements [175]. - Regulatory processes for drug approval require substantial time and financial resources, impacting overall development timelines [158]. - The FDA may impose clinical holds on trials if safety concerns arise, delaying the investigation until issues are resolved [162]. - The FDA has programs like Fast Track, Breakthrough Therapy, and Priority Review to expedite drug development for serious conditions [179]. - Fast Track designation allows for greater interaction with the FDA and rolling review of applications, but the review clock starts only after the final application section is submitted [180]. - Breakthrough Therapy designation indicates substantial improvement over existing therapies, allowing for more senior staff involvement and efficient trial design [181]. - Priority Review can shorten the FDA's review time from 10 months to 6 months for products that significantly improve safety or effectiveness [182]. - Accelerated Approval Pathway allows for earlier approval based on surrogate endpoints, requiring post-approval studies to confirm clinical benefits [183]. - The FDA mandates rigorous post-marketing compliance for products approved under accelerated pathways, including updates every 180 days [186]. Manufacturing and Supply Chain - The company relies on third-party contract manufacturing organizations (CMOs) for all manufacturing needs, with plans to enter into longer-term commercial supply agreements as product candidates advance through clinical development [134]. - The company is developing drug substance and drug product processes for commercial supply, aiming for reliable and cost-effective production [135]. - The company’s competitive factors include efficacy, safety, convenience, price, and the level of generic competition for its product candidates [138]. Market Exclusivity and Patent Regulations - Non-patent exclusivity for new chemical entities (NCE) lasts five years, preventing ANDA submissions until the exclusivity period expires [198]. - Pediatric market exclusivity can add 6 months to existing exclusivity periods if a pediatric study is completed [200]. - NDA sponsors must list all relevant patents with the FDA, which are published in the Orange Book upon approval [201]. - The ANDA or 505(b)(2) NDA cannot be approved until all listed patents have expired, unless a paragraph IV certification is provided [202]. - A patent claiming a new drug product may be eligible for a patent term extension of up to five years under the Hatch-Waxman Amendments [203]. - Innovative medicinal products approved in the EU qualify for eight years of data exclusivity and an additional two years of market exclusivity [215]. - A marketing authorization in the EU has an initial validity of five years, which can be renewed based on a re-evaluation of the risk-benefit balance [218]. - The centralized procedure for marketing authorization in the EU has a maximum evaluation timeframe of 210 days, which can be reduced to 150 days in exceptional cases [210]. - Orphan designation provides a ten-year market exclusivity period following marketing approval, with specific conditions for granting similar medicinal products [217]. - The Clinical Trials Regulation aims to streamline the approval process for clinical trials in the EU, establishing strict deadlines for application assessments [207]. - A patent term restoration cannot extend beyond a total of 14 years from the product's approval date [203]. - The mutual recognition procedure allows for the acceptance of marketing authorizations between EU Member States [212]. - Pediatric Investigation Plans (PIPs) must be approved before obtaining marketing authorization in the EU, with potential extensions for compliance [213].

Exhibit 99.1 Rapport Therapeutics Reports Fourth Quarter and Full Year 2025 Financial Results and Provides Business Update BOSTON and SAN DIEGO, March 10, 2026 -- Rapport Therapeutics, Inc. (Nasdaq: RAPP) ("Rapport" or the "Company"), a clinical-stage biotechnology company dedicated to the discovery and development of small molecule precision medicines for patients with neurological and psychiatric disorders, today reported financial results for the quarter and full year ended December 31, 2025, and provide ...

Core Viewpoint - Rapport Therapeutics reported strong progress in its precision neuroscience pipeline, particularly with the lead program RAP-219 for epilepsy, which is expected to have a significant market opportunity if approved [2][6]. Financial Results - The company reported a net loss of $33.8 million for Q4 2025, compared to a loss of $20.0 million in Q4 2024. For the full year 2025, the net loss was $111.5 million, up from $78.3 million in 2024 [12][18]. - Research and Development (R&D) expenses for Q4 2025 were $30.3 million, an increase from $17.2 million in Q4 2024. For the full year, R&D expenses totaled $94.8 million, compared to $60.9 million in 2024 [12][13]. - General and Administrative (G&A) expenses for Q4 2025 were $8.3 million, up from $6.3 million in Q4 2024. For the full year, G&A expenses were $30.3 million, compared to $22.1 million in 2024 [12][13]. Pipeline Developments - RAP-219 demonstrated robust activity in patients with focal onset seizures (FOS) during the Phase 2a trial, with a median reduction in clinical seizure frequency of 77.8% and 72% of patients achieving a ≥50% reduction in seizures [6][5]. - The company plans to initiate a Phase 3 program for RAP-219 in FOS in Q2 2026, accelerated from previous guidance [7][6]. - Rapport is expanding its epilepsy portfolio to include primary generalized tonic-clonic seizures (PGTCS) based on the Phase 2a data from FOS [11][5]. Strategic Collaborations - In March 2026, the company entered a strategic collaboration with Tenacia Biotechnology to develop and commercialize RAP-219 in Greater China, which includes an upfront payment of $20 million and potential milestone payments totaling approximately $308 million [9][5]. Cash Position - As of December 31, 2025, the company had $490.5 million in cash, cash equivalents, and short-term investments, which is expected to fund operations into the second half of 2029 [18][12].

此次合作依托Tenacia在中枢神经系统（CNS）药物开发与商业化方面的专长，加速RAP-219在美国及全球的开发进程 Tenacia获得大中华区RAP-219开发和商业化的独家权利，针对病症包括局灶性发作癫痫和双相躁狂等适应症 Rapport将获得2000万美元的现金预付款，最高可达3.08亿美元的潜在开发与商业化里程碑款项及其他付款，以及个位数中段到十几中段的分级特许权使用费 波士顿和上海, March 10, 2026 (GLOBE NEWSWIRE) -- 致力于为神经和精神疾病患者发现并开发小分子精准药物的临床阶段生物技术公司Rapport Therapeutics, Inc.（Nasdaq：RAPP）（以下简称“Rapport”）与致力于为医疗需求未得到充分满足的神经疾病患者开发创新疗法的商业化阶段生物制药公司Tenacia Biotechnology (Hong Kong) Co., Ltd（以下简称“Tenacia”）今日宣布达成合作，授予Tenacia在大中华区（包括中国大陆、香港、澳门和台湾）开发及商业化RAP-219的独家权利。 RAP-219是一种潜在的首创TARPγ8特异性AMPA受 ...

Core Insights - The partnership between Rapport Therapeutics and Tenacia Biotechnology aims to leverage Tenacia's expertise in CNS drug development to accelerate the global development of RAP-219, a potential first-in-class therapy for neurological disorders [1][4] Financial Terms - Rapport will receive an upfront cash payment of $20 million, with potential additional payments of up to $308 million in development and commercialization milestones, along with tiered royalties on net sales in Greater China [3][4] Product Development - RAP-219 is being developed for multiple indications, including focal onset seizures and bipolar mania, and has shown promising results in a Phase 2a trial, demonstrating significant reductions in seizure episodes [2][6] - Two global registrational trials for RAP-219 will be conducted, with a Phase 3 program expected to start in Q2 2026, expanding its clinical trial sites in China under Tenacia's leadership [2][3] Company Profiles - Rapport Therapeutics focuses on developing small molecule precision medicines for neurological and psychiatric disorders, with a strong emphasis on epilepsy and bipolar disorder [7] - Tenacia Biotechnology, founded in 2022, aims to develop innovative therapeutics for underserved neurological disorders and is backed by Bain Capital, enhancing its capabilities in drug development [8]

Rapport Therapeutics FY Conference Summary Company Overview - **Company**: Rapport Therapeutics (NasdaqGM:RAPP) - **Industry**: Biotechnology, specifically focusing on neuroscience and epilepsy treatments Key Highlights from 2025 and Early 2026 - 2025 was a transformational year for Rapport, showcasing confirmatory data for their approach in precision neuroscience, particularly with their lead program RAP-219 targeting focal-onset seizures [3][4] - Proof-of-concept data released in September 2025 demonstrated a **72% reduction** in a novel biomarker and a **78% reduction** in clinical seizures in a refractory patient population [4][5] - A **24% seizure freedom rate** was also reported, allowing progression into registrational studies [5] Upcoming Clinical Trials - Phase 3 program for RAP-219 will be initiated in Q2 2026, accelerated from Q3 due to positive FDA interactions [5] - Two pivotal trials will be conducted in parallel, focusing on refractory focal-onset seizure patients, with three dose levels: low (0.25 mg), mid (0.75 mg), and high (1.25 mg) [6][7] Patient Population Insights - The proof-of-concept study enrolled patients with an RNS device, showing demographic similarities to those in traditional studies, but with a higher refractory rate [8][9] - 70% of enrolled patients were on 3-4 medications, indicating a highly refractory population [9] Efficacy and Safety Expectations - A clinically meaningful placebo-adjusted seizure reduction target is set at **30%-35%**, with a non-placebo adjusted target of **50%-55%** [10] - Emphasis on tolerability and ease of administration is crucial for market adoption, with a preference for once-daily dosing and minimal drug-drug interactions [11][12] Tolerability Profile - The phase 2 study reported only mild to moderate adverse events (AEs), with no severe AEs observed [14] - Anxiety was noted in some patients, but it was attributed to preexisting conditions rather than the drug itself [15][16] Market Opportunity - The market opportunity for RAP-219 in focal-onset seizures is estimated at **$2.5 billion**, based on a refractory population of 30%-40% of 1.8 million patients [18] - A long-acting injectable formulation is also in development, which could further enhance market potential [19] Long-Acting Injectable Insights - KOLs believe a long-acting injectable would be transformational for patients, addressing concerns about missed doses leading to breakthrough seizures [20][21] - The development of RAP-219 as a long-acting injectable is supported by its extended half-life and low solubility, making it suitable for this formulation [22][23] Enrollment and Trial Dynamics - Current trends show varying enrollment timelines for pivotal studies, with some taking 2-4 years [25] - Rapport aims to leverage excitement in the community and the completion of other ongoing trials to facilitate patient recruitment [26][27] Bipolar Mania Program - RAP-219 is also being explored for bipolar mania, with a focus on its potential to reduce excessive glutamate associated with the condition [28][29] - The primary endpoint for the bipolar mania trial is the Young Mania Rating Scale (YMRS), with a meaningful effect defined as a **4-point placebo-adjusted change** [35] Pain Program Focus - The company has shifted focus to a nicotinic acetylcholine receptor program for pain, which has shown promise in preclinical models [37][38] Financial Outlook - Rapport is funded into the second half of 2029, allowing for the completion of the phase 3 trial in focal-onset seizures and the phase 2 trial in bipolar mania [39] Strategic Positioning - The company is positioned to execute its programs independently, with no immediate plans for partnerships, although it remains open to opportunities that do not compromise its initiatives [42][43][44]