Core Insights - Rapport Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing small molecule precision medicines for neurological and psychiatric disorders [4] - The company will present data on its investigational drug RAP-219 at the 2025 American Academy of Neurology Annual Meeting, highlighting its potential in treating refractory focal epilepsy [1][2] Group 1: Company Overview - Rapport Therapeutics specializes in discovering and developing precision medicines targeting neurological and psychiatric disorders, leveraging its RAP technology platform [4] - The company's lead product, RAP-219, is designed to selectively target TARPγ8, a receptor associated protein, to achieve neuroanatomical specificity [3][4] - The company is also exploring RAP-219 for other conditions, including bipolar disorder and peripheral neuropathic pain, indicating a broad therapeutic potential [3][4] Group 2: Research and Development - RAP-219 is currently in Phase 2 development for refractory focal epilepsy, showcasing its role as an AMPA receptor negative allosteric modulator [2][3] - The upcoming presentations will include findings on the optimal cut point for seizure frequency reduction and the antiseizure effects of RAP-219 in preclinical models [6] - Data from the presentations suggest a 30% reduction in long episode frequency correlates with a clinically meaningful reduction in seizures, and RAP-219 demonstrated potent, dose-dependent antiseizure effects in preclinical models [6]

Drug Development and Clinical Trials - RAP-219 is a precision small molecule designed to selectively target TARP8, achieving neuroanatomical specificity and potentially transforming treatment for focal epilepsy, bipolar disorder, and peripheral neuropathic pain[20]. - Four Phase 1 trials of RAP-219 have been completed, demonstrating well-tolerated results and achieving target receptor occupancy associated with maximal seizure protection in preclinical models[21]. - A Phase 2a proof-of-concept trial for RAP-219 in refractory focal epilepsy is ongoing, with topline results expected in Q3 2025[22]. - The Phase 2a trial is expected to report topline results in Q3 2025, with potential for RAP-219 to provide translatable proof-of-concept for future focal epilepsy trials[98]. - The Phase 2a proof-of-concept trial of RAP-219 aims to enroll approximately 20 participants with an RNS system, with a primary endpoint of reducing long episode (LE) frequency by at least 30% compared to baseline[92][93]. - A collaboration with NeuroPace was established to leverage RNS system data for tracking patient responses in the Phase 2a trial, enhancing patient recruitment efficiency[94]. - Ongoing studies are assessing longer-term dosing and reproductive toxicity, with initial findings indicating a low risk of convulsion[81]. - Clinical trials are conducted in three phases, with Phase 1 focusing on safety and dosage, Phase 2 on efficacy, and Phase 3 on generating data for approval[172]. Market Potential and Unmet Needs - The total branded market for epilepsy was approximately $2.8 billion in 2022 and is projected to grow to approximately $3.6 billion by 2028[28]. - Approximately 30 to 40 percent of epilepsy patients experience refractory epilepsy despite taking two or more antiseizure medications, highlighting the need for new therapies[29]. - Epilepsy affects approximately 50 million people globally, with 3.0 million adults in the United States, and the annual direct costs in the U.S. are estimated at $28 billion[50]. - Focal epilepsy accounts for 60% of all epilepsies, with the unpredictable nature of seizures significantly impacting patient quality of life[51]. - The global bipolar disorder market was approximately $1.4 billion in 2022, expected to grow to over $4 billion by 2028, indicating significant market potential for RAP-219 in this indication[106]. - Peripheral neuropathic pain is estimated to affect up to 17% of the global population, with a market size of approximately $6.6 billion in 2021, forecasted to grow at over 4% annually[108]. - Significant unmet need in the treatment of peripheral neuropathic pain, with most available treatments having only moderate efficacy and associated side effects[110]. Drug Mechanism and Pharmacology - RAP-219 aims to improve tolerability and adherence by precisely modulating only diseased brain regions, potentially offering a better therapeutic index compared to existing antiseizure medications[32]. - RAP-219 is designed as a highly potent and selective NAM of TARP8-AMPAR, demonstrating antiseizure activity in preclinical models without motoric impairment or sedation[8]. - RAP-219's pharmacology studies indicate it may treat bipolar disorder and peripheral neuropathic pain, in addition to focal epilepsy[49]. - Preclinical studies support RAP-219's pharmacodynamic properties, with earlier generation TARP8 NAMs showing similar effects[62]. - The tolerability profile of RAP-219 is expected to be differentiated from perampanel, which has a high incidence of side effects such as dizziness and somnolence[61]. - The differentiated mechanism of action of RAP-219 may provide superior clinical activity compared to currently approved antiseizure medications, potentially reducing intolerable adverse effects[101]. Safety and Tolerability - In Phase 1 trials, RAP-219 was generally well tolerated with only 3% of participants discontinuing due to treatment emergent adverse events[83]. - No adverse effects were observed in a 28-day GLP toxicology study in rats, supporting the drug's tolerability[80]. - Among 48 participants exposed to RAP-219, the most common treatment-emergent adverse events (TEAEs) were headache (n=5), sinus tachycardia (n=4), and brain fog, insomnia, bowel movement irregularity, dry mouth, and medical device site reaction (n=3 each)[88]. Competitive Landscape - RAP-219 faces competition from existing therapies for focal epilepsy, including XCOPRI and FYCOMPA, as well as various therapies in clinical development[135]. - In bipolar disorder, RAP-219 competes with mood stabilizers and antidepressants, with additional competition from BHV-7000 in clinical development[136]. - For peripheral neuropathic pain, competition includes existing therapies such as duloxetine and gabapentin, along with clinical candidates like VX-548 and BHV-2100[137]. Intellectual Property and Licensing - The company holds six patent families related to TARP8 modulators, with expiration dates ranging from 2036 to 2045, and multiple pending applications[141]. - The company has a license agreement with Janssen Pharmaceutical NV, which includes potential milestone payments of up to $76 million for TARP8 products[150]. - The company will pay Janssen a total of $5 million in upfront and option fees related to the TARP8 license agreement[150]. - The company emphasizes the importance of maintaining and defending its intellectual property rights to ensure commercial success[139]. Regulatory Considerations - The FDA requires completion of nonclinical tests, submission of an IND, and approval by an IRB before human clinical trials can begin[160]. - An IND becomes effective 30 days after submission unless the FDA raises concerns, which can lead to a clinical hold[162]. - The FDA aims to review NDAs for new molecular entities within 10 months, and priority review applications within 6 months[181]. - The FDA may grant accelerated approval for products that provide meaningful therapeutic advantages based on surrogate endpoints[182]. - The FDA may impose restrictions on marketing and distribution based on post-market studies, which can significantly affect market potential and profitability[188].

Financial Performance - Net loss for Q4 2024 was $20.0 million, compared to $13.5 million in Q4 2023; full year net loss was $78.3 million, up from $34.8 million in 2023[12] - Net loss for the year ended December 31, 2024, was $78,307,000, up from a net loss of $34,786,000 in 2023, reflecting a 125% increase in losses[25] - Total operating expenses for the year ended December 31, 2024, were $83,055,000, compared to $36,179,000 in 2023, marking an increase of 130%[25] - Net cash used in operating activities for the year ended December 31, 2024, was $64,828,000, compared to $27,181,000 in 2023, an increase of 139%[27] Research and Development - Research and Development (R&D) expenses for Q4 2024 were $17.2 million, an increase from $11.8 million in Q4 2023; full year R&D expenses totaled $60.9 million, compared to $28.0 million in 2023[12] - Research and development expenses rose to $60,935,000 for the year ended December 31, 2024, compared to $27,999,000 in 2023, an increase of 118%[25] - The company expects to initiate a Phase 2a trial in bipolar mania in Q3 2025, with topline results anticipated in the first half of 2027[4] - Topline results for the Phase 2a trial in refractory focal epilepsy are expected in Q3 2025, narrowing the timeline from prior guidance[7] - The company plans to finalize its trial plans for diabetic peripheral neuropathic pain after receiving a clinical hold from the FDA[9] - The recently released PET and MAD-2 trial results support RAP-219's potential for CNS disorders, demonstrating neuroanatomical specificity and favorable tolerability[4] Cash and Investments - The company ended Q4 2024 with $305.3 million in cash, cash equivalents, and short-term investments, down from $320.7 million as of September 30, 2024[13] - Cash and cash equivalents decreased to $56,805,000 in 2024 from $70,169,000 in 2023, a decline of 19%[22] - Cash runway is expected to fund operations through the end of 2026[13] - Net cash provided by financing activities for the year ended December 31, 2024, was $221,625,000, compared to $145,136,000 in 2023, an increase of 53%[27] Administrative Expenses - General and Administrative (G&A) expenses for Q4 2024 were $6.3 million, up from $3.0 million in Q4 2023; full year G&A expenses were $22.1 million, compared to $8.2 million in 2023[12] Assets and Liabilities - Total assets increased to $314,933,000 in 2024 from $155,423,000 in 2023, representing a growth of 102%[22] - Total liabilities decreased to $9,506,000 in 2024 from $14,479,000 in 2023, a reduction of 34%[22] Personnel Changes - The company appointed Dr. Jeffrey Sevigny as Chief Medical Officer, bringing over 15 years of experience in translational and clinical drug development[10] Shareholder Information - The weighted-average common shares outstanding increased to 20,738,338 in 2024 from 1,505,774 in 2023, a growth of 1,276%[25] - Interest income for the year ended December 31, 2024, was $12,138,000, up from $2,527,000 in 2023, an increase of 381%[25]

Core Viewpoint - Rapport Therapeutics is advancing its lead program RAP-219, targeting neurological and psychiatric disorders, with significant clinical milestones expected in the near future [2][4]. Business Highlights - The Phase 2a trial of RAP-219 for refractory focal epilepsy is progressing well, with topline results anticipated in Q3 2025 [2][4]. - A Phase 2a trial for bipolar mania is expected to start in Q3 2025, with results projected in the first half of 2027 [6]. - The company appointed Dr. Jeffrey Sevigny as Chief Medical Officer, bringing extensive experience in drug development [8]. - As of December 31, 2024, the company reported $305.3 million in cash and equivalents, sufficient to fund operations through the end of 2026 [4][12]. Clinical Development - Recent PET and MAD-2 trial results support RAP-219's potential for treating CNS disorders, demonstrating neuroanatomical specificity and favorable tolerability [5][10]. - The company is finalizing plans for a Phase 2a trial in diabetic peripheral neuropathic pain after receiving feedback from the FDA [7]. Financial Results - For Q4 2024, the net loss was $20.0 million, compared to $13.5 million in the same period of the previous year [11]. - Research and Development expenses increased to $17.2 million in Q4 2024 from $11.8 million in Q4 2023, reflecting higher operational costs [11]. - General and Administrative expenses rose to $6.3 million in Q4 2024 from $3.0 million in Q4 2023, driven by business growth and public company requirements [11]. Cash Position - The company ended Q4 2024 with $305.3 million in cash, down from $320.7 million at the end of Q3 2024, primarily due to operating cash outflows [11][12].

Company Overview - Rapport Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing small molecule precision medicines for central nervous system (CNS) disorders [6] - The company utilizes a unique RAP technology platform that targets receptor associated proteins (RAPs) in the brain, aiming to create precision small molecule candidates that address limitations in conventional neurology drug discovery [6] Leadership Appointment - Dr. Jeffrey Sevigny has been appointed as the chief medical officer (CMO) of Rapport Therapeutics, bringing over 15 years of experience in translational and clinical drug development [1][2] - Dr. Sevigny previously served as CMO at Prevail Therapeutics and held senior roles at Eli Lilly, where he contributed to significant corporate successes including financing rounds, an IPO, and an acquisition [2][4] Clinical Strategy and Pipeline - As CMO, Dr. Sevigny will oversee the clinical strategy and advancement of Rapport's pipeline, particularly the RAP-219 program, which is currently in clinical trials for conditions such as focal epilepsy, diabetic peripheral neuropathic pain, and bipolar mania [3][6] - The RAP-219 program is noted for its compelling Phase 1 data and aims to achieve neuroanatomical specificity by selectively targeting RAPs expressed in specific brain regions [5][6] Company Vision and Goals - The CEO of Rapport, Abraham N. Ceesay, expressed confidence in Dr. Sevigny's ability to lead the clinical development team and emphasized the importance of collaboration with regulatory authorities and patient advocacy organizations [4] - Dr. Sevigny highlighted the company's strong scientific foundation and the potential of its clinical candidates to provide transformative treatment options for patients with neurological disorders [5]

Company Overview - Rapport Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing small molecule precision medicines for central nervous system (CNS) disorders [3] - The company utilizes a unique RAP technology platform based on pioneering discoveries related to receptor associated proteins (RAPs) in the brain, allowing for a differentiated approach in drug discovery [3] - The precision neuroscience pipeline includes the lead clinical program RAP-219, which targets specific RAPs in discrete brain regions and is currently in trials for focal epilepsy, diabetic peripheral neuropathic pain, and bipolar mania [3] Upcoming Events - Management will present at the TD Cowen 45 Annual Health Care Conference in Boston on March 4, 2025, from 3:10 to 3:40 PM EST [1] - The company will also participate in the Stifel 2025 Virtual CNS Forum on March 19, 2025, from 10:30 to 10:55 AM EST [2] - Live and archived webcasts of these presentations will be available on the company's website under the "Investors" section [2]

Core Insights - Rapport Therapeutics, Inc. announced positive results from its PET and MAD-2 trials for RAP-219, indicating its potential as a treatment for focal epilepsy and other CNS disorders [1][2][3] Trial Results - In the PET trial, RAP-219 achieved target receptor occupancy (RO) associated with maximal efficacy within five days of dosing, confirming the neuroanatomical expression of TARPγ8 [1][10] - The MAD-2 trial demonstrated that RAP-219 was generally well tolerated, with no serious adverse events and favorable tolerability across various dosing regimens [2][11] - The ongoing Phase 2a trial of RAP-219 in focal epilepsy is on track, with topline data expected in mid-2025 [1][7] Drug Profile - RAP-219 is designed as a selective AMPA receptor negative allosteric modulator targeting TARPγ8, which is enriched in the hippocampus and cerebral cortex, potentially leading to improved tolerability compared to traditional treatments [8][9] - The drug has a long half-life of 8-14 days and minimal drug-drug interactions, making it suitable for patients on multiple medications [8] Company Overview - Rapport Therapeutics focuses on developing small molecule precision medicines for CNS disorders, leveraging its RAP technology platform to create differentiated product candidates [9] - The company is advancing RAP-219 for multiple indications, including focal epilepsy, diabetic peripheral neuropathic pain, and bipolar mania [9]

Core Viewpoint - Rapport Therapeutics, Inc. announced positive results from its PET and MAD-2 trials for RAP-219, indicating its potential as a differentiated treatment for focal epilepsy with a favorable tolerability profile and broad therapeutic index [1][2][3]. Group 1: Trial Results - In the PET trial, RAP-219 achieved target receptor occupancy (RO) associated with maximal efficacy within five days of dosing, confirming the neuroanatomical expression of TARPγ8 [1][10]. - The MAD-2 trial demonstrated that RAP-219 was generally well tolerated, with no serious adverse events and a favorable tolerability profile consistent with prior Phase 1 trials [2][11]. - Data from both trials support the ongoing Phase 2a trial in focal epilepsy, with topline results expected in mid-2025 [1][7]. Group 2: Drug Profile - RAP-219 is designed as a clinical-stage AMPA receptor negative allosteric modulator, selectively targeting TARPγ8 to achieve neuroanatomical specificity, which may enhance tolerability compared to traditional treatments [8][12]. - The drug has a long half-life of 8-14 days and minimal drug-drug interactions, making it suitable for patients on multiple medications [8]. - The selective targeting of TARPγ8 may provide a pipeline-in-a-product opportunity for various neurological disorders, including focal epilepsy, diabetic peripheral neuropathic pain, and bipolar mania [8][12]. Group 3: Company Overview - Rapport Therapeutics is a clinical-stage biotechnology company focused on developing small molecule precision medicines for central nervous system disorders [9]. - The company utilizes its RAP technology platform to generate differentiated product candidates, aiming to improve therapeutic outcomes for patients suffering from CNS disorders [9].

In the PET trial, RAP-219 achieved and exceeded target receptor occupancy, increasing support for the dosing regimen utilized in the ongoing Phase 2a trial in focal epilepsy; restricted neuroanatomical expression of TARP8 was confirmed In the MAD-2 trial, RAP-219 was observed to be generally well tolerated with faster titration and higher exposures than in the initial MAD trial Data underscore the potential broad therapeutic index of RAP-219 and dosing flexibility Ongoing Phase 2a trial of RAP-219 in foca ...

Core Insights - Rapport Therapeutics announced positive results from the PET and MAD-2 trials for RAP-219, indicating its potential for treating focal epilepsy and demonstrating a favorable tolerability profile [1][2][3] Group 1: Trial Results - In the PET trial, RAP-219 achieved target receptor occupancy (RO) associated with maximal efficacy within five days of dosing, confirming the neuroanatomical expression of TARP8 [1][12] - The MAD-2 trial showed RAP-219 was generally well tolerated, with no serious adverse events and a favorable tolerability profile across various dosing regimens [2][13] - Both trials underscored the potential broad therapeutic index of RAP-219 and its dosing flexibility, with topline data from the ongoing Phase 2a trial expected in mid-2025 [1][8] Group 2: Drug Profile - RAP-219 is designed as a selective AMPA receptor negative allosteric modulator targeting TARP8, which is enriched in the hippocampus and cerebral cortex, potentially leading to improved tolerability compared to traditional treatments [9][10] - The drug has a long half-life of 8-14 days and minimal drug-drug interactions, making it suitable for patients on multiple medications [9] - The company is pursuing RAP-219 for various conditions, including focal epilepsy, diabetic peripheral neuropathic pain, and bipolar mania, indicating a broad application potential [9][10] Group 3: Company Developments - Rapport Therapeutics is a clinical-stage biotechnology company focused on developing small molecule precision medicines for CNS disorders, leveraging its RAP technology platform [10] - The company has conducted four Phase 1 trials with 100 healthy volunteers, demonstrating the safety and tolerability of RAP-219 [2][10] - A leadership change was announced with the resignation of the chief medical officer, although the company expressed confidence that this would not disrupt ongoing clinical programs [3]