Core Insights - Rapport Therapeutics, Inc. is hosting its inaugural Investor and Analyst Day on June 2, 2025, in New York City, which will also be webcast live [1][3] Company Overview - Rapport Therapeutics is a clinical-stage biotechnology company focused on developing small molecule precision medicines for neurological and psychiatric disorders [4] - The company utilizes a unique RAP technology platform based on discoveries related to receptor associated proteins (RAPs) in the brain, aiming to create precision small molecule candidates [4] - The lead investigational drug, RAP-219, targets specific regions of the brain and is being developed for refractory focal epilepsy, bipolar mania, and diabetic peripheral neuropathic pain [4] Event Details - The Investor and Analyst Day will feature a review of the company's clinical programs, particularly the RAP-219 Phase 2a trial in refractory focal epilepsy [2] - A fireside chat with Dr. Jacqueline A. French, a prominent figure in epilepsy research, will be part of the event [2] - The event is scheduled for June 2, 2025, from 3:00 to 5:00 p.m. Eastern Time at Nasdaq MarketSite, New York City [3]

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.

Financial Performance - The company has not generated any revenue from product sales since its inception in February 2022, incurring significant operating losses and negative cash flows [159]. - As of March 31, 2025, the company reported net losses of $24.1 million and an accumulated deficit of $147.8 million [160]. - The net loss for the three months ended March 31, 2025, was $24.1 million, compared to a net loss of $22.7 million in 2024, indicating an increase in loss of $1.4 million [186]. - The company expects to incur significant operating losses and expenses as it advances clinical development, projecting a $2.6 million increase in workforce expenses due to headcount growth [192]. Funding and Capital - The company completed its initial public offering in June 2024, raising net proceeds of $157.6 million from the sale of 9,200,000 shares of common stock [159]. - The company has raised aggregate gross proceeds of $424.4 million from various financings as of March 31, 2025 [159]. - The company raised aggregate gross proceeds of $424.4 million from the issuance of convertible promissory notes and the sale of convertible preferred stock and common stock [193]. - The company anticipates needing to raise substantial additional capital in the future to support ongoing activities and product development [201]. - The company expects its existing cash resources to be sufficient to fund operations through at least 12 months from the issuance of the financial statements [200]. Research and Development - The company is conducting a Phase 2a proof-of-concept trial for RAP-219 in patients with refractory focal epilepsy, with topline results expected in Q3 2025 [157]. - The FDA placed a clinical hold on the IND for a Phase 2a trial of RAP-219 for diabetic peripheral neuropathic pain, requesting additional information [157]. - The company has two advanced discovery-stage nicotinic acetylcholine receptor programs targeting chronic pain and hearing disorders [158]. - Research and development expenses increased to $19.6 million for the three months ended March 31, 2025, compared to $12.5 million for the same period in 2024, representing a $7.1 million increase [186]. - The increase in research and development expenses was primarily driven by a $4.1 million rise in costs associated with the RAP-219 program, including clinical trial costs for multiple trials [187]. - The company anticipates substantial increases in research and development expenses as it advances RAP-219 through clinical development and regulatory approval [176]. Operating Expenses - Total operating expenses for the three months ended March 31, 2025, were $27.1 million, compared to $17.1 million in 2024, resulting in a $10.0 million increase [186]. - General and administrative expenses rose to $7.5 million for the three months ended March 31, 2025, up from $4.6 million in 2024, reflecting a $2.9 million increase [190]. - The company expects general and administrative expenses to continue increasing to support product candidate development and research activities [180]. Cash Flow and Investments - As of March 31, 2025, the company had cash and cash equivalents of $285.4 million, excluding restricted cash [193]. - For the three months ended March 31, 2025, the company incurred a net loss of $24.1 million, with cash used in operating activities amounting to $20.2 million [195]. - Net cash provided by investing activities for the three months ended March 31, 2025, was $21.0 million, primarily from maturities of short-term investments [197]. - During the three months ended March 31, 2024, the company had a net cash provided by financing activities of $63.7 million, primarily from the issuance of Series B convertible preferred stock [199]. Agreements and Collaborations - The company has entered into a license agreement with Janssen Pharmaceutical NV, which includes potential milestone payments totaling up to $141 million for TARPg8 products [167][168]. - The company made a non-refundable payment of $1.0 million to Janssen Pharmaceutical NV as part of a licensing agreement, with potential milestone payments totaling up to $76.0 million for development [205]. - The NeuroPace Agreement allows the company to utilize data from RNS systems in clinical trials, with an exclusivity provision preventing NeuroPace from providing similar services to competitors [170][171]. Other Financial Information - The company has recorded a full valuation allowance against its net deferred tax assets, with federal net operating loss carryforwards of approximately $13.7 million as of December 31, 2024 [185]. - The change in fair value of preferred stock tranche right liabilities was settled in March 2024, resulting in no further recognition of changes in fair value in the financial statements [183]. - Future minimum operating lease payments under non-cancelable leases total $9.3 million, with a weighted average remaining lease term of 4.4 years [203][204].

Financial Performance - Net loss for Q1 2025 was $24.1 million, compared to $22.7 million for the same period last year, reflecting an increase in operational costs [12]. - Net loss for the three months ended March 31, 2025, was $24,063,000 compared to a net loss of $22,669,000 for the same period in 2024, reflecting an increase in loss of about 6.1% [27]. - Total operating expenses rose from $17,094,000 to $27,108,000, an increase of approximately 58.8% [27]. - Net cash used in operating activities increased from $17,615,000 to $20,237,000, a rise of approximately 14.8% [29]. - Total liabilities increased from $9,506,000 to $16,217,000, an increase of approximately 70.5% [24]. - Total stockholders' equity decreased from $305,427,000 to $285,836,000, a decline of about 6.4% [24]. Research and Development - Research and Development (R&D) expenses rose to $19.6 million in Q1 2025, up from $12.5 million in the prior year, driven by clinical development costs [17]. - Research and development expenses increased significantly from $12,504,000 to $19,572,000, representing a rise of about 56.5% [27]. - Enrollment in the Phase 2a trial for RAP-219 in refractory focal epilepsy is progressing as planned, with topline results expected in Q3 2025 [4]. - The Phase 2a trial for RAP-219 in bipolar mania is set to commence in Q3 2025, with topline results anticipated in the first half of 2027 [4]. - Favorable tolerability was reported across four Phase 1 trials, with no serious adverse events and only 3% of participants discontinuing due to treatment emergent adverse events [7]. - The optimal cut point for a clinically meaningful reduction in seizure frequency was identified as a 30% reduction in long episode frequency [8]. Cash and Investments - The company ended Q1 2025 with $285.4 million in cash, cash equivalents, and short-term investments, down from $305.3 million at the end of 2024 [17]. - The company expects its cash position to fund operations through the end of 2026 [17]. - Net cash provided by investing activities was $21,031,000, contrasting with a net cash used of $41,926,000 in the previous year [29]. Corporate Events - The company plans to host its inaugural Investor and Analyst Day on June 2, 2025, featuring presentations from management and key opinion leaders [4]. Shareholder Information - The weighted-average common shares outstanding increased from 2,046,889 to 35,266,577, indicating a significant dilution of shares [27]. - General and Administrative (G&A) expenses increased to $7.5 million in Q1 2025, compared to $4.6 million in the same period last year, due to business growth and public company operational costs [17].

Core Insights - Rapport Therapeutics is focused on developing small molecule precision medicines for neurological and psychiatric disorders, with significant progress expected in 2025 [1][14] Business Highlights - The Phase 2a trial for RAP-219 in refractory focal epilepsy is on track, with topline results anticipated in Q3 2025 [4] - The Phase 2a trial for RAP-219 in bipolar mania is set to begin in Q3 2025, with topline results expected in the first half of 2027 [6] - The company ended Q1 2025 with $285.4 million in cash and equivalents, sufficient to fund operations through the end of 2026 [4][17] Clinical Development - Recent PET trial results validate the neuroanatomical specificity of TARPγ8 and the tolerability profile of RAP-219, enhancing confidence in its potential [2][5] - RAP-219 demonstrated receptor occupancy levels associated with maximal seizure protection within five days of dosing in human trials [5] - Favorable tolerability was reported across four Phase 1 trials, with no serious adverse events noted [5] Financial Results - The net loss for Q1 2025 was $24.1 million, compared to $22.7 million in the same period last year [11] - Research and Development expenses increased to $19.6 million in Q1 2025 from $12.5 million in the prior year, driven by clinical development costs [11] - General and Administrative expenses rose to $7.5 million in Q1 2025 from $4.6 million in the previous year, reflecting business growth and public company operational costs [11] Future Plans - The company plans to host its inaugural Investor and Analyst Day on June 2, 2025, featuring key presentations [11] - An update on the timeline for the Phase 2a trial in Diabetic Peripheral Neuropathic Pain (DPNP) is expected in 2025, following a clinical hold by the FDA [7]

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]

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].