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RAP-219 Phase 2a Trial in Drug-resistant Focal Onset Seizures Topline Results Conference Call Presentation September 8, 2025
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Disclaimer This presentation contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, but are not limited to, express or implied statements regarding: the clinical development of RAP-219 for the treatment of focal onset seizures, bipolar mania and diabetic peripheral neuropathic pain, including the initiation, timing, progress and results of the Company's Phase 3 clinical trials in focal onset seizures, and a Phase 2a clinical trial of RAP-219 in bipolar mania, as well as other planned clinical trials; expectations for the activity, tolerability, and commercial potential of RAP-219; the future release of data from the ongoing 8-week follow-up period of the Phase 2a trial for RAP-219; expectations for a long-acting injectable (LAI) formulation of RAP-219 and the potential of a LAI to improve patient adherence; the Company's expectations for upcoming regulatory interactions; the potential of Rapport's RAP technology platform; the advancement of the Company's discovery programs; and expectations for Rapport's uses of capital, expenses and financial results, including its cash runway through the end of 2026. Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect Rapport’s business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to the Company’s research and development activities; Rapport’s ability to execute on its strategy including obtaining the requisite regulatory approvals on the expected timeline, if at all; uncertainties relating to preclinical and clinical development activities; the Company’s dependence on third parties to conduct clinical trials, manufacture its product candidates and develop and commercialize its product candidates, if approved; Rapport’s ability to attract, integrate and retain key personnel; risks related to the Company’s financial condition and need for substantial additional funds in order to complete development activities and commercialize a product candidate, if approved; risks related to regulatory developments and approval processes of the U.S. Food and Drug Administration and comparable foreign regulatory authorities; risks related to establishing and maintaining Rapport’s intellectual property protections; and risks related to the competitive landscape for Rapport’s product candidates; as well as other risks described in “Risk Factors,” in the Company’s Annual Report on Form 10-K and most recent Quarterly Report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in Rapport’s subsequent filings with the Securities and Exchange Commission. Any forward-looking statements represent Rapport’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Rapport expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. 2
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Agenda 01 Overview Abe Ceesay, Chief Executive Officer 02 RAP-219 in Drug-resistant Focal Onset Seizures Topline Phase 2a Data Jeff Sevigny, M.D., Chief Medical Officer 03 Closing Remarks Abe Ceesay 04 Questions and Answers Abe Ceesay | Jeff Sevigny | Troy Ignelzi, Chief Financial Officer 3
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Agenda 01 Overview Abe Ceesay, Chief Executive Officer 02 RAP-219 in Drug-resistant Focal Onset Seizures Topline Phase 2a Data Jeff Sevigny, M.D., Chief Medical Officer 03 Closing Remarks Abe Ceesay 04 Questions and Answers Abe Ceesay | Jeff Sevigny | Troy Ignelzi, Chief Financial Officer 4
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TARPγ8 Clinical PET 5 Foundational science and supportive research established our early confidence in RAP-219 High expression in the neocortex and mesial temporal lobe, where nearly all seizures originate Relatively low expression in hindbrain Corneal Kindling Responders and Rotarod Failures in Mice Robust, dose-dependent seizure protection in gold-standard preclinical model Clear confirmation that TARPγ8 is broadly expressed in brain regions associated with the initiation and propagation of FOS
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6 Unmet need in epilepsy highlights limitations of current antiseizure medications a Drug-resistant patients are those who continue to experience recurring seizures despite taking two or more ASMs; b Source: Epilepsy Foundation. ASM – antiseizure medication Limitations of antiseizure medications (ASMs) 3.0M U.S. Epilepsy Patients (ages 18+) 60% Focal Seizures 1.8M Focal Onset Seizure Patients 30-40% Drug-resistanta Limited Efficacy: Despite over 30 FDA approved ASMs, 30- 40% of patients are still drug-resistanta Tolerability Issues: Burdensome side-effects, such as sedation, ataxia, and cognitive problems Potential for Serious Adverse Events: Such as severe cutaneous reactions, serious hematological disorders, and hepatic failure Risk of Breakthrough Seizures: Missing doses of medicines with short half-lives create potential for breakthrough seizuresb Complicated Administration: Long titration, drug-drug interactions, overlapping mechanisms, and lab monitoring
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7 Emerging best-in-class profile for RAP-219 in focal onset seizures, with multi-billion dollar commercial opportunity, if approved Efficacy Data Phase 2a results demonstrated statistically significant reductions in long episodes and clinical seizures Tolerability Data RAP-219 was generally well-tolerated in Phase 2a Ease of Use Once daily dosing, low risk of drug-drug interactions, rational polypharmacy potential, and long half- life Long-acting Injectable Advancing first ever LAI for epilepsy patients, providing IP extension leading to potential commercial upside Results support advancement into Phase 3 registrational trials and LAI development LAI – long acting injectable
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Agenda 01 Overview Abe Ceesay, Chief Executive Officer 02 RAP-219 in Drug-resistant Focal Onset Seizures Topline Phase 2a Data Jeff Sevigny, M.D., Chief Medical Officer 03 Closing Remarks Abe Ceesay 04 Questions and Answers Abe Ceesay | Jeff Sevigny | Troy Ignelzi, Chief Financial Officer 8
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9 Phase 2a trial in drug-resistant focal onset seizure patients 1. Drug-resistant focal onset seizures 2. RNS® probe implanted in seizure onset zone within mesial temporal lobe (MTL) ≥15 months before screening 3. Stable RNS System settings and other therapies 4. ≥16 LEs during 8-week retrospective review period 5. ≥1 clinical seizure reported during 8-week retrospective review period 6. >50% concordance between LEs and electrographic seizures RAP-219 Washout0.75 mg x 5 days then 1.25 mg QD 4-week Prospective Baseline 12-week pre-treatment period 8-week open-label treatment period 8-week follow-up period End of treatment End of trial Start of treatment Key Entry Criteria a Patients with no clinical seizures during the prospective baseline period were allowed to enter the treatment period. b LE baseline was defined as the 12 weeks preceding the initiation of treatment (the combination of the 8-week retrospective, and 4-week prospective baseline periods) LE – long episode; MTL – mesial temporal lobe; RNS System – responsive neurostimulator; QD – once daily Key Endpoints 8-week Retrospective Baseline Clinical seizure baselinea Long Episode (LE) baselineb • LE reduction (power determinations based on this outcome measure) • Proportion of patients with ≥30% reduction compared with LE baseline • Median percent change from LE baseline • Clinical seizure reduction • Proportion of patients with ≥50% reduction compared with pre- treatment baseline; proportion of patients who achieved seizure freedom • Median percent change from baseline
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→ Safety population (N = 30) → mITT population for LE efficacy (N = 27) • Safety population minus 2 patients with <3 weeks of treatment and 1 patient with RNS setting change → mITT-CS population for clinical seizure efficacy (N=25) • mITT population minus 2 patients who did not have clinical seizures during prospective baseline 10 Patient disposition and analysis populations 30 Dosed with RAP-219 26 Completed Treatment Period 4 Discontinued Treatment • Adverse event (n=3) • Other (n=1) 38 Assessed for Eligibility 8 Excluded • Did not meet eligibility criteria (n=7) • Adverse event (n=1) Analysis Populations mITT – patients with ≥3 weeks or treatment, ≥70% adherence, and no RNS system detection or stimulation setting changes. mITT-CS – mITT with clinical seizures in prospective baseline. LE – long episode; RNS System – responsive neurostimulator.
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Patient demographic and baseline characteristics 11 Highly drug-resistant FOS patients are representative of those in registrational trials a ASMs in ≥20% of patients. ASM – maintenance baseline antiseizure medication; FOS – focal onset seizures; RNS System – responsive neurostimulator; SD – standard deviation; MTL – mesial temporal lobe Safety Population N=30 Age, years; mean (SD) 40.1 (10.4) Age at first seizure, years; mean (SD) 16.6 (9.4) Sex, male; n (%) 18 (60%) Years since RNS implantation; median (range) 4.6 (2-11) Number of patients with a lead outside of MTL (n) 5 No. of concomitant ASMs Median (range) 3 (1-4) 1, n (%) | 2, n (%) | 3, n (%) | 4, n (%) 2 (7%) | 7 (23%) | 14 (47%) | 7 (23%) Most frequently used ASMsa, n (%) Lamotrigine 15 (50%) Levetiracetam 12 (40%) Cenobamate 11 (37%) Zonisamide 9 (30%) Clobazam 7 (23%) Lacosamide 7 (23%)
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12 Efficacy analyses → Efficacy analyses for 8-week treatment period: • mITT population (N=27) for long episodes • mITT-CS population (N=25) for clinical seizures → 8-week follow-up period currently ongoing; full data will be presented at future medical meetings
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Primary endpoints achieved with high statistical significance 71% reduction in long episodes (LEs); 85.2% responder rate (≥30% LE reduction) a Median percent change statistical comparison used the Wilcoxon signed rank test to determine if the % change in LE was greater than 0%. b Responder analysis statistical comparison was based on a one-sample exact test to determine whether the proportion of responders is >10%. c Statistical comparisons were not made for other cut points. 95% confidence intervals for responder analysis -- Clopper- Pearson exact binomial: ≥50%, (61.9, 93.7); ≥75%, (28.7, 68.1); 100%, (0.9, 24.3). d Concordance at baseline was determined by an independent epileptologist reviewer. LEs – long episodes Weeks 1-8, N=27 Percent change Responder analysis 48 LEs at baseline (median, per 28 days); 92% electrographic seizure / LE concordanced 13
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10 clinical seizures at baseline (median, per 28 days) Clinical seizure secondary endpoints achieved with statistical significance 14 77.8% clinical seizure reduction; 72% achieved clinically meaningful response (≥50% reduction) a Statistical comparison for median percent change used the Wilcoxon signed-rank test to determine if the median % reduction from baseline in CS was greater than 20%. Responder analysis statistical comparison is based on a one sample exact test to determine whether the proportion of responders is, (b) >20%; (c) >7%; (d) >1.5% for the 50% responder, 75% responder, and seizure freedom groups, respectively. CS – clinical seizures. Responder analysis Percent change Seizure Freedom (weeks 1-8) Weeks 1-8, N=25
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RAP-219 was generally well tolerated 15 TEAEs: 79% were mild, 10% discontinuation rate TEAE – treatment emergent adverse event during treatment period; ECG – electrocardiogram. Safety Population (N=30) Any TEAE, n (%) 25 (83.3%) TEAE leading to study drug discontinuation 3 (10.0%) Grade 1 TEAE - Mild 15 (50.0%) Grade 2 TEAE - Moderate 10 (33.3%) Grade ≥3 TEAE - Severe 0 TEAEs reported in ≥10% of patients, n (%) Dizziness 8 (26.7%) Headache 5 (16.7%) Fatigue 4 (13.3%) Fall 3 (10.0%) Nausea 3 (10.0%) Somnolence 3 (10.0%) TEAE SUMMARY → 25 patients reported a total of 65 TEAEs • 78.5% were mild, 21.5% were moderate • No serious adverse events or clinically significant laboratory, vital signs, or ECG abnormalities → 3 (10%) patients discontinued RAP-219 due to TEAEs • Grade 1 worsening of preexisting memory impairment • Grade 1 panic attack • Grade 2 worsening of preexisting anxiety
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16 Robust Phase 2a results support advancing program → Treatment with RAP-219 resulted in statistically significant reductions from baseline in long episodes and clinical seizures → RAP-219 was generally well-tolerated → Ease of use with once daily dosing, low risk of drug-drug interactions, and long half-life → Next steps: • End of Phase 2 FDA meeting planned 4Q 2025 • Phase 3 trials initiation planned 3Q 2026 • Progressing registrational/NDA enabling activities
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Agenda 01 Overview Abe Ceesay, Chief Executive Officer 02 RAP-219 in Drug-resistant Focal Onset Seizures Topline Phase 2a Data Jeff Sevigny, M.D., Chief Medical Officer 03 Closing Remarks Abe Ceesay 04 Questions and Answers Abe Ceesay | Jeff Sevigny | Troy Ignelzi, Chief Financial Officer 17
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Precision neuroscience pipeline with opportunity to address large market opportunities a IND is currently on clinical hold with the FDA. AMPAR – α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor; nAChR – nicotinic acetylcholine receptor. Category Program Discovery Preclinical Phase 1 Phase 2 Phase 3 Next Expected Milestones RAP-219 TARPγ8 AMPAR Programs Focal Onset Seizures End-of-Phase 2 FDA Meeting 4Q 2025 Phase 3 Trials Begin 3Q 2026 Bipolar Mania Topline Results 1H 2027 Diabetic Peripheral Neuropathic Pain Trial Initiationa Long-acting Injectable Formulation Formulation Nomination nAChR Discovery Programs α6 Chronic Pain Development Candidate Nomination α9α10 Hearing Disorders Development Candidate Nomination Strong intellectual property with worldwide rights to all programs Topline Results - September 8, 2025 Trial Underway 18
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19 Multiple anticipated catalysts over next 24 months 2H 2025 RAP-219 FOS open label extension trial initiation 3Q 2025 RAP-219 bipolar mania Phase 2 trial initiation 2027 2026 2025 2026 RAP-219 FOS Phase 2a additional efficacy analyses and 8-wk follow-up results 3Q 2026 RAP-219 FOS two Phase 3 trials initiation 1H 2027 RAP-219 bipolar mania Phase 2 topline results 2H 2026 RAP-219 FOS open label extension interim results FOS – focal onset seizures; PK – Pharmacokinetics. 2027 RAP-219 long- acting injectable initial PK results Cash balance of $260.4mma (as of 6/30/25) supports Rapport through end of 2026 a Cash, cash equivalents and short-term investments, excluding restricted cash.
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20 Emerging best-in-class profile for RAP-219 in focal onset seizures, with multi-billion dollar commercial opportunity, if approved Efficacy Data Phase 2a results demonstrated statistically significant reductions in long episodes and clinical seizures Tolerability Data RAP-219 was generally well-tolerated in Phase 2a Ease of Use Once daily dosing, low risk of drug-drug interactions, rational polypharmacy potential, and long half- life Long-acting Injectable Advancing first ever LAI for epilepsy patients, providing IP extension leading to potential commercial upside Results support advancement into Phase 3 registrational trials and LAI development LAI – long acting injectable
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Agenda 01 Overview Abe Ceesay, Chief Executive Officer 02 RAP-219 in Drug-resistant Focal Onset Seizures Topline Phase 2a Data Jeff Sevigny, M.D., Chief Medical Officer 03 Closing Remarks Abe Ceesay 04 Questions and Answers Abe Ceesay | Jeff Sevigny | Troy Ignelzi, Chief Financial Officer 21
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Thank you