Rapport Therapeutics, Inc. · NASDAQ:RAPP
Rapport Therapeutics — Investor Presentation (August 2026)
51 slides from Rapport Therapeutics's investor presentation, August 2026
Slide 1: Corporate Presentation
Corporate Presentation August 2026
Slide 2: Disclaimer
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,”
Slide 3: Leadership with track record of innovation and expertise
Leadership with track record of innovation and expertise Management Team David Bredt, M.D., Ph.D. Abe Ceesaya Cheryl Gault Founder, Chief Scientific Officer Chief Executive Officer Chief Operating Officer 20+ years neuroscience drug discovery 15+ years commercial and executive 20+ years corporate st
Slide 4: Small molecule precision medicines for patients with neurological and psychiatric disorders
Small molecule precision medicines for patients with neurological and psychiatric disorders Strong Foundation RAP-219: Pipeline-in-a- Robust Clinical Well Financed to Address and Differentiated Product with Near-Term and Discovery Pipeline Large Market Opportunity Precision Approach Catalysts Ahead
Slide 5: Advancing precision therapeutics aimed at solving long-standing challenges in neuromedicine
Advancing precision therapeutics aimed at solving long-standing challenges in neuromedicine Conventional CNS Drug Discovery The Potential of RAPs RAPs are components of the broader neuronal Drugs interact with receptors that are receptor complexes and play critical roles in ubiquitous in the brain a
Slide 6: Precision neuroscience pipeline with opportunity to address large market opportunities
Precision neuroscience pipeline with opportunity to address large market opportunities Program Indication Preclinical Phase 1 Phase 2 Phase 3 Next Expected Milestone Focal Onset Seizures Phase 3 Initiated 2Q 2026 RAP-219 Primary Generalized Tonic-Clonic Seizures Phase 3 Initiation 1H 2027 TARPγ8 AMP
Slide 7: RAP-219 pipeline-in-a-product supports long term growth runway
RAP-219 pipeline-in-a-product supports long term growth runway Long-acting Injectable Bipolar Potential to double peak Primary Mania revenue across franchise Extends exclusivity into ~1.6 million patients Generalized ~$45B market late 2040s Tonic-Clonic Seizures ~0.8 million patients Focal Onset ~$7
Slide 8: Unmet need in epilepsy highlights limitations of current antiseizure medications
Unmet need in epilepsy highlights limitations of current antiseizure medications Limitations of Antiseizure Medications (ASMs) 60% Limited Efficacy: Despite over 30 FDA approved ASMs, 30-40% of patients are still drug-resistanta 1.8M Focal Onset Seizure Patients Tolerability Issues: Burdensome side-
Slide 9: RAP-219 target, TARPγ8, is selectively expressed in brain regions where focal onset seizures originate
RAP-219 target, TARPγ8, is selectively expressed in brain regions where focal onset seizures originate Focal Onset Seizure Origination and Propagation TARPγ8 Clinical PET Cerebral cortex High expression in the neocortex and mesial temporal lobe, where nearly all seizures originate Hippocampus Amygda
Slide 10: Robust activity of RAP-219 across a broad array of seizure models
Robust activity of RAP-219 across a broad array of seizure models established our early confidence Corneal Kindling Responders and Rotarod Failures in Mice Epilepsy Modela Corneal kindling – mouse Corneal Kindling and Rotarod Failures (%) 8 PTZ - mouse % Corneal Kindling Responders % Rotarod Failure
Slide 11: RAP-219 dose-exposure-receptor occupancy relationship
RAP-219 dose-exposure-receptor occupancy (RO) relationship • Preclinical models demonstrated maximal seizure protection at >50% RO (black horizontal line) • All Phase 3 FOS trial doses achieve target RO Ph3 high dose (1.25mg) Ph3 mid dose (0.75mg) Ph3 low dose (0.25mg) Ph2 dose (1.25mg) 11
Slide 12: RAP-219 in Focal Onset Seizures
RAP-219 in Focal Onset Seizures 12
Slide 13: Phase 2a proof-of-concept trial in FOS patients with an objective electrographic biomarker
Phase 2a proof-of-concept trial in FOS patients with an objective electrographic biomarker for clinical seizure reduction Neuropace RNS System® • FDA-approved device for patients with drug-resistant focal onset seizures • Two probes implanted into regions of the brain known to have epileptiform acti
Slide 14: Phase 2a trial in drug-resistant focal onset seizure patients
Phase 2a trial in drug-resistant focal onset seizure patients 8-week Open-Label 8-week 12-week Pre-treatment Period Treatment Period Follow-up Period 4-week 8-week Retrospective Prospective 0.75 mg x 5 days then 1.25 mg QD RAP-219 Washout Baseline Baseline Clinical Seizure Start of End of End of Bas
Slide 15: Patient disposition and analysis populations
Patient disposition and analysis populations 38 Assessed for Eligibility 8 Excluded • Did not meet eligibility criteria 30 Dosed with RAP-219 4 Discontinued Treatment • Adverse event (n=3) • Other (n=1) 26 Completed Treatment Period Analysis Populations → Safety population (N=30) → mITT population f
Slide 16: Patient demographic and baseline characteristics
Patient demographic and baseline characteristics Highly drug-resistant FOS patients are representative of those in registrational trials Safety Population N=30 Age, years, mean (SD) 40.1 (10.4) Age at first seizure, years, mean (SD) 15.8 (9.3) Sex, male, n (%) 18 (60) Years since RNS implantation, m
Slide 17: FOS efficacy analyses
FOS efficacy analyses → Efficacy analyses for 8-week treatment period: • mITT population (N=27) for long episodes • mITT-CS population (N=25) for clinical seizures 17
Slide 18: Primary endpoints achieved with high statistical significance
Primary endpoints achieved with high statistical significance 71% reduction in long episodes (LEs); 85.2% responder rate (≥30% LE reduction) Percent Change Responder Analysis Weeks 1-8, N=27 48 LEs at baseline (median, per 28 days); 92% electrographic seizure / LE concordance d aMedian percent chang
Slide 19: Clinical seizure secondary endpoints achieved with statistical significance
Clinical seizure secondary endpoints achieved with statistical significance 77.8% clinical seizure reduction; 72% achieved clinically meaningful response (≥50% reduction) Percent Change Responder Analysis Seizure Freedom (weeks 1-8) Weeks 1-8, N=25 10 clinical seizures at baseline (median, per 28 da
Slide 20: Observed RAP-219 mean plasma concentrations
Observed RAP-219 mean plasma concentrations 22-day half-life resulted in concentrations above target 50% RO throughout follow-up Treatment Perioda Follow-Up Period a RAP-219 0.75 mg/day for 5 days, followed by RAP-219 1.25 mg/day for the remainder of the 8-week treatment period. 20
Slide 21: Effect of RAP-219 on long episodes in follow-up period
Effect of RAP-219 on long episodes in follow-up period Significant and durable LE reduction, consistent with sustained RAP-219 exposures Treatment Period Follow-Up Period Median percent change statistical comparisons used the Wilcoxon signed-rank test to determine if the median percentage change in
Slide 22: Effect of RAP-219 on clinical seizures in follow-up period
Effect of RAP-219 on clinical seizures in follow-up period Clinically meaningful reduction in clinical seizures throughout treatment and follow-up Treatment Period Follow-Up Period Median percent change statistical comparisons used the Wilcoxon signed-rank test to determine if the median percentage
Slide 23: Sustained treatment effect of RAP-219 over 16 weeks
Sustained treatment effect of RAP-219 over 16 weeks, consistent with RAP- ’s long half-life and sustained exposures Weeks 1-12 Weeks 1-16 Treatment Period (Treatment Period Weeks 1-8 and (Treatment Period Weeks 1-8 and Weeks 1-8 Follow-up Period Weeks 9-12) Follow-up Period Weeks 9-16) Long Episodes
Slide 24: RAP-219 was generally well tolerated
RAP-219 was generally well tolerated 10% discontinuation rate due to TEAEs Treatment Period Follow-Up Period Weeks 1–8 Weeks 9–16 Safety Population (N=30) (N=30) TEAE Summary Any TEAE, n (%) 25 (83.3) 10 (33.3) → For AEs starting during the treatment period, TEAE related to study drug 23 (76.7) 2 (6
Slide 25: Emerging best-in-class profile potential for RAP-219 in FOS
Emerging best-in-class profile potential for RAP-219 in FOS, with commercial opportunity with >$2 billion in US, if approved Strong interest from both epileptologists and neurologists† Potential for Best-in- Generally Class Efficacy Well Tolerated • Highly favorable HCP reception to RAP-219 profile
Slide 26: Phase 2a data support advancement into Phase 3 FOS registrational trials
Phase 2a data support advancement into Phase 3 FOS registrational trials Initiated Phase 3 FOS program in 2Q 2026 • Two global, multi-center, placebo-controlled Topline results reported September 2025; clinical trials additional analyses presented at Annual • Traditional clinical seizure primary end
Slide 27: RAP-219 Phase 3 clinical trials in FOS
RAP-219 Phase 3 clinical trials in FOS 8-week Pre-treatment Period 14-week Treatment Perioda 8-week Post-treatment Period 1:1:1 Randomization 8-week Prospective RAP-219-FOS-301 – 1.25mg and 0.75 mg RAP-219 Follow-up Baseline RAP-219-FOS-302 – 0.75mg and 0.25 mg Placebo Start of Start of End of End o
Slide 28: Expanding RAP-219 into Primary Generalized Tonic-Clonic Seizures (PGTCS)
Expanding RAP-219 into Primary Generalized Tonic-Clonic Seizures (PGTCS) 28
Slide 29: Opportunity for highly differentiated PGTCS treatment
Opportunity for highly differentiated PGTCS treatment Today’s Standard of Care Potential for RAP-219 Few treatment options with limited efficacy: ~6 drugs approved for PGTCS; 30-40% drug-resistance Robust clinical data in FOS: 78% clinical seizure reduction Potential for SAEs: liver failure, SJS, DR
Slide 30: RAP-219 Life Cycle Extension through Long-acting Injectable
RAP-219 Life Cycle Extension through Long-acting Injectable 30
Slide 31: RAP-219 properties are ideal for long-acting injectable (LAI) formulation
RAP-219 properties are ideal for long-acting injectable (LAI) formulation Factors Driving Long-Acting Injectable Suitability RAP-219 LAI Formulation in Development for Once-Monthly Subcutaneous Administration Candidate formulation achieved all phase- Low Dose appropriate TPP attributes LAI provision
Slide 32: LAI commercial opportunity adds value to RAP-219
LAI commercial opportunity adds value to RAP-219 High interest in an LAI from HCPs and patients, seeing significant value add to SoC Franchise Benefits Desired Clinical Benefits RAP-219 Lifecycle Opportunity Focal onset epilepsy Lifecycle opportunity for RAP-219; expected to extend exclusivity Prote
Slide 33: RAP-219 in Bipolar Mania
RAP-219 in Bipolar Mania § rapport therapeutics 33
Slide 34: Bipolar mania is characterized by episodes involving marked mood changes and increased energy
Bipolar mania is characterized by episodes involving marked mood changes and increased energy A single weeklong manic episode—or one Common Inflated Manic self-esteem Episode Symptoms or grandiosity requiring hospitalization—meets diagnostic criteria; disorder is considered lifelong, with most Infla
Slide 35: Bipolar mania is a common psychiatric disease with significant need for well-tolerated, effective treatments
Bipolar mania is a common psychiatric disease with significant need for well-tolerated, effective treatments Limitations of Standard of Care ~3.6M Diagnosed Patients Tolerability issues: metabolic and neurological side effects including weight gain and cognitive impairment often lead to early discon
Slide 36: RAP-219 in bipolar mania has the potential to create significant value for patients
RAP-219 in bipolar mania has the potential to create significant value for patients Bipolar Mania Patient Flow Potential for RAP-219 US Adults with Bipolar Disorder ~3.6M • Strong HCP preference for RAP-219 early due to limitations of existing drugs Bipolar I (50% of diagnosed population) ~1.8M • Po
Slide 37: RAP-219 circuit-selective approach to bipolar mania
RAP-219 circuit-selective approach to bipolar mania Targets glutamatergic hyperactivity in cortico-limbic networks • Bipolar mania is characterized by increased glutamate levels and hypermetabolism in cortico- Increased Cerebral Metabolism in Manic limbic networksa,b,c Patients Relative to Healthy C
Slide 38: Phase 2 proof-of-concept trial in bipolar mania
Phase 2 proof-of-concept trial in bipolar mania 1 Week 3 Weeks 8 Weeks Up to 7 Day* 56 Day Safety Follow up Period 21 Day Treatment Period Screening Period Weekly Following Last Dose (*may be extended with MM approval) RAP-219 or Placebo Day -7 to Day -1 1 Day 1 to Day 22 22 Day 22 to Day 77 Start o
Slide 39: nAChR Programs
nAChR Programs α6β4 in Chronic Pain and Migraine α9α10 in Hearing and Vestibular Disorders 39
Slide 40: Use of RAPs enables targeting of diverse nicotinic receptors
Use of RAPs enables targeting of diverse nicotinic receptors • Pan nAChR agonists are clinically validated in pain RAP-641 – α6β4 nAChR Limitations of Standard of Care • A broad-spectrum nicotinic agonist (ABT-594a) a Expressed selectively in sensory neurons Preclinical and Clinical was effective in
Slide 41: RAP-641: α6β4 nicotinic receptor precision non-opiate non-CNS target for pain relief
RAP-641: α6β4 nicotinic receptor precision non-opiate non-CNS target for pain relief Rapport Selective α6β4 Agonist (RTX) Exhibited Robust Activity in Preclinical Pain Modelsa Peripheral nerve injury model Migraine model MMA vasodilation (% baseline) 1.50 Dose 2 1.25 PWT (g) 1 1.00 NTG 0 20 40 60 0
Slide 42: Market Opportunity & Milestones
Market Opportunity & Milestones 42
Slide 43: Growing epilepsy and neurological disorder franchise (U.S.)
Growing epilepsy and neurological disorder franchise (U.S.) Epilepsy Bipolar 60% ~3.6M 1.8M Focal Onset Diagnosed Patients Seizure Patients 3.0M ~8.0M U.S. Epilepsy Patients (ages 18+) 30-40% U.S. Bipolar Prevalence (ages 18+) Drug-resistant ~$15B market ~1.6M Bipolar Mania Patients 25-35% ~30-40% ~
Slide 44: Multiple anticipated catalysts over next 24 months
Multiple anticipated catalysts over next 24 months Cash balance of $436.1M (as of 6/30/26) supports Rapport into 2H 2029 RAP-219 Epilepsy Portfolio RAP-219 Phase 3 FOCUS 1 & FOCUS 2 trials initiated Oct 2026 1H 2027 RAP-219 FOS open-label long-term safety trial initiated RAP-219 bipolar RAP-219 PGTC
Slide 45: Appendix
tas Append
Slide 46: RAP-219 selectively binds to TARPγ8, representing a potential first-in-class precision medicine
RAP-219 selectively binds to TARPγ8, representing a potential first- in-class precision medicine for neurological and psychiatric disorders Cryogenic Electron Microscopy of AMPA Receptors (AMPAR) in Epilepsy GluA1/2 + TARPγ8 Complex K+ channel Action potential Na+ channel Na+ AMPAR Depolarization Pr
Slide 47: RAP-219 possesses potentially optimal drug properties for an ASM
RAP-219 possesses potentially optimal drug properties for an ASM Potency at TARPγ8 IC50 ~ 100 pM Selectivity vs. other TARPs, NMDAR >4,000X target affinity Selectivity vs. CEREP and kinase panels >10,000X target affinity PK Orally bioavailable | %F = 80-100 Brain penetration Brain/plasma ~70% DDI >1
Slide 48: Progression of epileptiform activity to clinical seizures
Progression of epileptiform activity to clinical seizures Epileptiform Increased amplitude, Electrographic Clinical discharges spread, and persist Seizures Seizures EEG RNS Seizure Diary Clinical Episode Starts Long Episodes / Electrographic Seizures Seizures RNS measures and stores episode starts a
Slide 49: Well-established relationship between long episode and clinical seizure responder rates
Well-established relationship between long episode and clinical seizure responder rates • Skarpaas (2018)a: significant correlation exists between reduction in long episodes and clinical seizure frequency • Quraishi (2020)b: ASMs resulting in a ≥ 20% decrease in long episodes were clinical efficacio
Slide 50: Clinically meaningful improvement demonstrated, regardless of baseline disease severity
Clinically meaningful improvement demonstrated, regardless of baseline disease severity Responder Rates by Baseline Severity Long Episode Responder Rates Clinical Seizure Responder Rates ≤ 8 Long Episodes >48 Long Episodes ≤ Clinical Seizures >10 Clinical Seizures N=14 N=13 N=13 N=12 100% 100% 100%
Slide 51: RAP-219 reduced LEs and clinical seizures similarly during early and late treatment periods
RAP-219 reduced LEs and clinical seizures similarly during early and late treatment periods Effect of RAP-219 During Treatment Weeks 1-4 and 5-8 Long Episode Reduction Clinical Seizure Reduction 100% 100% 85.0% 74.7% 74.7% 77.2% 77.8% 80% 80% 71.0% Median Percent Reduction Median Percent Reduction 6
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