Rapport Therapeutics, Inc. · NASDAQ:RAPP
Rapport Therapeutics — Investor Presentation (April 2026)
50 slides from Rapport Therapeutics's investor presentation, Apr 21, 2026
Slide 1: April 2026 Corporate Presentation
April 2026 Corporate Presentation
Slide 2: Forward-looking statements
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,” “pot
Slide 3: Leadership with track record of innovation and expertise
Leadership with track record of innovation and expertise Reid Huber, Ph.D. Director Partner, Third Rock Ventures; CEO, Merida Biosciences James Healy, M.D., Ph.D. Director Managing Partner, Sofinnova Investments Wendy Young, Ph.D. Director Former Head of Small Molecule Drug Discovery, Genentech Stev
Slide 4: Strong Foundation and Differentiated Precision Approach
Strong Foundation and Differentiated Precision Approach Small molecule precision medicines for patients with neurological and psychiatric disorders TARP8: transmembrane AMPA regulatory protein gamma-8; AMPAR: α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. 1 Includes cash, ca
Slide 5: Advancing precision therapeutics aimed at solving long-standing challenges in neuromedicine
Advancing precision therapeutics aimed at solving long-standing challenges in neuromedicine Drugs interact with receptors that are ubiquitous in the brain and body Drugs not designed with precision for disease-specific neuroanatomic sites / receptors Drug interactions and adverse events lead to nonc
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 RAP-219 TARPγ8 AMPAR Focal Onset Seizures Phase 3 Initiation 2Q 2026 Primary Generalized Tonic-Clonic Seizures Phase 3 Initiation 1H 2
Slide 7: RAP-219 pipeline-in-a-product supports long term growth runway
Primary Generalized Tonic-Clonic Seizures ~0.8 million patients ~$7B marketa RAP-219 pipeline-in-a-product supports long term growth runway Focal Onset Seizures 1.8 million patients ~$15B marketa Bipolar Mania ~1.5 million patients ~$40B market Long-acting Injectable Durable revenue across all indic
Slide 8: Unmet need in epilepsy highlights limitations of current antiseizure medications
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
Slide 9: RAP-219 selectively binds to TARPγ8
RAP-219 selectively binds to TARPγ8, representing a potential first-in-class precision medicine for neurological and psychiatric disorders AMPA type glutamate receptors at excitatory synapses can mediate the initiation and propagation of seizures AMPA Receptors (AMPAR) in Epilepsy TARPs regulate the
Slide 10: MTL and cerebral cortex are key brain areas in focal onset seizures
MTL and cerebral cortex are the key brain areas associated with focal onset seizures PET results confirm TARPγ8 is highly expressed in the MTL and neocortex RAP-219 target, TARPγ8, is selectively expressed in brain regions where focal onset seizures originate TARPγ8 Clinical PETa High expression in
Slide 11: 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 Robust, dose-dependent seizure protection observed in gold-standard preclinical model Epilepsy Model Corneal kindling – mousea PTZ - mousea Rota
Slide 12: RAP-219 dose-exposure-RO relationship
RAP-219 dose-exposure-RO relationship Preclinical models demonstrated maximal seizure protection at 50-70% RO (green band) All Phase 3 FOS trial doses achieve target RO RO: Receptor occupancy.
Slide 13: RAP-219 in Focal Onset Seizures
RAP-219 in Focal Onset Seizures 13
Slide 14: Phase 2a proof-of-concept trial in FOS patients
Phase 2a proof-of-concept trial in FOS patients with an objective electrographic biomarker for clinical seizure reduction FDA-approved device for patients with drug-resistant focal onset seizures Two probes implanted into regions of the brain known to have epileptiform activity Probes continuously d
Slide 15: Phase 2a trial in drug-resistant focal onset seizure patients
Phase 2a trial in drug-resistant focal onset seizure patients Drug-resistant focal onset seizures RNS® probe implanted in seizure onset zone within mesial temporal lobe (MTL) ≥15 months before screening Stable RNS System settings and other therapies ≥16 LEs during 8-week retrospective review period
Slide 16: Patient disposition and analysis populations
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 prosp
Slide 17: Patient demographic and baseline characteristics
Patient demographic and baseline characteristics Highly drug-resistant FOS patients are representative of those in registrational trials aMaintenance ASMs in ≥20% of patients at baseline. ASM – antiseizure medication; FOS – focal onset seizures; MTL – mesial temporal lobe; RNS – responsive neurostim
Slide 18: 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 18
Slide 19: 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) 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
Slide 20: Clinical seizure secondary endpoints achieved with statistical significance
10 clinical seizures at baseline (median, per 28 days) Clinical seizure secondary endpoints achieved with statistical significance 77.8% clinical seizure reduction; 72% achieved clinically meaningful response (≥50% reduction) a Statistical comparison for median percent change used the Wilcoxon signe
Slide 21: Clinically meaningful improvement regardless of baseline disease severity
Clinically meaningful improvement demonstrated, regardless of baseline disease severity Long Episode Responder Rates Response Threshold Response Threshold Response Threshold Response Threshold Proportion of Patients Proportion of Patients Proportion of Patients Proportion of Patients ≤48 Long Episod
Slide 22: RAP-219 reduced LEs and clinical seizures during early and late treatment
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 Time Period Time Period Median Percent Reduction Median Percent Reduction 22 Motley et al, American Epile
Slide 23: Observed RAP-219 mean plasma concentrations
aRAP-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. Treatment Perioda Follow-Up Period Observed RAP-219 mean plasma concentrations 22-day half-life results in concentrations above target 50% RO throughout follow-up
Slide 24: 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 Median percent change statistical comparisons used the Wilcoxon signed-rank test to determine if the median percentage change in LE from baseline was greater than
Slide 25: 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 Median percent change statistical comparisons used the Wilcoxon signed-rank test to determine if the median percentage change in CS from baseline was gre
Slide 26: Sustained treatment effect of RAP-219 over weeks
Sustained treatment effect of RAP-219 over 16 weeks, consistent with RAP-219’s long half-life and sustained exposures Treatment Period Weeks 1-8 Weeks 1-12 (Treatment Period Weeks 1-8 and Follow-up Period Weeks 9-12) Weeks 1-16 (Treatment Period Weeks 1-8 and Follow-up Period Weeks 9-16) Long Episod
Slide 27: RAP-219 was generally well tolerated
RAP-219 was generally well tolerated 10% discontinuation rate due to TEAEs Safety Population Treatment Period Weeks 1–8 (N=30) Follow-Up Period Weeks 9–16 (N=30) Any TEAE, n (%) 25 (83.3) 10 (33.3) TEAE related to study drug 23 (76.7) 2 (6.7) TEAEs by grade Grade 1 TEAE (mild) 15 (50.0) 7 (23.3) Gra
Slide 28: Strong interest from both epileptologists and neurologists
Strong interest from both epileptologists and neurologistsa Highly favorable HCP reception to RAP-219 profile The magnitude of seizure reduction (78%) and seizure freedom at 8 weeks (24%) repeatedly cited as meaningful and key differentiators Stated desire for early-line use Emerging best-in-class p
Slide 29: Phase 2a data support advancement into Phase 3 FOS registrational trials
Phase 2a data support advancement into Phase 3 FOS registrational trials Topline results reported September 2025; additional analyses presented at Annual Epilepsy Society (AES) meeting Successfully completed end-of-Phase 2 (EOP2) FDA meeting in December 2025 Initiated open-label, long-term safety tr
Slide 30: RAP-219 Phase 3 clinical trials in FOS
Start of Baseline Population Drug-resistant FOS N = ~320 in each trial Dosing Levels, Duration of Treatment and Follow-up Evaluating 3 doses, representing RO from 50-85% 12-week maintenance treatment period following titration 8-week follow-up period (or rollover to open-label extension) Open-label
Slide 31: Expanding RAP-219 into Primary Generalized Tonic-Clonic Seizures
Expanding RAP-219 into Primary Generalized Tonic-Clonic Seizures (PGTCS) 31
Slide 32: Opportunity for highly differentiated PGTCS treatment
Opportunity for highly differentiated PGTCS treatment Few treatment options with limited efficacy: ~6 drugs approved for PGTCS; 30-40% drug-resistance Potential for SAEs: liver failure, SJS, DRESS, QT prolongation Mortality risk: uncontrolled PGTCS increase SUDEP risk Today’s Standard of Care SJS -
Slide 33: RAP-219 Life Cycle Extension through Long-acting Injectable
RAP-219 Life Cycle Extension through Long-acting Injectable 33
Slide 34: Optimized LAI Formulation
Optimized LAI Formulation I think that it will be used, and if it works like the [RAP-219 target product profile] says, that's going to be a great advance for patients with epilepsy.” – US Neurologista “ RAP-219 properties are ideal for LAI formulation Candidate formulation achieved all phase-approp
Slide 35: RAP-219 LAI is an important lifecycle management opportunity
RAP-219 long-acting injectable (LAI) is an important lifecycle management opportunity Potential to transform epilepsy standard of care and offer new option for bipolar mania patients Improved adherence could facilitate greater protection against breakthrough seizures and prevention of bipolar mood r
Slide 36: RAP-219 in Bipolar Mania
RAP-219 in Bipolar Mania &} capport therapeutics 36
Slide 37: Bipolar mania is characterized by marked mood changes and increased energy
Inflated self-esteem or grandiosity Bipolar mania is characterized by episodes involving marked mood changes and increased energy Common Manic Episode Symptoms A single weeklong manic episode—or one requiring hospitalization—meets diagnostic criteria; disorder is considered lifelong, with most patie
Slide 38: Limitations of standard of care in bipolar mania
~50% of bipolar patients are treated with ASMs in combination with lithium at first-line or used second-linec Bipolar mania is a common psychiatric disease with significant need for well-tolerated, effective treatments Tolerability issues: metabolic and neurological side effects including weight gai
Slide 39: Glutamate and AMPA receptors in bipolar mania
Increased Cerebral Metabolism in Manic Patients Relative to Healthy Controls aJ.O. Brooks III et al. / Psychiatry Research: Neuroimaging 181 (2010) 136–140; Yüksel, C., & Öngür, D. (2010). Magnetic resonance spectroscopy studies of glutamate-related abnormalities in mood disorders. Biological Psychi
Slide 40: Phase 2 proof-of-concept trial in bipolar mania
Phase 2 proof-of-concept trial in bipolar mania End of Treatment End of Study Start of Treatment Day -7 to Day -1 1 Day 1 to Day 22 22 Day 22 to Day 77 1 Week 3 Weeks 8 Weeks Dischargea NCT07046494; aIf a participant does not meet all discharge criteria; the Investigator may reassess at their discre
Slide 41: nAChR Programs
nAChR Programs 41 α6β4 in Chronic Pain and Migraine α9α10 in Hearing and Vestibular Disorders
Slide 42: Use of RAPs enables targeting of diverse nicotinic receptors
Use of RAPs enables targeting of diverse nicotinic receptors α6β4 nAChR Expressed selectively in sensory neurons position it as a genetically-validated precision non-opiate non-CNS target for pain and migraine α9α10 nAChR Expressed selectively in auditory and vestibular and hair cells position it as
Slide 43: Selective α6β4 Agonist Exhibited Robust Activity in Preclinical Pain Models
Rapport Selective α6β4 Agonist (RTX) Exhibited Robust Activity in Preclinical Pain Models Peripheral nerve injury model Migraine model α6β4 nicotinic receptor: a precision non-opiate non-CNS target for pain relief
Slide 44: Market Opportunity & Milestones
Market Opportunity & Milestones 44
Slide 45: Growing epilepsy and neurological disorder franchise (U.S.)
Growing epilepsy and neurological disorder franchise (U.S.) 60% 1.8M Focal Onset Seizure Patients 30-40% Drug-resistant ~$15B market 25-35% ~0.8M Patients with PGTCS ~30-40% Drug-resistant ~$7B market 3.0M U.S. Epilepsy Patients (ages 18+) ~2.9M Diagnosed Patients ~1.5M Bipolar Mania Patients ~$40B
Slide 46: Multiple anticipated catalysts over next 24 months
Additional catalysts: α6β4 Phase 1 trial initiation 2027 2026 2025 2Q 2026 1H 2027 RAP-219 bipolar mania Phase 2 topline results 2H 2026 RAP-219 FOS open label extension initial data 2027 RAP-219 long-acting injectable Phase 1 topline results (PK) RAP-219 FOS Phase 3 program initiation 46 RAP-219 Ep
Slide 47: Appendix
Appendix
Slide 48: 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/CY
Slide 49: RNS measures and stores episode starts and long episodes in real time
RNS measures and stores episode starts and long episodes in real time, all the time EEG RNS Progression of epileptiform activity to clinical seizures Seizure Diary Clinical Seizures Electrographic Seizures Increased amplitude, spread, and persist Epileptiform discharges Clinical Seizures Long Episod
Slide 50: Relationship between long episode and clinical seizure responder rates
Well-established relationship between long episode and clinical seizure responder rates A Skarpaas et al., Epilepsy & Behavior 83 (2018); b Quraishi et al., Epilepsia 61 (2020); c Gammaitoni et al, American Epilepsy Society (AES) 2024 Annual Meeting, Poster #1.494. Skarpaas (2018)a: significant corr
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