Rapport Therapeutics, Inc. · NASDAQ:RAPP
Rapport Therapeutics — Investor Day (June 2025)
46 slides from Rapport Therapeutics's investor day presentation, Jun 2, 2025
Slide 1: Investor & Analyst Day June 2, 2025
Investor & Analyst Day June 2, 2025
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: Agenda
Agenda 01 Welcome and Introductions Abe Ceesay, Chief Executive Officer 02 RAP-219: Program Overview David Bredt, M.D., Ph.D., Founder, Chief Scientific Officer 03 RAP-219: Phase 1 Data | RAP-219: Phase 2a Focal Epilepsy Trial Overview Jeff Sevigny, M.D., Chief Medical Officer 04 Fireside Chat: KOL
Slide 4: Welcome and Introductions
01 Welcome and Introductions Abe Ceesay, Chief Executive Officer 02 RAP-219: Program Overview David Bredt, M.D., Ph.D., Founder, Chief Scientific Officer 03 RAP-219: Phase 1 Data | RAP-219: Phase 2a Focal Epilepsy Trial Overview Jeff Sevigny, M.D., Chief Medical Officer 04 Fireside Chat: KOL Perspec
Slide 5: 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 6: Company builders with industry-proven leadership
Company builders with industry-proven leadership Differentiated pharmacology we believe promotes high selectivity and specificity Potential to transform the treatment of neurological and psychiatric disorders with differentiated profile Strong Foundation & Differentiated Precision Approach Small mol
Slide 7: 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 8: Precision neuroscience pipeline with opportunity to address large market opportunities
Precision neuroscience pipeline with opportunity to address large market opportunities 1 IND is currently on clinical hold with the FDA; 2 nicotinic acetylcholine receptor. Note: We have conducted four Phase 1 trials supportive of multiple RAP-219 indications. Category Program Discovery Preclinical
Slide 9: RAP-219 enables "pipeline-in-a-product" opportunity
RAP-219 enables “pipeline-in-a-product” opportunity Internal Market Research, 2023 1 Diagnosed prevalence; 2 True prevalence (diagnosed prevalence divided by the diagnosis rate); 3 Diagnosed prevalence across diabetic peripheral neuropathy (~2.8 million), post-herpetic neuralgia (~1.8 million); trig
Slide 10: Unmet need in epilepsy highlights limitations of current antiseizure medications
Unmet need in epilepsy highlights limitations of current antiseizure medications 1 Refractory patients are those who continue to experience recurring seizures despite taking two or more ASMs; 2 Source: Epilepsy Foundation. Limitations of antiseizure medications (ASMs) 3.0M U.S. Epilepsy Patients (ag
Slide 11: Agenda: RAP-219 Program Overview
01 Welcome and Introductions Abe Ceesay, Chief Executive Officer 02 RAP-219: Program Overview David Bredt, M.D., Ph.D., Founder, Chief Scientific Officer 03 RAP-219: Phase 1 Data | RAP-219: Phase 2a Focal Epilepsy Trial Overview Jeff Sevigny, M.D., Chief Medical Officer 04 Fireside Chat: KOL Perspec
Slide 12: AMPAR inhibition is a clinically validated approach for epilepsy
AMPAR inhibition is a clinically validated approach for epilepsy ~50% of all focal onset seizures originate in the mesial temporal lobe (MTL), which includes the hippocampus and amygdala Most of the remaining 50% originate in the cerebral cortex and spread into the mesial temporal structures Focal o
Slide 13: TARP\u03b38 is selectively expressed in brain regions associated with focal onset seizures
NatComm 2022 13:734 GluA1 GluA2 TARP8 Western blot JCB 2003 161:805 STG γ-3 γ-4 γ-8 tubulin TARPγ8 clinical PET RAP-219 target/TARPγ8 is selectively expressed in brain regions associated with focal onset seizures TARPs regulate the trafficking, subcellular localization and gating of AMPA receptors
Slide 14: 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 15: Robust dose-dependent seizure protection in preclinical model for refractory focal epilepsy
Robust dose-dependent seizure protection observed in the gold standard pre-clinical model for refractory focal epilepsy Corneal Kindling Responders in Mice Robust, dose-dependent seizure protection observed at 50-70% receptor occupancy RAP-219 Plasma Concentration (ng/mL) Corneal Kindling Responders
Slide 16: Corneal kindling responders and rotarod failures in mice
% Corneal Kindling Responders RAP-219 Plasma Concentration (ng/mL) Corneal Kindling and Rotarod Failures (%) % Rotarod Failures Highly potent with no rotarod failures observed at highest exposure Corneal Kindling Responders and Rotarod Failures in Mice The Rotarod Performance Test is considered a go
Slide 17: RAP-219 precision has the potential to significantly improve the therapeutic index
RAP-219 precision has the potential to significantly improve the therapeutic index Therapeutic Index = TD50 (toxic dose) on Rotarod/ED50 (effective dose) for efficacy. 1 Data on file, Rapport Therapeutics; https://panache.ninds.nih.gov/;2 Data based on published reports from different preclinical st
Slide 18: TARP\u03b38 AMPAR NAMs active across a range of preclinical epilepsy models
TARPγ8 AMPAR NAMs active across a range of preclinical epilepsy models Preclinical epilepsy models are highly translatable, with probabilities of clinical success up to 70%, according to epileptologist Jacqueline French, MD Robust efficacy across a broad array of preclinical focal and generalized se
Slide 19: Agenda: RAP-219 Phase 1 Data
01 Welcome and Introductions Abe Ceesay, Chief Executive Officer 02 RAP-219: Program Overview David Bredt, M.D., Ph.D., Founder, Chief Scientific Officer 03 RAP-219: Phase 1 Data | RAP-219: Phase 2a Focal Epilepsy Trial Overview Jeff Sevigny, M.D., Chief Medical Officer 04 Fireside Chat: KOL Perspec
Slide 20: Phase 1 development: healthy volunteers exposed to RAP-219
Phase 1 development: 100 healthy volunteers exposed to RAP-219 Single dose up to 3 mg and multiple doses up to 1.75 mg SAD-101 8/cohort (6 active: 2 placebo) 01 MAD-102 8/cohort (6 active: 2 placebo) 02 PET-103 03 MAD-104 8/cohort (6 active: 2 placebo) 04 N=36* 3.0 mg 2.0 mg 1.0 mg 0.5 mg 0.25 mg Fo
Slide 21: Safety and tolerability of RAP-219 in Phase 1 multiple dose studies
TEAE SUMMARY All Grade 1 or 2 Tended to occur early in treatment and resolve without further action No SAEs or clinically significant laboratory, vital signs, or ECG abnormalities 3 discontinuations Safety and tolerability of RAP-219 in Phase 1 multiple dose studies Favorable profile in healthy volu
Slide 22: RAP-219 human PET study
RAP-219 human PET study TARP8 highly expressed in neocortex and mesial temporal lobe High expression of TARP8 in the neocortex and mesial temporal lobe (including hippocampus and amygdala), where nearly all focal onset seizures originate and relatively low expression in cerebellum, thalamus, and b
Slide 23: RAP-219 dose-exposure-RO relationship
RAP-219 dose-exposure-RO relationship Human PET RO data support lower dose levels, potentially increasing dose flexibility Preclinical models demonstrated maximal seizure protection at 50-70% RO (green band) Human target RO (50-70%) achieved at doses/exposures lower than predicted from animal models
Slide 24: RAP-219 summary
RAP-219 summary Phase 1 results provide strong support for further development of RAP-219 Generally well tolerated No SAEs; relatively low incidence of TEAEs; none greater than Grade 2 Consistent with target biology, no sedation observed Precision targeting of areas where focal onset seizures origin
Slide 25: Agenda: Phase 2a Focal Epilepsy Trial Overview
01 Welcome and Introductions Abe Ceesay, Chief Executive Officer 02 RAP-219: Program Overview David Bredt, M.D., Ph.D., Founder, Chief Scientific Officer 03 RAP-219: Phase 1 Data | RAP-219: Phase 2a Focal Epilepsy Trial Overview Jeff Sevigny, M.D., Chief Medical Officer 04 Fireside Chat: KOL Perspec
Slide 26: Phase 2a proof-of-concept trial in FOS patients with implanted RNS system
Phase 2a proof-of-concept trial in FOS patients with implanted RNS system Two probes implanted into regions of the brain known to have epileptiform activity Probes continuously detect and record epileptiform activity, including long episodes (LEs) & stimulate the region to attenuate seizure activity
Slide 27: 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 28: RNS system provides objective measure of epileptiform activity
RNS system provides objective measure of epileptiform activity and early signal of clinical response to ASMs Epilepsy & Behavior. 2018; 83: 192-200; Epilepsia. 2020; 61:138-148. “It could be argued that long episodes are an even better therapeutic target than reported clinical seizures.” “Changes in
Slide 29: Rationale for selecting LEs as primary endpoint
Rationale for selecting LEs as primary endpoint Well-established relationship between long episode and clinical seizure responder rates 1 Skarpaas et al., Epilepsy & Behavior 83 (2018); 2 Quraishi et al., Epilepsia 61 (2020); 3 Gammaitoni et al, American Epilepsy Society (AES) 2024 Annual Meeting, P
Slide 30: Phase 2a proof-of-concept trial in focal epilepsy patients
Phase 2a proof-of-concept trial in focal epilepsy patients KOL-guided, innovative study using validated biomarker of clinical seizures Medically refractory focal epilepsy RNS probe implanted in seizure onset zone within MTL ≥ 15 months before screening Stable RNS System settings and therapies ≥ 16 L
Slide 31: Preliminary baseline characteristics of Phase 2a trial patients
Preliminary baseline characteristics of Phase 2a trial patients Seizure frequency consistent with patients enrolled in registrational FOS trials Note: Preliminary baseline characteristics reflect the first 14 patients enrolled (those with final baseline data available as of May 20, 2025) from an unl
Slide 32: Agenda: Fireside Chat
Agenda 01 Welcome and Introductions Abe Ceesay, Chief Executive Officer 02 RAP-219: Program Overview David Bredt, M.D., Ph.D., Founder, Chief Scientific Officer 03 RAP-219: Phase 1 Data | RAP-219: Phase 2a Focal Epilepsy Trial Overview Jeff Sevigny, M.D., Chief Medical Officer 04 Fireside Chat: KOL
Slide 33: Fireside Chat: KOL Perspective
Fireside Chat: KOL Perspective Jacqueline French, M.D. Professor of Neurology, NYU Langone Jeff Sevigny, M.D. Chief Medical Officer
Slide 34: Agenda: Framing Future Data
01 Welcome and Introductions Abe Ceesay, Chief Executive Officer 02 RAP-219: Program Overview David Bredt, M.D., Ph.D., Founder, Chief Scientific Officer 03 RAP-219: Phase 1 Data | RAP-219: Phase 2a Focal Epilepsy Trial Overview Jeff Sevigny, M.D., Chief Medical Officer 04 Fireside Chat: KOL Perspec
Slide 35: RAP-219 Phase 2a trial in patients with focal epilepsy
RAP-219 Phase 2a trial in patients with focal epilepsy Goal: Generate data from ≥20 participants showing convincing reductions in long episodes and clinical seizures to support advancement to registrational studies
Slide 36: RNS electrographic biomarker data is a highly objective complement to seizure diary data
RNS electrographic biomarker data is a highly objective complement to clinical seizure diary data Each patient serves as case study with 12 weeks of baseline data, detailed pharmacodynamic measures of onset of effect, and depth of response Depth of response and responder proportion can offer strong
Slide 37: Responder rates in registrational trials of approved and pipeline ASMs
Responder rates in registrational trials of approved and pipeline ASMs ~25-55% of patients achieve a clinically meaningful ≥50% clinical seizure reduction in registrational trials for approved therapies Responder rates in this range result in statistically significant placebo-adjusted median percent
Slide 38: Key endpoints and anticipated topline data
Key endpoints and anticipated topline data Outcome Topline Data Long Episode Primary Endpoint Analysis LE frequency reduction responder analysis (% of patients that demonstrate ≥30% reduction in LEs compared with baseline)* Median percent change in LE frequency on treatment compared with baseline Cl
Slide 39: Targets for anticipated topline data
Targets for anticipated topline data Outcome RAP-219 Target Topline Data Long Episode Primary Endpoint Analysis LE frequency reduction responder analysis (% of patients that demonstrate ≥30% reduction in LEs compared with baseline)* ≥40% Median percent change in LE frequency on treatment compared wi
Slide 40: Agenda: Financial Update
01 Welcome and Introductions Abe Ceesay, Chief Executive Officer 02 RAP-219: Program Overview David Bredt, M.D., Ph.D., Founder, Chief Scientific Officer 03 RAP-219: Phase 1 Data | RAP-219: Phase 2a Focal Epilepsy Trial Overview Jeff Sevigny, M.D., Chief Medical Officer 04 Fireside Chat: KOL Perspec
Slide 41: Pipeline targets large market opportunities
Pipeline targets large market opportunities True Prevalence Bipolar disorder in U.S. patients2 ~7.2M Peripheral neuropathic pain in U.S. patients3 ~5.6M 1 Diagnosed prevalence; 2 True adult prevalence (diagnosed prevalence divided by the diagnosis rate); 3 Diagnosed prevalence across diabetic periph
Slide 42: Cash runway and anticipated catalysts
Cash runway and anticipated catalysts Cash balance of $285.4mm1 (as of 3/31/25) supports Rapport through end of 2026 1Cash, cash equivalents and short-term investments, excluding restricted cash. Sept 2025 RAP-219 Phase 2a trial in focal epilepsy topline results expected Q3 2025 RAP-219 Phase 2a tri
Slide 43: Questions & Answers
Questions & Answers
Slide 44: Agenda: Closing Remarks
Agenda 01 Welcome and Introductions Abe Ceesay, Chief Executive Officer 02 RAP-219: Program Overview David Bredt, M.D., Ph.D., Founder, Chief Scientific Officer 03 RAP-219: Phase 1 Data | RAP-219: Phase 2a Focal Epilepsy Trial Overview Jeff Sevigny, M.D., Chief Medical Officer 04 Fireside Chat: KOL
Slide 45: Rapport Therapeutics: investment summary
Rapport Therapeutics: investment summary RAP-219 precision designed to maximize efficacy while avoiding typical ASM adverse events Highly expressed in forebrain regions associated with seizures and minimal expression in hindbrain areas potentially associated with AEs Phase 2a FOS trial design improv
Slide 46: Thank you
Thank you