Rapport Therapeutics, Inc. · NASDAQ:RAPP
Rapport Therapeutics — Investor Presentation (August 2025)
32 slides from Rapport Therapeutics's investor presentation, Aug 7, 2025
Slide 1: Corporate Overview August 2025
Corporate Overview August 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: 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: 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 5: Advancing precision therapeutics aimed at solving long-standing challenges in neuromedicine
Advancing precision therapeutics aimed at solving long-standing challenges in neuromedicine RAPs are components of the broader neuronal receptor complexes and play critical roles in regulating receptor assembly and function RAPs serve as unique binding sites targetable by novel pharmacophores design
Slide 6: 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 7: 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 8: 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 9: 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 10: 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 11: 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 12: Robust dose-dependent seizure protection in gold standard preclinical model
Robust dose-dependent seizure protection observed in the gold standard pre-clinical model for focal onset seizures 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 13: Highly potent with no rotarod failures at highest exposure
% 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 14: 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 15: 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 16: 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 17: 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 18: 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 19: 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 20: 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 21: 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 22: 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 23: 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 24: RAP-219 Phase 2a trial in patients with focal onset seizures
RAP-219 Phase 2a trial in patients with focal onset seizures Goal: Generate data from ≥20 participants showing convincing reductions in long episodes and clinical seizures to support advancement to registrational studies
Slide 25: Phase 2a proof-of-concept trial in focal onset seizure patients
Phase 2a proof-of-concept trial in focal onset seizure patients KOL-guided, innovative study using validated biomarker of clinical seizures Drug-resistant focal onset seizure patients RNS probe implanted in seizure onset zone within MTL ≥ 15 months before screening Stable RNS System settings and the
Slide 26: 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 27: Key endpoints and targets for anticipated topline data
Key endpoints and 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 tre
Slide 28: Persistent unmet need highlights opportunity for innovation in bipolar mania treatment
Persistent unmet need highlights opportunity for innovation in bipolar mania treatment Unmet need in bipolar mania Bipolar disorder prevalence is ~2.8 percent of the adult population in the U.S. (7.2 million adults) Typically treated with antipsychotic medications as either monotherapy or in combina
Slide 29: Rationale for RAP-219 in bipolar mania
Rationale for RAP-219 in bipolar mania Hypermetabolism in bipolar patients with acute mania has been seen in the anterior cingulate and the hippocampus, which have high expression of TARPγ8 ASMs such as valproate, lamotrigine, and carbamazepine are approved to treat bipolar disorder The corneal kind
Slide 30: Phase 2 proof-of-concept trial in bipolar mania
Phase 2 proof-of-concept trial in bipolar mania Key Entry Criteria: Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of bipolar I disorder, with or without mixed features, with or without psychotic symptoms, as confirmed by the Structured Clinical Inte
Slide 31: 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 focal onset seizure tri
Slide 32: Thank you
Thank you
Rapport Therapeutics — Investor Presentation (August 2025) on 6ix