false 0002012593 0002012593 2025-03-03 2025-03-03
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): March 3, 2025
Rapport Therapeutics, Inc.
(Exact name of Registrant as Specified in Its Charter)
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Delaware |
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001-42121 |
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88-0724208 |
(State or Other Jurisdiction of Incorporation) |
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(Commission File Number) |
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(IRS Employer Identification No.) |
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1325 Boylston Street Suite 401 |
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Boston, Massachusetts |
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02215 |
(Address of Principal Executive Offices) |
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(Zip Code) |
Registrant’s Telephone Number, Including Area Code: 857 321-8020
Not Applicable
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
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Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
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Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
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Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
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Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
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Title of each class |
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Trading Symbol(s) |
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Name of each exchange on which registered |
Common Stock, $0.001 par value per share |
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RAPP |
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The Nasdaq Global Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 7.01 |
Regulation FD Disclosure. |
On March 3, 2025, Rapport Therapeutics, Inc. (the “Company”) furnished its corporate presentation, attached as Exhibit 99.1 to this Current Report on Form 8-K in connection with the TD Cowen 45th Annual Health Care Conference today, March 3, 2025. The corporate presentation will also be available in the investor relations section of the Company’s website at www.rapportrx.com.
On March 3, 2025, the Company issued a press release announcing the appointment of Jeffrey Sevigny as Chief Medical Officer of the Company. A copy of this press release is furnished as Exhibit 99.2 to this Current Report on Form 8-K.
The information included under Item 7.01 of this Current Report on Form 8-K, including Exhibits 99.1 and 99.2, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, and shall not be incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
On March 3, 2025, the Company announced, in its corporate presentation, timeline updates with regards to its Phase 2a trials of RAP-219 in refractory focal epilepsy and bipolar mania. The Company is currently conducting a Phase 2a proof-of-concept trial in adult patients with refractory focal epilepsy, for which it expects to report topline results in the third quarter of 2025. The Company also intends to initiate an additional Phase 2a trial of RAP-219 in bipolar mania in the third quarter of 2025 with topline data expected in the first half of 2027.
Forward-Looking Statements
The information under this Item 8.01 contains “forward-looking statements” of the Company within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including without limitation, express or implied statements regarding: the clinical development of RAP-219 for the treatment of refractory focal epilepsy and bipolar mania and the expected timing of the results from ongoing clinical trials.
Forward looking statements in this Item 8.01 are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect the Company’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, including that interim, topline and preliminary data from our clinical trials that we announce or publish from time to time are subject to audit and verification procedures that could result in material changes in the final data; the Company’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; the Company’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 the Company’s intellectual property protections; and risks related to the competitive landscape for the Company’s product candidates; as well as other risks described in “Risk Factors,” in the Company’s Registration Statement on Form S-1, and most recent Quarterly Report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the Securities and Exchange Commission. The Company 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.
Item 9.01 |
Financial Statements and Exhibits. |
(d) Exhibits
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Cover Page Interactive Data File (embedded within the Inline XBRL document). |
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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Rapport Therapeutics, Inc. |
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Date: March 3, 2025 |
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By: |
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/s/ Troy Ignelzi |
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Troy Ignelzi |
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Chief Financial Officer
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Exhibit 99.1 Corporate overview March 2025

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,”
“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 drug-resistant focal epilepsy, peripheral neuropathic pain and bipolar disorder, including the initiation, timing, progress and results of our ongoing and
planned clinical trials; Rapport’s ability to resolve a clinical hold with the FDA; the potential activity and tolerability of RAP-219; the potential of Rapport’s RAP technology platform; the ongoing and planned development of RAP-199
and Rapport’s discovery-stage 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 Rapport’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; Rapport’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 Rapport’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 Rapport’s Registration Statement on Form S-1 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. 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

Leadership with track record of innovation and expertise Management Team
Board of Directors Steve Paul, M.D. James Healy, M.D., Ph.D. Reid Huber, Ph.D. John Maraganore, Ph.D. Robert Perez Founder and Board Chair Director Director Director Director Partner, Third Rock Ventures Managing Partner, Partner, Third Rock
Ventures; Former Founding CEO, Operating Partner, General Atlantic Sofinnova Investments CEO, Merida Biosciences Alnylam Former CEO, Cubist Pharmaceuticals Founder and Chairman, Life Science Cares Raymond Sanchez, M.D. Paul Silva Wendy Young, Ph.D.
Director Director Director Senior Advisor, Bain Life Sciences; Former Chief Accounting Officer, Former Head of Small Molecule Drug Former CMO, Cerevel Therapeutics Vertex Pharmaceuticals Discovery, Genentech 1 Employee director 3

Ushering in a new era of precision neuroscience Vision: To become a
leader in precision neuroscience through the discovery and development of transformational small molecule medicines for patients suffering from central nervous system (CNS) disorders Potential for differentiated Accomplished scientific innovators
Robust clinical & discovery Well financed approach to generate precision & company builders pipeline small molecule medicines Potential for first-in-class Road-tested capability of Pioneering programs leveraging receptor $320.7 million as of
identifying key mediators of 2 discovery team associated protein (RAP) September 30, 2024 receptor function science RAP-219 clinical program Cash runway expected to fund Differentiated pharmacology Non-sedative forebrain restricted Company builders
with 1 operations through end of we believe promotes high TARPγ8 AMPAR modulator – industry-proven leadership 2026, including multiple selectivity and specificity significant opportunity in initial development catalysts indication in
focal epilepsy Potential to transform the Discovery programs treatment of neurological Medicinal chemistry-enabled disorders with portfolio with potential in differentiated profile additional indications 1 AMPAR
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors 2 Includes cash, cash equivalents, and short-term investments, excluding restricted cash 4

We believe the current state and limitations of neuromedicine compels
the creation of Rapport RAPs are components of the broader neuronal receptor complexes and play critical roles in regulating receptor assembly and function Conventional CNS drug discovery The potential of RAPs Drugs interact with receptors that are
RAPs serve as unique binding sites targetable by ubiquitous in the brain and body novel pharmacophores designed for increased selectivity Drugs not designed with precision for disease- RAP targeting can provide tissue / neuroanatomical specific
neuroanatomic sites / receptors specificity RAPs enable differentiated pharmacology and Drug interactions and adverse events lead to potentially provide optimal efficacy, safety, and noncompliance and discontinuation administration profiles Drug
discovery with conventional approaches RAPs can “unlock” drug targets previously (lacking RAPs) can miss high potential, previously inaccessible to study in vitro, allowing for unexplored targets potentially first-in-class drug discovery
programs 5

Advancing our precision neuroscience pipeline to potentially address
large market opportunities Next Expected Category Program Discovery Preclinical Phase 1 Phase 2 Phase 3 Milestone Refractory Focal Topline Results Q3 2025 Trial Underway Epilepsy RAP-219 Trial Initiation Q3 2025 Bipolar Mania TARPγ8 AMPAR
Topline Results 1H 2027 Programs Diabetic Peripheral Trial Initiation* Neuropathic Pain α6 Development Candidate Chronic Pain nAChR Discovery Programs α9α10 Development Candidate Hearing Disorders Strong intellectual property with
worldwide rights to all programs Note: We have conducted two Phase 1 trials supportive of multiple RAP-219 indications * Subject to resolution of clinical hold with the FDA 6

Focal epilepsy is a large market with high unmet need Key highlights of
U.S. focal epilepsy market Limitations of current therapies U.S. Epilepsy Patients Limited Efficacy: Despite over >20 FDA approved x 3.0M anti-seizure medications (ASMs), 30-40% of (ages 18+) 1 patients are drug-resistant Tolerability Issues:
Especially CNS side-effects, x % Focal Epilepsy 60% such as sedation, ataxia, and cognitive problems Potential for Serious Adverse Events: Such as x Focal Epilepsy Patients 1.8M severe cutaneous reactions, serious hematological disorders, and
hepatic failure 1 Complicated Administration: Long titration, drug- x % Drug-Resistant 30-40% drug interactions, and lab monitoring 1 Drug-resistant patients are those who continue to experience recurring seizures despite taking two or more ASMs
Internal Market Research, 2023 7

RAP-219 is a “pipeline in a product” opportunity Focal
epilepsy Peripheral neuropathic pain Bipolar disorder 1 2 3 U.S. patients: 1.8 million U.S. patients: ~5.6 million U.S. patients: ~7 million TARPγ8 is a preclinically and clinically validated target for epilepsy Once daily (QD) dosing | No
evidence of sedation or motoric impairment | No observed drug-drug interactions (DDI) Compelling data supporting potential in peripheral neuropathic pain and bipolar disorder Long acting injectable (LAI) opportunity Potency and metabolic profile
positions RAP-219 as the first potential ASM in a depot formulation 1 2 Internal Market Research, 2023. Diagnosed prevalence. Diagnosed prevalence across diabetic peripheral neuropathy (~2.8 million), post-herpetic neuralgia (~1.8 3 million),
trigeminal neuralgia (~1.0 million). True prevalence (diagnosed prevalence divided by the diagnosis rate) 8

RAP-219 overview A. Mechanism of action and preclinical development B.
Phase 1 trials C. Phase 2a proof-of-concept trial in refractory focal epilepsy D. Bipolar mania and diabetic peripheral neuropathic pain 9

AMPAR inhibition is a clinically validated approach for epilepsy
Hippocampus and cortex are important sites of AMPA receptors (AMPAR) in epilepsy focal onset seizure origination ISBN 978-0-07-129621-6 • AMPA type glutamate receptors at excitatory • Approximately 50% of all focal onset seizures
synapses can mediate seizure initiation and originate in the mesial temporal lobe, which includes spread the hippocampus and amygdala. • AMPAR target is clinically validated - perampanel • Most of the remaining 50% originate in the
® (FYCOMPA ) is an FDA/EMA approved pan- cerebral neocortex and often spread into and are AMPAR antagonist for the treatment of focal propagated by the mesial temporal structures. onset and generalized seizures 10

Transmembrane AMPA regulatory proteins (TARPs) TARPs: Auxiliary
subunits that associate with AMPA receptors in the brain Crucial for regulating the trafficking, subcellular localization and gating of AMPA receptors Western Blot Cryogenic electron microscopy of TARPγ8 clinical PET GluA1/2 + TARPγ8
complex STG GluA1 γ-3 GluA2 TARPγ8 γ-4 γ-8 NatComm 2022 13:734 tubulin JCB 2003 161:805

RAP-219 observed to be highly potent and selective TARPγ8 AMPAR
NAM RAP-219 potency and selectivity TARPγ8-containing AMPA receptors (IC ) ~100 pM 50 vs. AMPA receptors (GluA1) lacking TARPs >100,000x vs. AMPA receptors containing other TARPs (γ2, γ3, γ4, γ7) >4,000x vs. NMDA
receptors (2A, 2B, 2D) >500,000x vs. GPCRs/ion channels/enzymes (panel of 52) >10,000x vs. kinases (panel of 373) >100,000x NAM = Negative allosteric modulator 12

Differentiated precision preclinical profile of RAP-219 Corneal
kindling responders and Receptor occupancy (%) in rats rotarod failures in mice EC % Corneal Kindling Responders 70 % Rotarod Failures 7 ng/mL • Oral administration of RAP-219 (0.001-10 mg/kg) • Valid model in focal epilepsy •
Plasma EC ’s of 7 ng/mL in rats (shown above) and • Oral administration of RAP-219 resulted in significant seizure 70 plasma EC ’s of 3 ng/mL in mice reduction in kindled mice at low plasma levels (<7 ng/mL) 70 corresponding to
a projected 50-70% receptor occupancy (RO) • No motoric impairments observed at highest doses tested EC = effective concentration achieving 70% occupancy of target receptor 70 13

RAP-219 precision has the potential to significantly improve the
therapeutic index Corneal kindling mouse model therapeutic index 160 >150 1 2 (TD rotarod/ED efficacy) for RAP-219 and other ASMs 50 50 140 120 100 80 60 >44 40 25 20 9.5 5.6 5.5 5.3 4.9 > 4.6 3.1 <2.3 1.3 0 Therapeutic Index = TD (toxic
dose) on Rotarod/ED (effective dose) for efficacy 50 50 1 Data on file, Rapport Therapeutics; https://panache.ninds.nih.gov/ 2 Data are based on published reports from different preclinical studies at different points in time, with differences in
preclinical study design and subject population. 14 As a result, cross-study comparisons cannot be made. No head-to-head studies have been conducted. Therapeutic Index

TARPγ8 NAM effectiveness persists with repeat dosing Antiseizure
activity maintained after prolonged exposure Corneal Kindling Responders (%) • Efficacy in corneal kindling used to evaluate RTX-1738 (an analog of RAP- 219) • RTX-1738 (3 mg/kg) tested following either single day or seven consecutive
days of oral administration • Antiseizure activity was maintained or became more potent after 7-day dosing Single oral administration, tested 2 hours post dose Seven-day oral administration, tested 2 hours after last dose 15

TARPγ8 AMPAR NAMs active in preclinical epilepsy models
Preclinical epilepsy models are highly translatable, with probabilities of clinical success up to 70%, according to epileptologist Jackie French • Robust efficacy across a broad array of preclinical Model focal and generalized seizure models *
Corneal Kindling – mouse • Potent activity in kindling model has been observed to * PTZ - mouse predict efficacy in focal epilepsy * Rotarod • Activity not seen in maximal electroshock (MES) Amygdala kindling – mouse model,
consistent with performance of levetiracetam and some other effective ASMs Hippocampal kindling – mouse 6Hz stimulation – mouse Chronic seizure models [like corneal kindling] offer Frings audiogenic seizure – mouse the most
etiologically relevant platform on which to accurately replicate clinical epilepsy and are thus GAERS absence epilepsy – rat deserving of more use earlier in ASD identification.” – Barker-Haliski, Expert Opinion on Drug Discovery *
Used RAP-219; where not noted, used other TARPγ8 NAM CNS & Neurological Disorders - Drug Targets (2017) 16:1099; J Pharmacol Exp Ther (2016) 357:394; J Amer Soc for Exper NeuroTherapeutics (2007) 4:12; Jackie French AES Presentation,
Professor, Neurology, NYU Grossman School of Medicine; Director, The Epilepsy Study Consortium (TESC); Barker-Haliski, M. (2019) Expert Opinion on Drug Discovery, 14(10), 947–951. 16

RAP-219 overview A. Mechanism of action and preclinical development B.
Phase 1 trials C. Phase 2a proof-of-concept trial in refractory focal epilepsy D. Bipolar mania and diabetic peripheral neuropathic pain 17

RAP-219 first-in-human Phase 1 trials PET receptor occupancy trial
Single ascending dose (SAD) trial (RAP-219-103) (RAP-219-101) • Open label, multiple dose trial in healthy volunteers • Randomized, double-blind, placebo-controlled SAD • Objective: confirm neuroanatomical expression of and open
label food effect study TARPγ8 and establish relationship between PK and • Objective: evaluate safety and tolerability brain target receptor occupancy (RO) • 5 cohorts, n=8 per cohort (6 active & 2 placebo) • 3 cohorts,
n=3-6 per cohort • 0.25 mg QD to 3 mg QD doses • 0.25 mg QD to 1.25 mg QD doses; over 14 days Multiple ascending dose trial (MAD-1) Multiple ascending dose trial (MAD-2) (RAP-219-102) (RAP-219-104) • Randomized, double-blind,
placebo-controlled MAD • Randomized, double-blind, placebo-controlled MAD • Objective: evaluate safety and tolerability with dose • Objective: evaluate safety and tolerability with escalation continued dose escalation and shorten
time to • 5 cohorts, n=8 per cohort (6 active & 2 placebo) reach predicted therapeutic levels • Up to 1.25 mg QD doses; over 2 to 4 weeks • 3 cohorts, n=8 per cohort (6 active & 2 placebo) • Up to 1.75 mg QD doses; up
to 28 days 18

RAP-219 Phase 1 experience 100 healthy volunteers exposed to RAP-219
Data underscore the potential broad therapeutic index, differentiated tolerability profile, and dosing flexibility of RAP-219 RAP-219 tolerability • RAP-219 was generally well tolerated with no SAE’s and no TEAEs greater than Grade 2
• Unlike with many anti-seizure medications, no sedation or motoric impairments were observed, consistent with target biology and preclinical observations • Three treatment discontinuations occurred (3%) that were attributed to TEAEs
RAP-219 receptor occupancy • PET trial confirmed restricted neuroanatomical expression of TARPγ8 • RAP-219 achieved and exceeded target RO associated with maximal efficacy in preclinical models (50%-70%), while maintaining a
differentiated tolerability profile • Target RO can be achieved within five days of dosing SAE = Serious adverse event; TEAE = Treatment emergent adverse events; ECG= electrocardiogram 19

RAP-219 Phase 1: PET trial results RAP-219 achieved and exceeded target
RO and was generally well tolerated Restricted neuroanatomical expression of TARPγ8 was confirmed TARPγ8 clinical PET • TARPγ8-containing AMPA receptors were enriched in the hippocampus and cerebral cortex, and expression was
minimal in the cerebellum and brain stem • Cohort 1 (Phase 2a focal epilepsy trial dosing regimen) exceeded the target RO range associated with maximal efficacy in preclinical models (50%-70%) while maintaining tolerability •
Collectively, PET and MAD-2 trials demonstrated that target plasma concentrations and associated RO could be achieved within 5 days Note: Results are based on preliminary analysis of the data. Clinical conduct of the PET and MAD-2 trials is
complete, and the clinical study reports for both are in progress. 20

RAP-219 Phase 1: SAD vs. MAD exposures * * * *Pending finalization
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RAP-219 Phase 1: MAD-1 trial results At highest dose, no TEAEs above
Grade 1 and no treatment-related TEAEs Dose in Phase 2a focal epilepsy trial 1 Possibly related or probably related 22

Potentially optimal target profile emerging for RAP-219 in focal
epilepsy Ideal Product Profile RAP-219 Emerging Profile Reduces seizures potently At low dose, reduced seizures in validated preclinical without evidence of sedation epilepsy models Displays no dose limiting Highest dose evaluated was considered to
be generally toxicities well tolerated Potential for reduced Low DDI potential as RAP-219 not observed to interact drug-drug interactions with CYP enzymes No treatment related TEAEs above Grade 2 in Phase 1 Generally well tolerated trials; no
sedation or motoric impairments Potential for greater Target RO achieved and exceeded while maintaining therapeutic index differentiated tolerability profile Convenient administration QD, single step-up dosing 23

RAP-219 overview A. Mechanism of action and preclinical development B.
Phase 1 trials C. Phase 2a proof-of-concept trial in refractory focal epilepsy D. Bipolar mania and diabetic peripheral neuropathic pain 24

Phase 2a proof-of-concept trial in refractory focal epilepsy Key design
considerations • Same patient population to be used in registrational trials – refractory FOS patients • Informs dose selection and effect size • Utilizes a recognized seizure biomarker demonstrated to predict clinical
response • Enables rapid progression into registrational trials 25

RAP-219 Phase 2a PoC trial in refractory focal epilepsy iEEG-recorded
clinical seizure biomarker used to evaluate efficacy RNS System Principal investigator Jacqueline French, M.D. • FDA-approved implantable device continually Professor, Neurology monitors and records seizure activity (intracranial NYU Grossman
School of Medicine EEG) in patients with FOS 1 • RNS system patients (>6,500 patients in the U.S. ) are demographically similar to those enrolled in a Trial overview 2 third-party registrational FOS study (duration of • Multi-center
open-label trial epilepsy, # of seizures, # of ASMs) • Approximately 20 adult drug-resistant focal epilepsy patients • MAD-1 Cohort 5/PET Cohort 1 dose: 0.75 mg/day for 5 days followed by 1.25 mg/day Phase 2a trial ongoing; topline
results expected in Q3 2025 1 Source: NeuroPace, January 2025 2 Based on a comparison of NeuroPace’s long-term treatment retrospective study and a Phase 2 trial example published in 2020. Example Phase 2 trial patient demographic information
does not include patients with the RNS system implanted, nor purport to reflect the actual or potential patient demographics of any of the Company’s Phase 1 clinical trials or any planned Phase 2 clinical trials. 26

RAP-219 Phase 2a PoC trial schema in refractory focal epilepsy 4-week
8-week open-label 8-week pre-treatment period treatment period follow-up period Eligibility criteria review 28-day Including review of 8 weeks of RAP-219 washout retrospective RNS system data prospective RAP-219 treatment period RNS data collection,
ongoing clinical seizure diary collection baseline period [estimated time: 1-2 weeks] 1. Confirm localization of seizure 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 onset zone and electrode placement Start of End of End of Start of 2. Confirm
stability of RNS system Treatment Treatment Trial Enrollment settings and therapies Establish baseline Evaluate the effect of RAP-219 on long Follow-up to allow for washout and 3. Provide historical iEEG data iEEG and clinical episodes and other
iEEG biomarkers potential return to baseline iEEG with at least an average of 8 seizure frequency and biomarker event frequency (RNS measures and evaluate PK/PD LEs per 4-week interval measured long episodes) as well as relationship 4. At least 1
clinical seizure during establish PK/PD relationship 8-week retrospective period Key endpoints: • Change in LE frequency on treatment compared to baseline • LE frequency responder analysis (% of patients that demonstrate ≥30%
reduction in LEs) • Change in estimated electrographic seizure frequency, CS frequency, and additional iEEG biomarkers • Clinically meaningful improvements in global ratings (PGIC/CGIC) 27

Focal epilepsy PoC model comparison Photosensitivity Transcranial
Magnetic Stimulation Ideal Model RNS (PPR) (TMS) Uses focal epilepsy Yes No No patient population Long episode reduction Generalized Recognized seizure TMS-evoked EEG shown to predict clinical photoparoxysmal EEG biomarker potentials (TEPs) seizure
reduction responses Measures drug effect on Measures evoked Measures provoked Obtains data on FOS biomarker of focal generalized epileptiform cortical hyperexcitability in effect size onset seizure discharges normal healthy volunteers PK/PD data
will allow Indirect dose response Indirect dose response Informs dose selection direct measure of degree readout for non-FOS readout of cortical for registrational trials of efficacy at different seizure hyperexcitability in HNV exposure levels
Expect translatable data Enables rapid Does not provide dosing or Does not provide dosing or that can inform dose and progression into effect size for FOS effect size for FOS effect size for future registrational trial registration trials
registration trials registrational trials Source: Porter et al. (2016); Biondi et al. (2022) 28

Long episodes (LEs) Objective and translatable biomarker for clinical
seizure frequency Change in seizure activity recorded through intracranial EEG (iEEG) 2 1 predicted ASM clinical response • RNS detects a biomarker of clinical seizures – long episodes (LEs), which are considered subclinical seizures
• LEs are runs of ictal or interictal epileptiform activity exceeding a specified duration (typically 30 “Long episode rates had the strongest correlation with seconds) “It could be argued that long changes in clinical seizure
• LEs avoid common seizure diary episodes are an even better rates. These data suggest that challenges -- memory impairments, therapeutic target than these measures may provide reported clinical seizures.” nocturnal or amnesic seizures,
and an objective assessment of cortical excitability and inaccurate reporting response to AEDs.” • All Phase 2a FOS study patients must have a high correlation between their LEs and electrographic seizures 1 The RNS system is also a
therapeutic device for adults with drug-resistant focal epilepsy 2 29 Epilepsy & Behavior. 2018; 83: 192-200; Epilepsia. 2020; 61:138-148.

Optimal cut point for reduction in LE frequency to predict meaningful
change in CS frequency • A 30% reduction in LEs was associated with a 50% or greater reduction in CS in a post-hoc analysis, regardless of the antiseizure medication initiated • High positive predictive value -- LEs correlate with
patient diary-reported seizures and CS are always associated with the presence of LEs • High negative predictive value -- the absence of a LE indicates that no epileptic seizure occurred LE & CS exhibit linear relationship (i.e. move in A
≥30% reduction in LE frequency correlates the same direction) with a ≥50% reduction in CS Percentage of LE Frequency Reduction by CS Responder Group Clinical Seizure Reduction & Correlated LE Frequency Reduction CS Reduction cut
Positive Sensitivity Specificity frequency AUC point in LE predictive (%) (%) a reduction frequency (%) ability LE & CS exhibit linear relationship (i.e. move in the same direction) >25% 0.725 25.6 64.3 64.7 64.4 b >50% 0.765 30.0 69.6
68.2 68.9 c >75% 0.735 49.6 63.6 64.7 64.4 Source: Gammaitoni et al, American Epilepsy Society (AES) 2024 Annual Meeting, Poster #1.494 30

RAP-219 overview A. Mechanism of action and preclinical development B.
Phase 1 SAD/MAD trials C. Phase 2a proof-of-concept trial in refractory focal epilepsy D. Bipolar mania and diabetic peripheral neuropathic pain 31

Bipolar mania Strong mechanistic data for RAP-219 Bipolar disorder
Rationale for RAP-219 • Diagnosed prevalence is ~2.8 percent of the • Bipolar disorder is associated with hyperactivity adult population in the U.S. (~7 million adults) in the hippocampus, where TARPγ8 is enriched • Bipolar
risk alleles overrepresented in genes • Condition is characterized extreme shifts in encoding synaptic signaling proteins with high mood, referred to as “manic-depressive” specificity of expression in neurons of the • Bipolar
mania is characterized by feelings of prefrontal cortex and hippocampus over-excitement, irritability, impulsivity, grandiose • Other ASMs (such as valproate, lamotrigine, and beliefs and racing thoughts carbamazepine) are FDA approved to
treat • Typically treated with antipsychotic medications bipolar disorder as either monotherapy or in combination therapy • The corneal kindling model of epilepsy is with mood stabilizers believed by some experts to be predictive of
bipolar treatments • Drug treatments often poorly tolerated with safety risks Phase 2a trial in bipolar mania expected to be initiated in Q3 2025; topline results expected 1H 2027 32

Diabetic peripheral neuropathic pain Strong mechanistic and compelling
preclinical data for RAP-219 RTX-1738 (TARPγ8 NAM/RAP-219 analog) attenuates 1 • Diagnosed U.S. prevalence: ~5.6 million tactile allodynia in spinal nerve ligation (SNL) rat model • Incl. diabetic peripheral neuropathic pain,
postherpetic • Starting on Day 16 (third day of dosing) and continuing neuralgia, trigeminal neuralgia, and idiopathic sensory through Day 20, paw withdrawal thresholds were elevated, polyneuropathy reflecting decreased pain behavior •
Caused by injury or dysfunction of peripheral nerves • Significant unmet need for new drugs with: RTX-1738/RAP-219 analog (3 mg/kg) − Novel MOA Vehicle − Once per day dosing − Improved tolerability − Minimal or no
drug-drug interactions − No abuse or cardiovascular liabilities • TARPγ8 is expressed in the spinal cord dorsal horn, where the sensation of pain (nociception) enters the CNS, and the anterior cingulate cortex, where the affective
or emotional aspects of pain resides 1 Diagnosed prevalence across diabetic peripheral neuropathy (~2.8 million), *p<0.001 RTX-1738 vs. Vehicle group by two-way ANOVA followed by Dunnett‘s Multiple post-herpetic neuralgia (~1.8 million),
and trigeminal neuralgia (~1.0 million). Comparison Test (n=10) 33

nAChR discovery programs 34

α6 nAChR program Preclinically-validated approach to neuropathic
pain • nAChR agonists have been observed to be efficacious Chrna6 WT Chrna4 WT 150 in third-party preclinical and clinical neuropathic pain Chrna6 KO Chrna4 KO studies; preclinical evidence in acute, inflammatory, 125 and neuropathic pain 100
• Abbott’s pan-nAChR agonist demonstrated significant improvements in patients with diabetic neuropathic 75 pain, but up to 66% of patients withdrew from the trial due to AEs such as nausea, dizziness, vomiting, 50 abnormal dreams, and
asthenia 25 *** ** • Evidence shows that α6 is a potential target for chronic pain 0 Neuropathic (CCI) Inflammatory (CFA) Genetic knockout (KO) mice demonstrate requirement of α6- but not α4-containing nicotinic receptors for
anti-allodynia mediated by intrathecal nicotine administration www.ScienceTranslationalMedicine.org 13 May 2015 Vol 7 Issue 287 287ra72 35 % Anti-allodynia

α9α10 nAChR program Potential for first-in-class approach to
hearing disorders • Potential for α9α10 nAChRs in hearing disorders demonstrated in preclinical studies • Engagement of α9α10 has been observed to mitigate hearing loss in preclinical models • Our RAP platform
technology enabled Rapport to identify potentially first-in- class orally-delivered agonists that • (Left) Auditory brainstem responses (ABRs) are elevated at 1 are selective for α9α10 nAChRs day but not at 7 days following acoustic
trauma (AT) • (Middle) α9 KO elevates ABR thresholds at 1 and 7 days after acoustic trauma • (Right) α9 gain of function knock-in (L9’T KI) completely prevents acoustic trauma hearing deficits PNAS 2020 117: 11811-9
36

Rapport Therapeutics: Charting new paths in neuroscience with
groundbreaking precision Experienced leadership Lead asset in clinical development for the treatment of refractory focal epilepsy Proven track record of building companies, novel therapies, and development platforms Data demonstrate RAP-219’s
potential to deliver transformative outcomes for patients Proprietary program Therapeutic potential across multiple indications Pioneered discoveries of RAPs IP expiration in 2036 + potential PTE Significant markets, including focal epilepsy,
peripheral neuropathic pain, and bipolar disorder Neuroanatomical specificity Steady cadence of milestones anticipated Technology designed to create precisely targeted neuromedicines, potentially overcoming limitations Robust clinical and discovery
pipeline with multiple of conventional treatments anticipated upcoming milestones 37

Thank you
Exhibit 99.2
Rapport Therapeutics Announces Appointment of Dr. Jeffrey Sevigny as Chief Medical Officer to Drive
Clinical Strategy and Precision Medicine Development
BOSTON and SAN DIEGO, March 3, 2025 Rapport Therapeutics, Inc. (Nasdaq: RAPP), a
clinical-stage biotechnology company dedicated to the discovery and development of small molecule precision medicines for patients suffering from central nervous system (CNS) disorders, today announced the appointment of Dr. Jeffrey Sevigny as
chief medical officer (CMO), effective immediately. A physician-scientist with more than 15 years of leadership in translational and clinical drug development, Dr. Sevigny has spearheaded groundbreaking research across neuroscience and rare
diseases. His experience spans the full spectrum of development, from discovery to late-stage clinical trials and regulatory approvals, and with a strong record of portfolio development and building high-performing organizations, he brings deep
strategic and operational experience to Rapport.
Dr. Sevigny joins Rapport following his tenure as chief medical officer at Prevail Therapeutics, a
wholly owned subsidiary of Eli Lilly, and senior vice president of Neuroscience at Eli Lilly. While at Prevail, Dr. Sevigny built and led the companys clinical development organization, while playing a pivotal role in the companys
corporate success, including rounds of financing, an IPO, and an acquisition by Eli Lilly. His career has been marked by strong leadership in major pharmaceutical and biotech companies, where he has led highly effective translational and clinical
development organizations, collaborative and successful interactions with regulatory authorities, and pioneering initiatives in neuroscience and other therapeutic areas.
In his role as CMO, Dr. Sevigny will oversee the development and execution of Rapports clinical strategy and will be responsible for ensuring the
advancement of Rapports pipeline of precision medicines leveraging receptor associated protein (RAP) science. Building on the momentum of Rapports RAP-219 program, his proven ability to advance
clinical programs through late-stage clinical trials and regulatory approval will be instrumental in progressing RAP-219 and the broader pipeline.
We are thrilled to welcome Jeff to Rapport. His extensive experience leading successful clinical development programs and driving drug development in
neuroscience make him the ideal addition to our executive team and leader of our clinical development capability, said Abraham N. Ceesay, chief executive officer of Rapport. Jeffs proven ability in building effective teams,
collaborating with regulatory authorities, and partnering with patient advocacy organizations to advance novel therapies will be invaluable as we continue advance our mission of bringing transformational treatments to patients living with
neurological disorders worldwide.
Throughout his career, Dr. Sevigny has held pivotal leadership roles at global pharmaceutical and
biotech companies, including F. Hoffmann-La Roche, Biogen, Novartis, and Merck, where he contributed to significant advancements in neuroscience research and development. Beyond his industry roles,
Dr. Sevigny has held academic appointments as assistant professor of Neurology at Albert Einstein School of Medicine and assistant professor of Clinical Neurology at Columbia University.
I am honored to join Rapport and work with this exceptional team to lead a new era of precision neuroscience, said Dr. Sevigny.
Rapports deep scientific foundation, compelling Phase 1 data from the RAP-219 program, and portfolio of potential clinical candidates set it apart from the field. With RAP-219 progressing through clinical development and key milestones on the horizon, I am eager to help bring this and other potentially transformative medicines to patients in need of better treatment options.
About Rapport Therapeutics
Rapport Therapeutics is
a clinical-stage biotechnology company dedicated to discovering and developing small molecule precision medicines for patients suffering from central nervous system (CNS) disorders. The Companys founders have made pioneering discoveries
related to the function of receptor associated proteins (RAPs) in the brain. Their findings form the basis of Rapports RAP technology platform, which enables a differentiated approach to generate precision small molecule product candidates
with the potential to overcome many limitations of conventional neurology drug discovery. Rapports precision neuroscience pipeline includes the Companys lead clinical program, RAP-219, designed to
achieve neuroanatomical specificity through its selective targeting of a RAP expressed in only discrete regions of the brain. The Company is currently advancing RAP-219 in clinical trials in focal epilepsy,
diabetic peripheral neuropathic pain, and bipolar mania. Additional preclinical and late-stage discovery stage programs are also underway, targeting CNS disorders including chronic pain and hearing disorders.
Forward-Looking Statements
This press release 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,
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; the ability of RAP-219 and other products in Rapports pipeline to deliver transformative
outcomes for patients; and Rapports RAP technology
platform. Forward looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect Rapports 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 companys research and development activities, including that interim,
topline and preliminary data from our clinical trials that we announce or publish from time to time are subject to audit and verification procedures that could result in material changes in the final data; Rapports 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 companys dependence on third parties to conduct clinical
trials, manufacture its product candidates and develop and commercialize its product candidates, if approved; Rapports ability to attract, integrate and retain key personnel; risks related to the companys 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 Rapports intellectual property protections; and risks related to the competitive landscape for Rapports product candidates; as well as other risks described in
Risk Factors, in the companys Registration Statement on Form S-1, and most recent Quarterly Report on Form 10-Q, as well as discussions of potential
risks, uncertainties, and other important factors in Rapports subsequent filings with the Securities and Exchange Commission. 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.
Contact:
Julie DiCarlo
Head of Communications & IR
Rapport Therapeutics
jdicarlo@rapportrx.com
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