# EDGAR Filing Document

**Accession Number:** 0002012593
**File Stem:** 0000950170-25-080247
**Filing Date:** 2025-6
**Character Count:** 57850
**Document Hash:** c48828a8dfb31743056600eed9b07df6
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0000950170-25-080247.hdr.sgml**: 20250602

**ACCESSION NUMBER**: 0000950170-25-080247

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 59

**CONFORMED PERIOD OF REPORT**: 20250602

**ITEM INFORMATION**: Regulation FD Disclosure

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20250602

**DATE AS OF CHANGE**: 20250602

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** Rapport Therapeutics, Inc.
- **CENTRAL INDEX KEY:** 0002012593
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 880724208
- **STATE OF INCORPORATION:** DE
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-42121
- **FILM NUMBER:** 251014982

**BUSINESS ADDRESS:**
- **STREET 1:** 1325 BOYLSTON STREET
- **STREET 2:** SUITE 401
- **CITY:** BOSTON
- **STATE:** MA
- **ZIP:** 02215
- **BUSINESS PHONE:** 857-321-8020

**MAIL ADDRESS:**
- **STREET 1:** 1325 BOYLSTON STREET
- **STREET 2:** SUITE 401
- **CITY:** BOSTON
- **STATE:** MA
- **ZIP:** 02215

?xml version='1.0' encoding='ASCII'? 8-K

**UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549**

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## **FORM** 8-K

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**CURRENT REPORT**

**Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934**

**Date of Report (Date of earliest event reported):** June 02, 2025<br>

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Rapport Therapeutics, Inc.

**(Exact name of Registrant as Specified in Its Charter)**

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| | | |
|:---|:---|:---|
| Delaware | 001-42121 | 88-0724208 |
| **(State or Other Jurisdiction<br>of Incorporation)** | **(Commission File Number)** | **(IRS Employer<br>Identification No.)** |
| 99 High Street<br>Suite 2100 |  |  |
| Boston**,** Massachusetts |  | 02110 |
| **(Address of Principal Executive Offices)** |  | **(Zip Code)** |

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**Registrant's Telephone Number, Including Area Code:** (857) 321-8020<br>

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| |
|:---|
| 1325 Boylston Street <br>Suite 401 |
| Boston**,** Massachusetts 02115 |

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**(Former Name or Former Address, if Changed Since Last Report)**

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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:

☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐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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| | | |
|:---|:---|:---|
| **<br>Title of each class** | **Trading<br>Symbol(s)** | **<br>Name of each exchange on which registered** |
| Common Stock, $0.001 par value per share  | RAPP | The Nasdaq Global Market |

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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. ☐

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| | |
|:---|:---|
| **Item 7.01** | **Regulation FD Disclosure.** |

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On June 2, 2025, Rapport Therapeutics, Inc. (the "Company" or "Rapport") furnished its corporate presentation, attached as Exhibit 99.1 to this Current Report on Form 8-K in connection with the Company's 2025 Investor and Analyst Day on June 2, 2025. The corporate presentation will also be available in the investor relations section of the Company's website at www.rapportrx.com.

Also on June 2, 2025 in connection with the 2025 Investor and Analyst Day, the Company issued a press release providing certain corporate updates. 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.*

## **Item 8.01 Other Events.** 
On June 2, 2025, the Company announced that its Phase 2a trial of RAP-219 in refractory focal epilepsy is fully enrolled and on track for topline results in September 2025.

In addition, the Company's update included data from the three completed Phase 1 multiple dose trials, including the multiple ascending dose human positron emission tomography (PET) trial from which final data were not available at the time of the Company's January disclosure. Final aggregate data (n=64) across the multiple dose trails continue to reinforce RAP-219's differentiated tolerability:

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•All treatment-emergent adverse events ("TEAEs") were Grade 1 or 2

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•No serious adverse events, nor clinically significant laboratory, vital signs, or electrocardiogram abnormalities

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•TEAEs occurred early in dosing and resolved without further action

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•Most common TEAEs: headache (n=12), dry mouth (n=5), brain fog (n=5), and fatigue (n=5)

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•Three discontinuations

***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, bipolar mania and diabetic peripheral neuropathic pain, including the initiation, timing, progress and results of our ongoing and planned clinical trials; expectations for the activity, tolerability, and commercial potential of RAP-219; the potential of Rapport's RAP technology platform.

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 the Company'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; the Company'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 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 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 the Company's Annual Report on Form 10-K, 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. Any forward-looking statements represent Rapport's views only as of today and should not be relied upon as representing its views as of any subsequent date. 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.

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## **Item 9.01 Financial Statements and Exhibits.** 
(d) Exhibits

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| | |
|:---|:---|
| 99.1 | [<u>Rapport Therapeutics, Inc. 2025 Investor & Analyst Day Presentation, furnished hereto</u>](rapp-ex99_1.htm) |
| 99.2 | [<u>Press Release dated June 2, 2025, furnished hereto</u>](rapp-ex99_2.htm) |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) |

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**SIGNATURES**

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. |
| Date: | June 2, 2025 | By:  | /s/ Troy Ignelzi |
|  |  |  | Troy Ignelzi<br>Chief Financial Officer |

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## Exhibit 99.1

![Slide 1](rapp-ex99_1s1.jpg)

Investor & Analyst Day June 2, 2025

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![Slide 2](rapp-ex99_1s2.jpg)

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 refractory focal epilepsy, bipolar mania and diabetic peripheral neuropathic pain, including the initiation, timing, progress and results of our ongoing and planned clinical trials; expectations for the activity, tolerability, and commercial potential of RAP-219; the potential of Rapport's RAP technology platform; 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 the company'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; the company'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 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 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 the company's Annual Report on Form 10-K 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. Any forward-looking statements represent Rapport's views only as of today and should not be relied upon as representing its views as of any subsequent date. 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.

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![Slide 3](rapp-ex99_1s3.jpg)

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 Perspective Jacqueline French, M.D., Professor of Neurology, NYU Langone \| Jeff Sevigny, M.D. 05 RAP-219: Phase 2a FOS Trial: Framing Future Data William Motley, M.D., RAP-219 Program Leader 06 Financial Update Troy Ignelzi, Chief Financial Officer 07 Questions and Answers 08 Closing Remarks Abe Ceesay

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![Slide 4](rapp-ex99_1s4.jpg)

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 Perspective Jacqueline French, M.D., Professor of Neurology, NYU Langone \| Jeff Sevigny, M.D. 05 RAP-219: Phase 2a FOS Trial: Framing Future Data William Motley, M.D., RAP-219 Program Leader 06 Financial Update Troy Ignelzi, Chief Financial Officer 07 Questions and Answers 08 Closing Remarks Abe Ceesay Agenda

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![Slide 5](rapp-ex99_1s5.jpg)

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 Steve Paul, M.D. Founder and Board ChairPartner, Third Rock Ventures John Maraganore, Ph.D. Director Former Founding CEO, Alnylam 1 Employee director. Robert Perez Director Operating Partner, General Atlantic, Former CEO, Cubist Pharmaceuticals Founder and Chairman, Life Science Cares Raymond Sanchez, M.D. Director Senior Advisor, Bain Life Sciences; Former CMO, Cerevel Therapeutics Paul Silva Director Former Chief Accounting Officer, Vertex Pharmaceuticals Management Team Board of Directors

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![Slide 6](rapp-ex99_1s6.jpg)

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 molecule precision medicines for patients with neurological and psychiatric disorders TARP8: transmembrane AMPA regulatory protein gamma-8; AMPAR: α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. 1 Includes cash, cash equivalents, and short-term investments, excluding restricted cash. Robust Clinical & Discovery Pipeline Potential first-in-class programs leveraging receptor associated protein (RAP) science RAP-219 forebrain restricted TARP8 AMPAR modulator–significant opportunity in initial indication in focal epilepsy Medicinal chemistry-enabled discovery portfolio with potential in additional indications Topline Phase 2a Results in refractory focal epilepsy expected in Q3 25 Initiate Phase 2a in bipolar mania in Q3 25 with topline results in 1H 27 Finalizing plans for Phase 2a in diabetic peripheral neuropathic pain RAP-219: Pipeline-in-a-Product with Multiple Catalysts Well Financed $285.4 million as ofMarch 31, 20251 Cash runway expected to fund operations through end of 2026

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![Slide 7](rapp-ex99_1s7.jpg)

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 noncompliance and discontinuation Drug discovery with conventional approaches (lacking RAPs) can miss high potential, previously unexplored targets 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 designed for increased selectivity, providing neuroanatomical specificity RAPs can enable differentiated pharmacology and potentially provide favorable efficacy, safety, and administration profiles RAPs can "unlock" drug targets previously inaccessible to study in vitro, allowing for potentially first-in-class drug discovery programs Conventional CNS drug discovery The potential of RAPs

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![Slide 8](rapp-ex99_1s8.jpg)

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 Phase 1 Phase 2 Phase 3 Next Expected Milestone RAP-219 TARPγ8 AMPAR Programs Refractory Focal Epilepsy Topline Results September 2025 AMPA modulator Bipolar Mania Trial Initiation Q3 2025 Topline Results 1H 2027 Diabetic Peripheral Neuropathic Pain Trial Initiation1 nAChR2 Discovery Programs α6 Chronic Pain Development Candidate α9α10 Hearing Disorders Development Candidate Strong intellectual property with worldwide rights to all programs Trial Underway; Enrollment Complete

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![Slide 9](rapp-ex99_1s9.jpg)

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); trigeminal neuralgia (~1.0 million). Potency data and metabolic profile support RAP-219's development as a long acting injectable, which could improve compliance and outcomes Focal epilepsy in U.S. patients1 Peripheral neuropathic pain in U.S. patients3 Bipolar disorder in U.S. patients2 ~1.8M ~7.2M ~5.6M TARP8 is a preclinically and clinically validated target for epilepsy Once daily (QD) dosing Differentiated tolerability profile No observed drug-drug interactions (DDI) Compelling data supporting potential in bipolar disorder and peripheral neuropathic pain

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![Slide 10](rapp-ex99_1s10.jpg)

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 (ages 18+) 60% Focal Epilepsy 1.8M Focal Epilepsy Patients 30-40% % Drug-resistant1 Limited Efficacy: Despite over 20 FDA approved ASMs, 30-40% of patients are still drug-resistant1 Tolerability Issues: Especially CNS side-effects, such as sedation, ataxia, and cognitive problems Potential for Serious Adverse Events: Such as severe cutaneous reactions, serious hematological disorders, and hepatic failure Risk of Breakthrough Seizures: Missing doses of seizure medicine is the most common cause of breakthrough seizures due to the short half-life of many antiseizure medications2 Complicated Administration: Long titration, drug-drug interactions, and lab monitoring

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![Slide 11](rapp-ex99_1s11.jpg)

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 Perspective Jacqueline French, M.D., Professor of Neurology, NYU Langone \| Jeff Sevigny, M.D. 05 RAP-219: Phase 2a FOS Trial: Framing Future Data William Motley, M.D., RAP-219 Program Leader 06 Financial Update Troy Ignelzi, Chief Financial Officer 07 Questions and Answers 08 Closing Remarks Abe Ceesay Agenda

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![Slide 12](rapp-ex99_1s12.jpg)

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 onset seizures do not originate in hindbrain structures AMPA type glutamate receptors at excitatory synapses can mediate seizure initiation and spread AMPAR target is clinically validated - perampanel (FYCOMPA®) is an FDA/EMA approved pan-AMPAR antagonist for the treatment of focal onset and generalized seizures AMPA receptors (AMPAR) in epilepsy Mesial temporal lobe and cerebral cortex are the keybrain areas associated with focal onset seizures Pre-synaptic neuron Post-synaptic neuron Na+ channel Action potential glutamate Ca2+ channel AMPAR Na+ Transmitter release Ca2+ Na+ perampanel EPSP K+ channel Depolarization Na+ Amygdala Cerebral cortex Brainstem Hippocampus Cerebellum

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![Slide 13](rapp-ex99_1s13.jpg)

NatComm 2022 13:734 GluA1 GluA2 TARP8 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 High expression in the neocortex and mesial temporal lobe, where nearly all seizures originate Relatively low expression in cerebellum, thalamus and brainstem Cryogenic electron microscopy of GluA1/2 + TARPγ8 complex

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![Slide 14](rapp-ex99_1s14.jpg)

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/CYP inhibition/CYP induction >10,000 X target affinity. Not CYP substrate Solubility/permeability BCS Class I Target receptor occupancy 50% RO at <50 μg/kg oral dose in rodent Preclinical safety NOAEL in top dose of IND enabling studies Non-sedating No effects at exposures 1000X EC50 NMDAR: N-methyl-D-aspartate receptor; DDI: drug-drug interactions; BCS: Biopharmaceutics Classification System; NOAEL: No Observed Adverse Effect Level.

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![Slide 15](rapp-ex99_1s15.jpg)

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 (%) % Corneal Kindling Responders

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![Slide 16](rapp-ex99_1s16.jpg)

% 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 gold standard assay for assessing motor coordination and detecting common ASM side effects like sedation, somnolence, and ataxia

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![Slide 17](rapp-ex99_1s17.jpg)

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 studies at different points in time, with differences in preclinical study design and subject population. As a result, cross-study comparisons cannot be made. No head-to-head studies have been conducted. RAP-2191 Levetiracetam Tiagabine Ezogabine Carbamazepine Valproate Lacosamide Clobazam Gabapentin Lamotrigine Topiramate Phenytoin Corneal kindling mouse model therapeutic index (TD50 rotarod/ED50 efficacy) for RAP-2191 and other ASMs2

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![Slide 18](rapp-ex99_1s18.jpg)

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 seizure models Activity not seen in maximal electroshock (MES) model, consistent with performance of levetiracetam and some other effective ASMs Potent activity in kindling model has been observed to predict efficacy in focal epilepsy \* Used RAP-219; where not noted, used other TARPg8 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. Chronic seizure models [like corneal kindling] offer the most etiologically relevant platform on which to accurately replicate clinical epilepsy" Barker-Haliski, Expert Opinion on Drug Discovery Model Corneal kindling – mouse\* PTZ - mouse\* Rotarod\* Amygdala kindling – mouse Hippocampal kindling – mouse 6Hz stimulation – mouse Frings audiogenic seizure – mouse GAERS absence epilepsy – rat

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![Slide 19](rapp-ex99_1s19.jpg)

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 Perspective Jacqueline French, M.D., Professor of Neurology, NYU Langone \| Jeff Sevigny, M.D. 05 RAP-219: Phase 2a FOS Trial: Framing Future Data William Motley, M.D., RAP-219 Program Leader 06 Financial Update Troy Ignelzi, Chief Financial Officer 07 Questions and Answers 08 Closing Remarks Abe Ceesay Agenda

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![Slide 20](rapp-ex99_1s20.jpg)

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 Food Effect N=16\* 0.25 mg x 7d 0.5 mg x 7d 0.25 mg x 14d 0.75 mg x 5d 1.25 mg x 9d N=18\* 0.5 mg x 2d 1.0 mg x 2d 1.75 mg x 24d 0.75 mg x 2d 1.25 mg x 2d 1.75 mg x 4d 0.75 mg x 3d 1.25 mg x 3d 1.75 mg x 2d N=30\* 0.75 mg x 5d 1.25 mg x 23d 0.75 mg x 28d 0.5 mg x 28d 0.25 mg x 7d 0.5 mg x 7d 0.25 mg x 14d \* Number of subjects receiving RAP-219. SAD: Single ascending dose; MAD: Multiple ascending dose; PET: Positron emission tomography.

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![Slide 21](rapp-ex99_1s21.jpg)

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 volunteers Note: Includes studies 102, 103, 104; AE start date is after first dose of RAP-219. TEAE: Treatment emergent adverse event; SAE: Serious adverse event; ECG: Electrocardiogram. TEAEs (≥ 5% participants) Total(N=64) n (%) n grade 1/2 Placebo(N=16)n (%) Headache 12 (18.75%) 9/3 0 Dry mouth 5 (7.81%) 4/1 0 Brain fog 5 (7.81%) 5/0 1 (6.25%) Fatigue 5 (7.81%) 5/0 0 Sinus tachycardia 4 (6.25%) 4/0 0 Insomnia 4 (6.25%) 4/0 0 Decreased appetite 4 (6.25%) 4/0 1 (6.25%) Diarrhea 4 (6.25%) 4/0 0 Vision blurred 4 (6.25%) 3/1 0 Medical device site reaction 3 (4.69%) 0/3 1 (6.25%) Constipation 3 (4.69%) 3/0 1 (6.25%) Disturbance in attention 3 (4.69%) 3/0 0 Catheter site hematoma 3 (4.69%) 2/1 0 Back pain 3 (4.69%) 3/0 0 Abnormal dreams 3 (4.69%) 3/0 0 Bowel movement irregularity 3 (4.69%) 2/1 0

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![Slide 22](rapp-ex99_1s22.jpg)

RAP-219 human PET study TARP8 highly expressed in neocortex and mesial temporal lobe High expression of TARP8 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 brainstem supports a potentially favorable and differentiated benefit/risk profile Group-averaged parametric PET images (co-registered to MRI) following tracer administration in 16 subjects. Low expression

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![Slide 23](rapp-ex99_1s23.jpg)

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 (as low as 0.25 mg), and lower than the dose being used in Phase 2a FOS trial, potentially affording greater flexibility in dose selection Phase 2a dose (green line) achieves target RO within 5 days and > 80% RO by day 28 Simulated RO based on Phase 1 PK and PET RO data RO: Receptor occupancy. \*Trough values calculated based on non-parametric superposition using data from the 101 and 102 studies 85% RO 80% RO 70% RO 60% RO 50% RO RAP-219 Trough\* Concentration (ng/mL) 0.75 mg x 5 days, 1.25 mg/day x 23 days 0.75 mg x 28 days 0.25 mg x 28 days

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![Slide 24](rapp-ex99_1s24.jpg)

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 originate PET results confirm TARP8 expressed in neocortex and mesial temporal lobe with relatively low expression in cerebellum, thalamus, and brainstem Doses as low as 0.25 mg predicted to achieve clinically efficacious exposures, based on human dose-exposure-RO PET results May afford flexibility in dosing to optimize tolerability and potential benefit Excellent pharmaceutical properties supporting development Once-a-day dosing; minimal or no DDIs; no CYP interactions observed CYP: Cytochrome P450.

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![Slide 25](rapp-ex99_1s25.jpg)

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 Perspective Jacqueline French, M.D., Professor of Neurology, NYU Langone \| Jeff Sevigny, M.D. 05 RAP-219: Phase 2a FOS Trial: Framing Future Data William Motley, M.D., RAP-219 Program Leader 06 Financial Update Troy Ignelzi, Chief Financial Officer 07 Questions and Answers 08 Closing Remarks Abe Ceesay Agenda

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![Slide 26](rapp-ex99_1s26.jpg)

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 FDA-approved device for patients with refractory FOS Approx. 6,500 RNS-treated patients in the U.S.1 1 Source: NeuroPace, January 2025 Neuropace RNS System®

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![Slide 27](rapp-ex99_1s27.jpg)

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 Epileptiformdischarges Clinical Seizures Long Episodes / Electrographic Seizures Episode Starts

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![Slide 28](rapp-ex99_1s28.jpg)

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 long episode rates had the strongest correlation with changes in clinical seizure rates. These data suggest that these measures may provide an objective assessment of cortical excitability and response to AEDs."

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![Slide 29](rapp-ex99_1s29.jpg)

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, Poster #1.494. Skarpaas (2018)1: significant correlation exists between reduction in long episodes and clinical seizure frequency Quraishi (2020)2: ASMs resulting in a ≥ 20% decrease in long episodes were clinical efficacious (≥ 50% reduction in seizures) Gammaitoni (2024)3: ASMs resulting in a ≥ 30% reduction in LEs were associated with a ≥ 50% reduction in clinical seizures N=45 from three highly effective ASMs ASMs initiated: CLB (n=15), LEV (n=4), LCM (n=26)

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![Slide 30](rapp-ex99_1s30.jpg)

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 LEs during 8-week retrospective review period ≥ 1 clinical seizure reported during 8-week retrospective review period > 50% concordance between long episodes and electrographic seizures RAP-219 washout RNS data collection, ongoing clinical seizure diary collection 0.75 mg x 5 days then 1.25 mg Baseline (no treatment) 4-week pre-treatment period 8-week open-label treatment period 8-week follow-up period End of Treatment End of Trial Start of Treatment Start of Enrollment Key Endpoints Long episode reduction proportion of patients with ≥30% reduction compared with baseline\* median percent change from baseline Clinical seizure reduction proportion of patients with ≥50% reduction compared with pre-treatment baseline median percent change from baseline Percent change in estimated electrographic seizure frequency and additional iEEG biomarkers Key Entry Criteria \* Baseline defined as 4-week average number of LEs over 4-week pretreatment, the 4-week screening, and the 4–week retrospective review periods.

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![Slide 31](rapp-ex99_1s31.jpg)

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 unlocked and ongoing study database. Median (1st to 4th quartile range) CS frequency per 28 days in 4-week prospective baseline 10 (4.25-18.25) LE frequency per 28 days in 12-week baseline 51 (21-194) Concordance between LEs and electrographic seizures (rated by an independent reviewer) 92% (71-96) Concomitant antiseizure medications 3 Baseline Characteristics from First 14 Patients Enrolled Median (range) Age 37 (20-61) Sex (n) 7F/7M Age at first seizure 19 (0.5-31) Years since RNS implantation 4.4 (1.4-10.2)

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![Slide 32](rapp-ex99_1s32.jpg)

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 Perspective Jacqueline French, M.D., Professor of Neurology, NYU Langone \| Jeff Sevigny, M.D. 05 RAP-219: Phase 2a FOS Trial: Framing Future Data William Motley, M.D., RAP-219 Program Leader 06 Financial Update Troy Ignelzi, Chief Financial Officer 07 Questions and Answers 08 Closing Remarks Abe Ceesay

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![Slide 33](rapp-ex99_1s33.jpg)

Fireside Chat: KOL Perspective Jacqueline French, M.D. Professor of Neurology, NYU Langone Jeff Sevigny, M.D. Chief Medical Officer

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![Slide 34](rapp-ex99_1s34.jpg)

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 Perspective Jacqueline French, M.D., Professor of Neurology, NYU Langone \| Jeff Sevigny, M.D. 05 RAP-219: Phase 2a FOS Trial: Framing Future Data William Motley, M.D., RAP-219 Program Leader 06 Financial Update Troy Ignelzi, Chief Financial Officer 07 Questions and Answers 08 Closing Remarks Abe Ceesay Agenda

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![Slide 35](rapp-ex99_1s35.jpg)

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

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![Slide 36](rapp-ex99_1s36.jpg)

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 evidence of activity to support advancement to registrational trials As noted earlier, responder is defined by a ≥30% reduction in LE seizure frequency, consistent with a clinically meaningful effect Example highly effective medication starts of a marketed ASM\* Episode Starts Long Episodes Before medication start Titration Maintenance \*RNS data with introduction of currently marketed ASM; not RAP-219 data.

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![Slide 37](rapp-ex99_1s37.jpg)

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 changes Target responder rate set at ≥40% to align with clinical relevance and support advancement to pivotal trials Sources: Fig 1: (1) Chung et.al. Neurology 2020;94:e2311-e2322 (2) Krauss et.al. Lancet Neurol 2020;19:38-48, (3) French, et.al. XTOLE AES poster t we 1.419 December 2021, (4) (5) (6) Product package inserts. Non-Placebo Adjusted Proportion of 50% CS Responders in Registrational Trials of Approved and Pipeline Programs

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![Slide 38](rapp-ex99_1s38.jpg)

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 Clinical Seizure Key Secondary Endpoint Analysis Proportion of patients achieving ≥50% reduction in clinical seizures compared with baseline Median percent change in clinical seizure frequency compared with baseline TEAE Incidence and Grade \*Power determinations were based on this outcome measure.

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![Slide 39](rapp-ex99_1s39.jpg)

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 with baseline ~30% Clinical Seizure Key Secondary Endpoint Analysis Proportion of patients achieving ≥50% reduction in clinical seizures compared with baseline ≥40% Median percent change in clinical seizure frequency compared with baseline ~50% TEAE Incidence and Grade \*Power determinations were based on this outcome measure.

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![Slide 40](rapp-ex99_1s40.jpg)

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 Perspective Jacqueline French, M.D., Professor of Neurology, NYU Langone \| Jeff Sevigny, M.D. 05 RAP-219: Phase 2a FOS Trial: Framing Future Data William Motley, M.D., RAP-219 Program Leader 06 Financial Update Troy Ignelzi, Chief Financial Officer 07 Questions and Answers 08 Closing Remarks Abe Ceesay Agenda

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![Slide 41](rapp-ex99_1s41.jpg)

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 peripheral neuropathy (~2.8 million), post-herpetic neuralgia (~1.8 million), and trigeminal neuralgia (~1.0 million). Focal epilepsy in U.S. patients1 ~1.8M Market Size 4%

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![Slide 42](rapp-ex99_1s42.jpg)

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 trial in bipolar mania expected to begin 2025 Plan for POC trial in diabetic peripheral neuropathic pain finalized 1H 2027 RAP-219 Phase 2a trial in bipolar mania topline results expected

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![Slide 43](rapp-ex99_1s43.jpg)

Questions & Answers

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![Slide 44](rapp-ex99_1s44.jpg)

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 Perspective Jacqueline French, M.D., Professor of Neurology, NYU Langone \| Jeff Sevigny, M.D. 05 RAP-219: Phase 2a FOS Trial: Framing Future Data William Motley, M.D., RAP-219 Program Leader 06 Financial Update Troy Ignelzi– Chief Financial Officer 07 Questions and Answers 08 Closing Remarks Abe Ceesay

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![Slide 45](rapp-ex99_1s45.jpg)

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 improves probability of success for future pivotal trials Objective and translatable biomarker used as more reliable measure than patient-reported diaries Trial patients are representative of registration and commercial target patient population Majority of epilepsy opinion leaders believe design is superior to other proof-of-concept designs1 Validated across preclinical and Phase 1 studies Efficacy in highly predictive seizure models Potential to significantly improve therapeutic index Generally well tolerated across four Phase 1 trials with 100 subjects dosed (no TEAEs above Grade 2) Differentiated profile promotes broad potential use QD dosing and rapid achievement of target RO associated with maximal seizure protection Minimal drug-drug interactions and not observed to interact with CYP enzymes Long half life minimizes daily drug fluctuations and may reduce risk of breakthrough seizures Potency and physicochemical properties enable potential as first long-acting injectable ASM 1Third-party market research, March 2025

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![Slide 46](rapp-ex99_1s46.jpg)

Thank you

## Exhibit 99.2

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| | |
|:---|:---|
| ![img174368023_0.jpg](img174368023_0.jpg) | **&nbsp;&nbsp;&nbsp;&nbsp;Exhibit 99.2**  |

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**Rapport Therapeutics Hosts Investor and Analyst Day; Provides Corporate Updates**

*Phase 2a trial of RAP-219 in refractory focal epilepsy fully enrolled and on track for topline results in September 2025*

**BOSTON and SAN DIEGO, June 2, 2025** -- Rapport Therapeutics, Inc. (Nasdaq: RAPP) ("Rapport" or the "Company"), a clinical-stage biotechnology company dedicated to the discovery and development of small molecule precision medicines for patients with neurological or psychiatric disorders, today will host its inaugural Investor and Analyst Day, featuring presentations from Rapport's executive team on the Company's strategic priorities and updates from its clinical pipeline, including progress on the RAP-219 Phase 2a trial in focal epilepsy. The event's agenda also includes a fireside chat with key opinion leader and professor of Neurology at NYU Langone's Comprehensive Epilepsy Center, Jacqueline French, M.D., hosted by Rapport's Chief Medical Officer, Jeffrey Sevigny, M.D.

A livestream of the event and presentation materials will be available starting at 2:45 p.m. Eastern Time (ET) today and can be accessed by visiting 'News & Events' in the Investors section of the Company's website: https://investors.rapportrx.com.

"Our Phase 2a trial of RAP-219 in refractory focal epilepsy is now fully enrolled, and we remain on track to report topline results in September 2025," said Abraham N. Ceesay, Chief Executive Officer of Rapport Therapeutics. "This will mark a major milestone for our lead program and an opportunity to demonstrate the strength of our precision neuroscience approach. We're excited to share additional details about the trial ahead of the readout and honored to be joined by Dr. French, principal investigator of our RAP-219 epilepsy trial, who will provide valuable expert insight on the trial design and unmet need in focal epilepsy. Today's event allows us to further underscore the potential of RAP-219 as a differentiated therapeutic with broad clinical and commercial potential."

**Highlights of Rapport's Investor and Analyst Day event include the following:**

**<u>Phase 2a trial of RAP-219 in refractory focal epilepsy</u>**

The Phase 2a trial of RAP-219 in refractory focal epilepsy is now fully enrolled. This proof-of-concept trial, designed with input from leading epilepsy experts, uses intracranial electroencephalography (iEEG) data from the RNS System<sup></sup> to access RAP-219's potential effect on long episodes (LEs), an objective biomarker shown to correlate with clinical seizures (CSs).

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**Enrolled patients' baseline characteristics**

Preliminary baseline characteristics of the first 14 patients enrolled—those for whom baseline data are available—indicate that the trial population is representative of patients historically enrolled in registrational refractory focal epilepsy trials.

**<u>Baseline Characteristics of First 14 Patients Enrolled</u>**

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| | | | |
|:---|:---|:---|:---|
|  | &nbsp;&nbsp;**Median**<br>**(range)** |  | &nbsp;&nbsp;**Median**<br>**(1**<sup>st</sup> **to 4**<sup>th</sup> **quartile range)** |
| &nbsp;&nbsp;Age | &nbsp;&nbsp;37 (20-61) | &nbsp;&nbsp;CS frequency per 28 days in 4-week prospective baseline | &nbsp;&nbsp;10 (4.25-18.25) |
| &nbsp;&nbsp;Sex (n) | &nbsp;&nbsp;7F/7M | &nbsp;&nbsp;LE frequency per 28 days in 12-week baseline (8-week retrospective + 4-week prospective) | &nbsp;&nbsp;51 (21-194) |
| &nbsp;&nbsp;Age at first seizure | &nbsp;&nbsp;19 (0.5-31) | &nbsp;&nbsp;Concordance between LEs and electrographic seizure (rated by an independent reviewer) | &nbsp;&nbsp;92% (71-96) |
| &nbsp;&nbsp;Years since RNS implantation | &nbsp;&nbsp;4.4 (1.4-10.2) | &nbsp;&nbsp;Concomitant antiseizure medications | &nbsp;&nbsp;3 |

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**Anticipated analysis of Phase 2a topline data**

The Company expects to provide the following data analysis when topline results are reported in September 2025:

Primary endpoint analysis:

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•Proportion of patients achieving ≥30% reduction in LEs compared with 12-week baseline period

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•Median percent change in LE frequency compared with 12-week baseline period

Key secondary endpoint analysis:

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•Median percent change in CS frequency compared with 4-week prospective baseline

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•Proportion of patients achieving ≥50% reduction in CSs compared with 4-week prospective baseline

Treatment-emergent adverse event (TEAE) incidence and grade

**<u>RAP-219 Phase 1 development update</u>** 

**Consolidated Phase 1 safety summary** 

As disclosed in January, a total of four Phase 1 trials have been conducted—a single ascending dose trial, two multiple ascending dose trials, and a multiple ascending dose human positron emission tomography (PET) trial. Across these trials, 100 healthy volunteers have been exposed to RAP-219.

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The Company's update includes data from the three completed Phase 1 multiple dose trials, including the PET trial from which final data were not available at the time of the Company's January disclosure. Final aggregate data (n=64) across the multiple dose trails continue to reinforce RAP-219's differentiated tolerability:

oAll TEAEs were Grade 1 or 2

oNo serious adverse events (SAEs), nor clinically significant laboratory, vital signs, or electrocardiogram (ECG) abnormalities

oTEAEs occurred early in dosing and resolved without further action

oMost common TEAEs: headache (n=12), dry mouth (n=5), brain fog (n=5), and fatigue (n=5)

oThree discontinuations

**Upcoming catalysts** 

oSeptember 2025: RAP-219 Phase 2a topline readout in focal epilepsy

oQ3 2025: Initiation of RAP-219 Phase 2a trial in bipolar mania

o2H 2025: Update on the Company's diabetic peripheral neuropathic pain program

o1H 2027: RAP-219 Phase 2a topline readout in bipolar mania

**<u>Cash runway guidance</u>** 

As of March 31, 2025, Rapport reported $285.4 million in cash, cash equivalents, and short-term investments, excluding restricted cash. These funds are expected to support operations through the end of 2026.

**About RAP-219**

RAP-219 is a clinical-stage AMPA receptor (AMPAR) negative allosteric modulator (NAM) designed to achieve neuroanatomical specificity through its selective targeting of a receptor associated protein (RAP) known as TARPγ8, which is associated with neuronal AMPARs. Whereas AMPARs are distributed widely in the central nervous system, TARPγ8 is expressed only in discrete regions, including the hippocampus and neocortex, where focal seizures often originate. By contrast, TARPγ8 has minimal expression in the hindbrain, where drug effects are often associated with intolerable adverse events. With this precision approach, the Company believes RAP-219 has the potential to provide a differentiated profile as compared to traditional neuroscience medications. Due to the role of AMPA biology in various neurological disorders and the selective targeting of TARPγ8, the Company believes RAP-219 has pipeline-in-a-product potential and is evaluating the compound as a transformational treatment for patients with focal epilepsy, bipolar disorder, and peripheral neuropathic pain.

**Availability of Other Information About Rapport Therapeutics**

Rapport Therapeutics uses and intends to continue to use its Investor Relations website and LinkedIn (Rapport Therapeutics) as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company's Investor Relations website and LinkedIn, in addition to following the Company's press releases, SEC filings, public conference calls, presentations, and webcasts. The

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contents of the Company's website or social media shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended.

**About Rapport Therapeutics**

Rapport Therapeutics is a clinical-stage biotechnology company dedicated to discovering and developing small molecule precision medicines for patients with neurological or psychiatric disorders. The Company's founders have made pioneering discoveries related to the function of receptor associated proteins (RAPs) in the brain. Their findings form the basis of Rapport's 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. Rapport's precision neuroscience pipeline includes the Company's lead investigational drug, 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 pursuing RAP-219 as a potential treatment for refractory focal epilepsy, bipolar mania and diabetic peripheral neuropathic pain. Additional preclinical and late-stage discovery stage programs are also underway, including targeting 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 for the treatment of refractory focal epilepsy, bipolar mania and diabetic peripheral neuropathic pain, including the initiation, timing, progress and results of our ongoing and planned clinical trials; expectations for the activity, tolerability, and commercial potential of RAP-219; the potential of Rapport's RAP technology platform; 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 the Company'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; the Company'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 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 Rapport's intellectual property

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protections; and risks related to the competitive landscape for Rapport's product candidates; as well as other risks described in "Risk Factors," in the Company's Annual Report on Form 10-K 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. Any forward-looking statements represent Rapport's views only as of today and should not be relied upon as representing its views as of any subsequent date. 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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