Rapport Therapeutics Hosts Investor and Analyst Day; Provides Corporate Updates
- Phase 2a trial of RAP-219 in refractory focal epilepsy is fully enrolled with topline results expected in September 2025
- Strong safety profile from Phase 1 trials with no serious adverse events across 100 healthy volunteers
- Healthy cash position of $285.4M providing runway through end of 2026
- Multiple upcoming catalysts including expansion into bipolar mania indication
- Three patient discontinuations reported in Phase 1 trials
- Early-stage company with no approved products or revenue streams yet
Insights
Rapport's Phase 2a epilepsy trial fully enrolled with topline results expected in September 2025; early safety profile appears promising.
Rapport Therapeutics has reached a significant milestone with full enrollment in their Phase 2a trial of RAP-219 for refractory focal epilepsy, positioning them for topline results by September 2025. The trial design demonstrates scientific rigor by utilizing intracranial electroencephalography (iEEG) data from the RNS System to evaluate RAP-219's effect on long episodes (LEs), an objective biomarker that correlates with clinical seizures at a
The enrolled patient population appears well-representative of typical refractory epilepsy trial participants, with a median of 10 clinical seizures per 28 days and patients taking a median of 3 concomitant antiseizure medications - indicating a truly treatment-resistant population. This strengthens the validity of any potential efficacy signals in the upcoming readout.
The consolidated safety data from the Phase 1 trials (n=64) is particularly encouraging. RAP-219 demonstrated a differentiated safety profile with only Grade 1-2 treatment-emergent adverse events, no serious adverse events, and no clinically significant laboratory, vital sign, or ECG abnormalities. The most common side effects (headache, dry mouth, brain fog, and fatigue) align with typical CNS drug profiles but at potentially lower frequency than existing antiseizure medications. The limited discontinuations (only 3 out of 64 participants) further support a favorable tolerability profile, which is crucial for chronic neurological conditions where treatment adherence directly impacts outcomes.
Rapport's strong cash position of $285.4M provides runway through 2026, supporting multiple value-driving clinical readouts.
Rapport Therapeutics is executing a well-structured clinical development strategy for RAP-219 across multiple indications. The company's lead program in refractory focal epilepsy has reached full enrollment, with topline results expected in September 2025. This represents a critical value-inflection point that could validate their precision neuroscience platform approach.
The company's financial position is robust, with
Rapport's trial design for the epilepsy indication demonstrates scientific sophistication by using objective biomarkers (long episodes measured via intracranial EEG) in addition to the traditional clinical seizure endpoints. This dual-endpoint approach provides both mechanistic validation and clinical relevance, potentially de-risking the program. The baseline characteristics of enrolled patients (median of 10 clinical seizures per 28 days) represent a population with significant disease burden where even modest improvements could be clinically meaningful. The consolidated Phase 1 safety data showing no serious adverse events and generally mild side effects positions RAP-219 favorably against existing antiseizure medications that often have significant tolerability issues limiting patient compliance.
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 02, 2025 (GLOBE NEWSWIRE) -- 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:
Phase 2a trial of RAP-219 in refractory focal epilepsy
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 to access RAP-219’s potential effect on long episodes (LEs), an objective biomarker shown to correlate with clinical seizures (CSs).
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.
Baseline Characteristics of First 14 Patients Enrolled
| Median (range) | Median (1st to 4th quartile range) | |||
| Age | 37 (20-61) | CS frequency per 28 days in 4-week prospective baseline | 10 (4.25-18.25) | |
| Sex (n) | 7F/7M | LE frequency per 28 days in 12-week baseline (8-week retrospective + 4-week prospective) | 51 (21-194) | |
| Age at first seizure | 19 (0.5-31) | Concordance between LEs and electrographic seizure (rated by an independent reviewer) | ||
| Years since RNS implantation | 4.4 (1.4-10.2) | Concomitant antiseizure medications | 3 |
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:
- Proportion of patients achieving ≥
30% reduction in LEs compared with 12-week baseline period - Median percent change in LE frequency compared with 12-week baseline period
Key secondary endpoint analysis:
- Median percent change in CS frequency compared with 4-week prospective baseline
- Proportion of patients achieving ≥
50% reduction in CSs compared with 4-week prospective baseline
Treatment-emergent adverse event (TEAE) incidence and grade
RAP-219 Phase 1 development update
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.
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:
- All TEAEs were Grade 1 or 2
- No serious adverse events (SAEs), nor clinically significant laboratory, vital signs, or electrocardiogram (ECG) abnormalities
- TEAEs occurred early in dosing and resolved without further action
- Most common TEAEs: headache (n=12), dry mouth (n=5), brain fog (n=5), and fatigue (n=5)
- Three discontinuations
Upcoming catalysts
- September 2025: RAP-219 Phase 2a topline readout in focal epilepsy
- Q3 2025: Initiation of RAP-219 Phase 2a trial in bipolar mania
- 2H 2025: Update on the Company’s diabetic peripheral neuropathic pain program
- 1H 2027: RAP-219 Phase 2a topline readout in bipolar mania
Cash runway guidance
As of March 31, 2025, Rapport reported
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 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 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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