Rapport Therapeutics 公告 RAP-219 双相躁狂 II 期试验达到主要和次要终点，拟推进 III 期

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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):
October 20, 2026
Rapport Therapeutics, Inc.
(Exact name of Registrant as Specified in Its Charter)
Delaware
001-42121
88-0724208
(State or Other Jurisdiction
of Incorporation)
(Commission
File Number)
(IRS Employer
Identification No.)
99 High Street
Suite 2100
Boston
,
Massachusetts
02210
(Address of Principal Executive Offices)
(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:
☐
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:
Title of each class
Trading
Symbol(s)
Name of each exchange
on which registered
Common Stock, $0.001 par value per share
RAPP
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 October 20, 2026, Rapport Therapeutics, Inc. (the “Company” or “Rapport”) issued a press release titled “Rapport Therapeutics Announces Positive Topline Results from its Phase 2 Trial of
RAP-219
for the Treatment of Bipolar Mania.” A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form
8-K.
Also, on October 20, 2026, the Company plans to host a conference call and live webcast to discuss topline data from its Phase 2 trial of
RAP-219
for the treatment of bipolar mania. The Company will make available a copy of the presentation from the webcast on the “Investors” page of the Company’s website at www.rapportrx.com and is furnished as Exhibit 99.2 to this Current Report on Form
8-K.
The information under this Item 7.01, including Exhibit 99.1 and Exhibit 99.2 hereto, is being furnished herewith and shall not be deemed “filed” for the 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, nor shall such information be deemed incorporated by reference in any filings under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, except as expressly set forth by specific reference in such filings.
Item 8.01.
Other Events.
On October 20, 2026, the Company announced positive topline results from its Phase 2 trial of
RAP-219
for the treatment of bipolar mania. The topline results, as well as additional corporate updates, are summarized below.
Phase 2 Results and Development Plans
On October 20, 2026, the Company announced positive topline results from its Phase 2 trial of
RAP-219
in adults experiencing acute mania associated with bipolar I disorder (“BD”). The trial met its primary endpoint, with
RAP-219
achieving a
3.1-point
placebo-adjusted improvement in the Young Mania Rating Scale (“YMRS”) total score at Week 3 (mean reduction from baseline of 15.4 points with
RAP-219
versus 12.3 points with placebo (p=0.045)), and
RAP-219
was well tolerated. These results establish clinical
proof-of-concept
for
RAP-219
and its novel TARP
g
8-selective mechanism in bipolar mania, supporting progression to Phase 3 trials which are expected to begin in the second half of 2027.
This randomized, double-blind, placebo-controlled Phase 2 trial, conducted in the United States, enrolled 253 adults with bipolar I disorder experiencing an acute manic episode (YMRS≥25 at baseline). During the screening period, all treatments indicated for BD and all anxiolytics and hypnotics, regardless of the indication, were discontinued. Lorazepam was allowed as a rescue medication at protocol-defined doses, and its use required an adverse event (“AE”) to be recorded, regardless of whether the symptom(s) were judged to be due to a
pre-existing
condition or disease manifestation.
Eligible patients received
RAP-219
0.75 mg once daily (following a
two-
or
four-day
titration) or placebo for three weeks in an inpatient setting. Mean baseline YMRS total score was 36.9 in the
RAP-219
arm and 35.8 in the placebo arm. Topline efficacy and safety data reported are from the three-week treatment period. Safety data from the eight-week post-treatment period will be presented at a future medical conference.
RAP-219
Demonstrated Statistically Significant Improvement in Manic Symptoms
●
The trial met its primary endpoint, with
RAP-219
achieving a statistically significant
3.1-point
least squares (“LS”) mean improvement over placebo in YMRS total score at Week 3 (p=0.045).
●
RAP-219–treated
patients had an LS mean decrease of 15.4 points in YMRS total score at Week 3 from a baseline of 36.9.
●
All 11 YMRS items improved on
RAP-219
compared to placebo at Week 3, with improvements in irritability, thought content, disruptive-aggressive behavior, and sexual interest reaching nominal significance (p<0.05).
●
RAP-219
showed progressive improvement in the placebo-adjusted YMRS scores over the
3-week
treatment period (0.9 at Week 1, 2.2 at Week 2, and 3.1 at Week 3).
●
RAP-219
also demonstrated a statistically significant improvement in mania severity score versus placebo at Week 3 as measured by the Clinical Global Impression—Bipolar Version mania severity scale, the pre-specified secondary endpoint (0.4; p=0.024).
RAP-219
was well-tolerated
During the three-week treatment period, based on safety and tolerability data, as of the interim database lock on September 16, 2026:
●
The incidence of treatment-emergent adverse events (“TEAEs”) was similar between
RAP-219
and placebo (51.6% vs 52.8%), as was the incidence of psychiatric TEAEs (34.9% vs 33.1%).
●
All TEAEs were mild or moderate in severity, and there were no serious adverse events (“SAEs”); 3.2% of patients on
RAP-219
discontinued due to a TEAE compared with 0.8% placebo.
●
TEAEs observed in ≥5% of participants in either group were agitation, insomnia, restlessness, anxiety, headache, and nausea. Of these, nausea was the only TEAE that was reported ≥2x as often in participants on
RAP-219
compared to placebo.
●
The most common TEAE on RAP-219 was agitation, generally occurring in the first week and lasting a median duration of two days in both the RAP-219 and placebo groups. In both groups, this was considered unrelated in >80% of patients.
●
Adverse effects commonly associated with current bipolar mania medications, including orthostatic hypotension, akathisia, and extrapyramidal symptoms were not reported. Somnolence was reported less often with
RAP-219
(0.8%) than placebo (3.1%).
The below safety analysis set includes all randomized participants who have received at least one dose of study drug
(RAP-219
or placebo).
Treatment Period TEAE Summary
Placebo (N=127)
RAP-219
(N=126)
Any TEAE, n (%)
67 (52.8)
65 (51.6)
TEAEs leading to drug discontinuation
1 (0.8)
4 (3.2)
TEAEs leading to dose reduction
1 (0.8)
0
Mild TEAEs
31 (24.4)
33 (26.2)
Moderate TEAEs
36 (28.3)
32 (25.4)
Severe TEAEs
0
0
SAEs
0
0
Any Psychiatric TEAE, n (%)
42 (33.1)
44 (34.9)
TEAEs in
≥
5% of participants in
either group, n(%), and treatment
relatedness
Placebo (N=127)
RAP-219
(N=126)
All
Treatment Related
All
Treatment Related
Agitation
12 (9.4)
2 (1.6)
21 (16.7)
4 (3.2)
Insomnia
19 (15.0)
1 (0.8)
18 (14.3)
4 (3.2)
Restlessness
10 (7.9)
0
11 (8.7)
2 (1.6)
Anxiety
7 (5.5)
1 (0.8)
9 (7.1)
1 (0.8)
Headache
13 (10.2)
6 (4.7)
7 (5.6)
1 (0.8)
Nausea
2 (1.6)
1 (0.8)
7 (5.6)
4 (3.2)
The Company enrolled 253 patients in the randomized trial, of which, 127 patients were in the placebo group and 126 received
RAP-219.
Of those patients enrolled,
thirty-one
patients (24.6%) in the
RAP-219
group discontinued the treatment, compared with fifteen (11.8%) in the placebo group. The most common reason for treatment discontinuation was withdrawal of consent (16.7%
RAP-219,
4.7% placebo). Reasons given for withdrawal of consent
(RAP-219,
placebo) were: personal reasons or subject decision (7, 2), family reasons (6, 3), wanted to leave the inpatient unit (5, 0), worsening symptoms or wanted to receive care elsewhere (3, 1).
Next Steps and Upcoming Milestones
The Company plans to meet with the U.S. Food and Drug Administration (“FDA”) in the first quarter of 2027 to discuss the Phase 2 data and registrational trial design for
RAP-219
in adults experiencing acute mania associated with BD. Initiation of two Phase 3 trials of
RAP-219
in acute bipolar mania is expected in the second half of 2027. Additional data from the Phase 2 trial will be presented at a future medical meeting.
Upcoming milestones include:
●
Focal onset seizures (“FOS”): FOCUS 1 and FOCUS 2 pivotal Phase 3 trials are enrolling.
●
FOS open-label long-term safety trial: Initial data from the long-term open-label extension of the Phase 2a trial in focal onset seizures are expected in the fourth quarter of 2026.
●
Bipolar mania:
End-of-Phase
2 Meeting with the FDA expected in the first quarter of 2027; initiation of two Phase 3 pivotal trials expected in the second half of 2027.
●
Primary generalized tonic-clonic seizures (“PGTCS”): Phase 3 trial is expected to begin in the first half of 2027.
●
Long-acting injectable (“LAI”): Phase 1 pharmacokinetic data for a long-acting injectable formulation of
RAP-219
are expected in the third quarter of 2027.
●
RAP-641:
Phase 1 preliminary results are expected in the second half of 2027.
●
Financial position: As of June 30, 2026, the Company had $436.1 million in cash, cash equivalents and
short-term
investments, excluding restricted cash, expected to fund operations into the second half of 2029, beyond expected topline data from the Company’s Phase 3 program in focal onset seizures.
Forward-Looking Statements
This Current Report on Form
8-K
contains “forward-looking statements” within the meaning of Section 27A of the Securities Act and Section 21E of the Exchange Act. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will” and “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 FOS, PGTCS and bipolar mania, including the initiation, timing, progress, results and future data releases of the Company’s ongoing and planned clinical trials, including the long-term open-label extension of the Phase 2a trial in FOS, the FOCUS 1 and FOCUS 2 pivotal Phase 3 trials, the Phase 1 trial for a long-acting injectable formulation of
RAP-219,
the Phase 1 trial for
RAP-641
and the Phase 3 trial of
RAP-219
in PGTCS; expectations and timing of upcoming regulatory interactions, including an
End-of-Phase
2 Meeting with the FDA for
RAP-219
and the anticipated planning activities for potential Phase 3 trials in bipolar mania; expectations for a LAI formulation of
RAP-219;
the potential of the Company’s RAP technology platform; expectations for the efficacy, tolerability, and commercial potential of
RAP-219;
and expectations for the Company’s uses of capital, expenses and financial results, including its expectations regarding cash runway into the second half of 2029.
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 FDA 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.
Item 9.01.
Financial Statements and Exhibits.
(d) Exhibits
Exhibit
No.
Description
99.1
Press Release issued by Rapport Therapeutics, Inc. on October 20, 2026, furnished herewith.
99.2
Corporate presentation of Rapport Therapeutics, Inc., furnished herewith.
104
Cover Page Interactive Data File (embedded within 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.
Rapport Therapeutics, Inc.
Date: October 20, 2026
By:
/s/ Troy Ignelzi
Troy Ignelzi
Chief Financial Officer

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EX-99.1
2
d185134dex991.htm
EX-99.1
EX-99.1
Exhibit 99.1
Rapport Therapeutics Announces Positive Topline Results from its Phase 2 Trial of
RAP-219
for the Treatment of Bipolar Mania
The trial met the primary and secondary endpoints with
statistically significant placebo-adjusted improvements at Week 3 in the YMRS total score (3.1 points; p=0.045) and
CGI-BP
Severity of Mania score (0.4 points; p=0.024)
RAP-219–treated
patients had a
15.4-point
mean reduction
in YMRS total score from baseline at Week 3
All 11 items measured by the YMRS improved numerically compared to placebo at Week 3, with
improvements in irritability, thought content, disruptive-aggressive behavior, and sexual interest reaching nominal significance
RAP-219
was well tolerated; all treatment emergent adverse events during the treatment period were mild or moderate
Company to host a conference call today at 8:00 a.m. ET
BOSTON and SAN DIEGO, October 20, 2026 (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 and psychiatric disorders, today announced positive topline results from
its Phase 2 trial of
RAP-219
in adults with acute bipolar mania. The trial met its primary endpoint, with
RAP-219
achieving a
3.1-point
placebo-adjusted improvement in the Young Mania Rating Scale (YMRS) total score at Week 3 (mean reduction from baseline of 15.4 points with
RAP-219
versus 12.3
points with placebo (p=0.045).
RAP-219
was well-tolerated, with no severe treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) observed over the treatment period. These results establish
clinical
proof-of-concept
for
RAP-219
and its novel TARP
g
8-selective
mechanism in bipolar mania, supporting progression to Phase 3 trials which are expected to begin in the second half of 2027.
“For people with bipolar disorder, the challenge isn’t just finding a treatment that’s efficacious. It’s finding one they can tolerate
and stay on,” said Abraham N. Ceesay, chief executive officer of Rapport. Side effects drive discontinuation, and discontinuation drives relapse.
RAP-219
has the potential to break that cycle with the
first new mechanism of action for bipolar mania in decades. Together with our positive Phase 2 focal epilepsy data, these results strengthen
RAP-219’s
profile across each indication we are pursuing and
show it delivering on its potential as a
pipeline-in-a-product
with two indications that both represent multibillion dollar
market opportunities. We look forward to engaging with the FDA on Phase 3 in bipolar mania, alongside our ongoing Phase 3 epilepsy programs.”
This
randomized, double-blind, placebo-controlled Phase 2 trial, conducted in the United States, enrolled 253 adults with bipolar I disorder (BD) experiencing an acute manic episode (YMRS≥25 at baseline). During the screening period, all treatments
indicated for BD and all anxiolytics and hypnotics were discontinued. Lorazepam was allowed as a rescue medication at protocol-defined doses, and its use required an AE to be recorded, regardless of whether the symptom(s) were judged to be due to a
pre-existing
condition.
Eligible patients received 0.75 mg of
RAP-219
once
daily (following a
two-
or four- day titration) or placebo for three weeks in an inpatient setting. Mean baseline YMRS total score was 36.9 in the
RAP-219
arm and 35.8
in the placebo arm. Topline efficacy and safety data reported are from the three-week treatment period. Safety data from the eight-week post-treatment period will be presented at a future medical conference.
RAP-219
Demonstrated Statistically Significant Improvement in
Manic Symptoms
•
The trial met its primary endpoint, with
RAP-219
achieving a
statistically significant
3.1-point
least squares (LS) mean improvement over placebo in YMRS total score at Week 3 (p=0.045).
•
RAP-219–treated
patients had an LS mean decrease of 15.4 points in
YMRS total score at Week 3 from a baseline of 36.9.
•
All 11 YMRS items improved on
RAP-219
compared to placebo at Week 3, with
improvements in irritability, thought content, disruptive-aggressive behavior, and sexual interest reaching nominal significance (p<0.05).
•
RAP-219
showed progressive improvement in the placebo-adjusted YMRS
scores over the
3-week
treatment period (0.9 at Week 1, 2.2 at Week 2, and 3.1 at Week 3).
•
RAP-219
also demonstrated a statistically significant improvement in
mania severity score versus placebo at Week 3 as measured by the Clinical Global Impression—Bipolar Version
(CGI-BP)
mania severity scale, the
pre-specified
secondary endpoint (0.4; p=0.024).
RAP-219
Was Well-Tolerated
During the three-week treatment period, based on safety and tolerability data
*
:
•
The incidence of treatment-emergent adverse events (TEAEs) was similar between
RAP-219
and placebo (51.6% vs 52.8%), as was the incidence of psychiatric TEAEs (34.9% vs 33.1%).
•
All TEAEs were mild or moderate in severity, and there were no serious adverse events (SAEs); 3.2% of patients on
RAP-219
discontinued due to a TEAE compared with 0.8% placebo.
•
TEAEs occurring in ≥5% of participants in either group
(RAP-219
vs
placebo) were agitation (16.7% vs 9.4%), insomnia (14.3% vs 15.0%), restlessness (8.7% vs 7.9%), anxiety (7.1% vs 5.5%), headache (5.6% vs 10.2%), and nausea (5.6% vs 1.6%). Those considered treatment related by the investigator were agitation (3.2%
vs 1.6%), insomnia (3.2% vs 0.8%), restlessness (1.6% vs 0%), anxiety (0.8% vs 0.8%), headache (0.8% vs 4.7%), and nausea (3.2% vs 0.8%).
•
The most common TEAE on
RAP-219
was agitation, generally occurring in the
first week and lasting a median duration of two days in both the
RAP-219
and placebo groups. In both groups, this was considered unrelated in >80% of patients.
•
Adverse effects commonly associated with current bipolar mania medications, including orthostatic hypotension,
akathisia, and extrapyramidal symptoms were not reported. Somnolence was reported less often with
RAP-219
(0.8%) than placebo (3.1%).
“In this
proof-of-concept
study,
RAP-219
demonstrated statistically significant improvement across measures of mania symptoms as well as a favorable tolerability profile,” said Jeffrey Sevigny, M.D., chief medical officer of Rapport.
“This is important because tolerability issues lead many patients to discontinue their therapies. These results continue to build our confidence in the safety profile of
RAP-219,
and the insights learned
from this study will guide us in optimizing the Phase 3 design in bipolar mania. Finally, we are deeply grateful to everyone who made this study possible, including participating patients and their families, the investigators and site staff, and our
dedicated employees.”
“There hasn’t been a new mechanism to treat bipolar mania in decades. In this study,
RAP-219
achieved statistically significant improvement in manic symptoms with an encouraging tolerability profile, underscoring the promise of this novel mechanism,” said Gary Sachs, M.D., founding director of
the Bipolar Clinic and Research Program at Massachusetts General Hospital and associate clinical professor of psychiatry at Harvard Medical School. “Importantly, clinical benefit was seen consistently across all measures, with the greatest
improvements in symptoms that tend to drive hospitalization for acute mania patients. What is encouraging about the tolerability profile is what was not seen on
RAP-219--the
somnolence, akathisia, and extrapyramidal symptoms that often cause patients to discontinue treatment. Based on these results,
RAP-219
has the
potential to become a mainstay of treatment for acute mania.”
Next Steps and Upcoming Milestones
Rapport plans to meet with the U.S. Food and Drug Administration (FDA) in the first quarter of 2027 to discuss the Phase 2 data and registrational trial design
for
RAP-219
in bipolar mania. Initiation of two Phase 3 trials of
RAP-219
in acute bipolar mania is expected in the second half of 2027. Additional data from the Phase 2
trial will be presented at a future medical meeting.
Upcoming milestones include:
•
Focal onset seizures (FOS): FOCUS 1 and FOCUS 2 pivotal Phase 3 trials are enrolling.
•
FOS open-label long-term safety trial: Initial data from the long-term open-label extension of the Phase 2a trial
are expected in the fourth quarter of 2026.
•
Bipolar mania:
End-of-Phase
2
meeting with the FDA expected in the first quarter of 2027; initiation of two Phase 3 pivotal trials expected in the second half of 2027.
•
Long-acting injectable (LAI): Phase 1 pharmacokinetic (PK) data for an LAI formulation of
RAP-219
are expected in the third quarter of 2027.
•
Primary generalized tonic-clonic seizures (PGTCS): Phase 3 trial is expected to begin in the first half of 2027.
•
RAP-641:
Phase 1 preliminary results are expected in the second half of
2027.
•
Financial position: As of June 30, 2026, Rapport had $436.1 million in cash, cash equivalents and
short-term investments, excluding restricted cash, expected to fund operations into the second half of 2029, beyond expected topline data from the Company’s Phase 3 program in focal onset seizures.
[
*
Safety and tolerability data as of interim database lock, September 16, 2026.]
Conference Call Information
Rapport Therapeutics will
host a conference call and live webcast at 8:00 a.m. ET / 5:00 a.m. PT on October 20, 2026, to discuss the data and provide a business update. Individuals interested in listening to the live conference call may do so by dialing (800)
715-9871
for U.S and Canadian callers and (646)
307-1963
for other locations and reference conference ID 3120573, or from the webcast link in the “Investors”
section of the Company’s website at www.rapportrx.com. A webcast replay will be available in the “Investors” section of the Company’s website for 90 days following the completion of the call.
About the Young Mania Rating Scale (YMRS)
The Young
Mania Rating Scale (YMRS) is a clinician-administered tool used to measure the severity of manic symptoms in people with bipolar disorder. It is the most widely used rating scale in mania research. The YMRS assesses 11 core symptoms of mania:
elevated mood, increased activity and energy, sexual interest, sleep, irritability, speech, thought disorder, thought content, disruptive or aggressive behavior, appearance, and insight. Four of these symptoms (irritability, speech, thought content,
and disruptive or aggressive behavior) are weighted more heavily to reflect their clinical significance. Clinicians rate each symptom from a clinical interview and the patient’s reported symptoms over the preceding 48 hours. Total scores range
from 0 to 60, with higher scores indicating more severe mania.
About the Clinical Global Impression–Bipolar Version
(CGI-BP)
The Clinical Global Impression–Bipolar Version
(CGI-BP)
is a clinician-rated scale adapted from the widely used Clinical Global Impression scale to assess illness severity and change in people with bipolar disorder. Clinicians rate mania, depression, and overall bipolar illness separately. The
CGI-BP
mania severity score reflects the clinician’s overall judgment of how severe a patient’s manic symptoms are, based on clinical experience with patients with bipolar disorder. Scores range from 1
(normal, not ill) to 7 (among the most extremely ill patients), with higher scores indicating more severe mania.
CGI-BP
mania severity is commonly used as a complement to symptom-based scales such as the YMRS
by capturing the clinician’s overall view of illness severity.
About
RAP-219
RAP-219
is an investigational and potential
first-in-class,
clinical-stage TARP
g
8-specific
AMPA receptor (AMPAR) negative
allosteric modulator (NAM). Whereas AMPARs are distributed widely in the central nervous system, the receptor associated protein (RAP) TARP
g
8 is expressed only in discrete brain regions, including the
hippocampus and neocortex, where focal seizures often originate. By contrast, TARP
g
8 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 TARP
g
8, the Company believes
RAP-219
has
pipeline-in-a-product
potential and is evaluating the compound as a potential treatment for patients with focal onset seizures, primary generalized tonic-clonic seizures and bipolar mania. A
long-acting injectable formulation of
RAP-219
is also in development and could be the first of its kind in epilepsy.
About Rapport Therapeutics
Rapport Therapeutics is a
clinical-stage biotechnology company dedicated to discovering and developing small molecule precision medicines for patients with neurological and psychiatric disorders. The Company’s founders made pioneering discoveries related to the
function of receptor associated proteins (RAPs) in the brain, which form the basis of Rapport’s RAP technology platform. The platform 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,
which is designed to
achieve neuroanatomical specificity through selective targeting of a RAP expressed only in discrete regions of the brain. The pipeline is anchored by the Company’s epilepsy portfolio, including FOS and primary generalized tonic-clonic
seizures, as well as bipolar mania. The Company is also advancing additional discovery and preclinical programs leveraging its platform, including in chronic pain and migraine and in hearing and vestibular disorders.
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.
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 FOS, PGTCS and bipolar mania, including the initiation, timing, progress, results and future data releases of our ongoing and planned clinical trials, including the long-term open-label extension of the Phase 2a trial in FOS, the
FOCUS 1 and FOCUS 2 pivotal Phase 3 trials, the Phase 1 trial for a long-acting injectable formulation of
RAP-219,
the Phase 1 trial for
RAP-641
and the Phase 3 trial of
RAP-219
in PGTCS; expectations and timing of upcoming regulatory interactions, including an
End-of-Phase
2 Meeting with the FDA
for
RAP-219
the anticipated planning activities for a potential Phase 3 trial in bipolar mania; expectations for a LAI formulation of
RAP-219;
the potential of the
Company’s RAP technology platform; expectations for the efficacy, tolerability, and commercial potential of
RAP-219;
and expectations for the Company’s uses of capital, expenses and financial
results, including its expectations regarding cash runway into the second half of 2029.
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
investors@rapportrx.com

----- d185134dex992.htm -----
EX-99.2
3
d185134dex992.htm
EX-99.2
EX-99.2
Exhibit 99.2 R RAP AP--2 21 19 9 P Ph ha ase se 2 2 iin n B Biip pol ola
ar r M Ma an niia a T Top oplliin ne e R Re esul sult ts s Webcast Presentation OCTOBER 20, 2026
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, will, 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 focal onset seizures, primary generalized tonic-clonic seizures, bipolar mania and peripheral neuropathic pain, including the initiation, timing,
progress and results of the ongoing, planned and future clinical trials; expectations for the efficacy, tolerability, and commercial potential of RAP-219; the potential multi-billion dollar market opportunity for RAP- 219 in focal onset seizures,
primary generalized tonic-clonic seizures and bipolar mania, if approved; expectations for the development of a long-acting injectable formulation of RAP-219; the potential of the Company’s RAP technology platform; the achievement of any
milestones in connection with the Tenacia collaboration; and expectations for the Company’s uses of capital, including its cash runway expectations into the second half of 2029. Forward-looking statements 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; risks relating to the Company's ability to execute on its strategy, including obtaining the requisite regulatory approvals on the expected timelines,
if at all; uncertainties relating to preclinical and clinical development activities; risks relating to the Company's dependence on third parties to conduct clinical trials, manufacture its product candidates and develop, commercialize its product
candidates, if approved, and more; risks relating to the Company's ability to attract, integrate and retain key personnel; risks relating to the Company’s business operations; risks relating 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 relating to regulatory developments and approval processes of the U.S. Food and Drug Administration and comparable
foreign regulatory authorities; risks relating to establishing, defending 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 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 the Company's subsequent fillings with the
Securities and Exchange Commission. Any forward-looking statements represent the Company's views only as of today and should not be relied upon as representing its views as of any subsequent date. 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. 2
Agenda Company and RAP-219 Overview 01 Abe Ceesay, Chief Executive
Officer Bipolar Mania Phase 2 Trial Topline Results 02 Jeffrey Sevigny, MD, Chief Medical Officer KOL Perspective 03 Gary Sachs, MD, Founding Director, Bipolar Clinic and Research Program, Massachusetts General Hospital; Associate Clinical Professor
of Psychiatry, Harvard Medical School Near-term Catalysts and Financial Overview 04 Troy Ignelzi, Chief Financial Officer Closing Remarks 05 Abe Ceesay, Chief Executive Officer 06 Q&A 3
Company and RAP-219 Overview Abe Ceesay Chief Executive Officer, Rapport
Phase 2 results support advancing RAP-219 to Phase 3 in bipolar mania
Statistically significant Well tolerated improvement in mania symptoms Met primary endpoint: statistically significant All TEAEs mild or moderate; incidence was YMRS reduction vs placebo similar to placebo Greater improvement on all YMRS single-item
Low discontinuation rate due to AEs scores with RAP-219 vs placebo; key items achieving nominal significance Differentiated tolerability profile Met key secondary endpoint: statistically significant improvement in severity of mania Phase 2 data
supports advancing RAP-219 to Phase 3 AEs: Adverse Events, YMRS: Young Mania Rating Scale, TEAEs: Treatment emergent AEs 5
RAP-219 circuit-selective approach to bipolar mania Targets
glutamatergic hyperactivity in cortico-limbic networks Bipolar mania is characterized by increased glutamate levels Increased Cerebral Metabolism in Manic Patients a,b,c and hypermetabolism in cortico-limbic networks Relative to Healthy Controls
Glutamate signaling is primarily mediated by AMPA receptors, which accounts for most fast excitatory transmission in the d brain RAP-219 selectively modulates TARPγ8-dependent AMPA receptor activity, potentially reducing excitatory
glutamatergic drive in limbic neuronal populations that correspond to manic network hyperactivity Lithium, valproate, and lamotrigine - approved therapies for bipolar - act in part by attenuating glutamatergic transmission, including reducing
glutamate release and e,f downregulating AMPA receptor function a b c d e Brooks III et al., Psychiatry Res (2010); Yüksel & Öngür, Biological Psychiatry (2010); Gigante et al., Bipolar Disord (2012); Traynelis et al., Pharmacol
Rev (2010); Du et f al., J Neurosci (2004); Lee et al., Epilepsia (2008); AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; TARPy8: transmembrane AMPA receptor regulatory protein gamma-8 6
Bipolar mania: large market underserved by current treatments Metabolic
and neurological side effects lead to U.S. patient population lack of compliance & limit long-term chronic use ~8M Adults (18+) with bipolar disorder 1L 2L 3L+ 490K 490K 660K ~3.6M Atypical APD or mood Add or switch to mood Trial another
atypical Diagnosed patients stabilizer; two drugs stabilizer ASM APD or switch ASM often combined (e.g; Lithium + ASM) in severe mania ~1.6M >1.1M Bipolar mania patients 2L+ patients in acute bipolar mania Merikangas et al. Arch Gen Psychiatry
(2007); Kato et al., J Affect Disord (2019); Kessler et al., Int J Methods Psychiatr Res (2012); Ringeisen et al., Int J Methods Psychiatr Res (2023); Jain et al., Adv Ther (2022); Internal Market Research 2026. APD: antipsychotic drug; ASM:
antiseizure medication; 2L: second line; 3L: third line 7
Patients need a new mechanism that can break the relapse cycle Unmet
need: an effective treatment for bipolar mania with a tolerability profile that supports adherence RAP-219 could break the cycle Novel mechanism (TARPγ8 AMPAR NAM) Statistically significant improvements in mania symptoms No evidence of AEs
typically leading to discontinuation of current treatments No blood-level monitoring No DDIs 8
Clinical presentation of mania CORE SYMPTOMS Elevated or irritable mood
and raised energy, lasting a week or more Required for DSM-5 PLUS: 3 OR MORE OF THESE (4 if mood is only irritable) Grandiosity Pressured speech Racing thoughts Decreased need for sleep Distractibility Risky, high-consequence behavior Increased
activity COMMONLY ASSOCIATED SYMPTOMS Agitation Disruptive-aggressive behavior Psychotic and mixed features Anxiety Substance use Suicide risk Impaired insight 9
Bipolar Mania Phase 2 Trial Topline Results Jeff Sevigny, M.D. Chief
Medical Officer, Rapport 10
RAP-219 bipolar mania Phase 2 trial met primary and secondary
endpoints; RAP-219 was well tolerated STATISTICALLY SIGNIFICANT IMPROVEMENT IN MANIC SYMPTOMS WITH CONSISTENT BENEFIT ACROSS ALL MEASURES All YMRS items favor 15.4 points 3.1 points 0.4 points 1 RAP-219 Four items with nominal placebo-adjusted YMRS
placebo-adjusted CGI-BP-S mean YMRS improvement from significance: irritability, content, improvement at Week 3 mania improvement at Week 3 baseline at Week 3 (RAP-219) disruptive-aggressive behavior, vs −12.3 placebo p=0.045 (primary) p=0.024
(secondary) and sexual interest RAP-219 WAS WELL TOLERATED IN PATIENTS WITH BIPOLAR MANIA Low rates of discontinuation Low somnolence and Overall incidence of TEAEs No severe TEAEs or SAEs ✓✓✓✓ due to AEs: 3.2% RAP-219
including psychiatric TEAEs dizziness; no akathisia/ on treatment vs 0.8% placebo were generally balanced EPS between groups 1 : Pre-specified exploratory endpoint; AE: Adverse Event; CGI-BP-S: Clinical Global Impression Bipolar Mania Severity Scale
(CGI-BP-S Mania); EPS: extrapyramidal symptoms; SAE: Serious Adverse Event; TEAE: Treatment Emergent Adverse Event; YMRS: Young Mania Rating Scale; data presented as LS mean and LS mean differences 11
Phase 2 proof-of-concept trial in bipolar mania 1 Week 3 Weeks 8 Weeks
56 Day Safety Follow up Period Up to 7 Day 21 Day Inpatient Treatment Period Weekly Following Last Dose Screening Period RAP-219 or Placebo Day -7 to Day -1 1 Day 1 to Day 21 22 Day 22 to Day 77 Start of End of End of Trial Treatment Treatment Key
Entry Criteria Dose Regimen § Adults with mania associated with bipolar I disorder, with or § Participants randomized 1:1:2 to RAP-219 with 2-or 4-day titration without mixed features, with or without psychotic symptoms (2T or 4T, pooled
for efficacy analysis), or placebo § At least one prior documented manic episode (with or without § Maintenance dose: 0.75mg psychotic symptoms) that required treatment, within 5 years prior § Participants washed out of any medication
indicated for bipolar to Visit 1 1 disease and any anxiolytic/hypnotic prior to randomization § YMRS total score ≥25 at Screening and Baseline Endpoints § Primary: YMRS total score, change from baseline to Week 3 § Secondary:
CGI-BP Severity of Illness–Mania, change from baseline to Week 3 NCT07046494; CGI-BP: Clinical Global Impression Bipolar Mania; YMRS: Young Mania Rating Scale 12
Patient disposition and analysis sets 431 Total Screened 253 Randomized
Placebo RAP-219 Randomized & Dosed: Reasons given for withdrawal of n=127 n=126 2 consent (RAP-219, placebo) : (Full and Safety analysis set) • personal reasons or subject decision (7, 2) Discontinued Treatment: 15 (11.8%) Discontinued
Treatment: 31 (24.6%) 1 1 • family reasons (6, 3) AE : 1 (0.8%) AE : 4 (3.2%) • wanted to leave the inpatient Lack of Efficacy: 1 (0.8%) Lack of Efficacy: 0 2 2 unit (5, 0) Withdrawal of consent : 6 (4.7%) Withdrawal of consent : 21
(16.7%) • worsening symptoms or wanted Lost to follow-up: 0 Lost to follow-up: 0 to receive care elsewhere (3, 1) Protocol Non-compliance: 2 (1.6%) Protocol Non-compliance: 4 (3.2%) Other: 5 (3.9%) Other: 2 (1.6%) Completed: n=112 n=95 For
participants who discontinued treatment, all data before discontinuation were included in the model and missing data was handled implicitly under a missing at random assumption Safety Analysis Set = Full Analysis Set (all 253 randomized participants
were dosed). Completed treatment = completed the 21-day double-blind treatment period. 1 AEs that led to treatment discontinuation: agitation (1 participant on placebo, not related), agitation/anxiety (1 participant on RAP-219, possibly related),
and shingles, left ankle sprain, and suicidal ideation (1 participant each on RAP-219, not related). One participant on placebo reported suicidal ideation (not related) that did not lead to discontinuation. 13
Patient demographic and baseline characteristics Both arms balanced
across key characteristics Placebo (N=127) RAP-219 (N=126) Age, years; mean (SD) 43.5 (11.7) 44.3 (11.4) Male; n (%) 68 (53.5%) 74 (58.7%) White; n (%) 67 (52.8%) 68 (54.0%) Black or African American; n (%) 54 (42.5%) 55 (43.7%) Weight, kg; mean
(SD) 88.0 (19.8) 87.2 (19.6) Time since initial diagnosis, years; mean (SD) 19.5 (11.0) 19.4 (11.7) Current Episode; n (%) With mixed features 4 (3.1%) 4 (3.2%) With psychotic features; n (%) 51 (40.2%) 48 (38.1%) Duration, days; mean (SD) 26.8
(16.6) 29.5 (18.4) Baseline YMRS, mean (SD) 35.8 (4.9) 36.9 (5.1) Baseline CGI-BP-S Mania, mean (SD) 5.0 (0.5) 5.0 (0.6) CGI-BP-S: Clinical Global Impression-Bipolar Version-Severity; SD: standard deviation; YMRS: Young Mania Rating Scale
14
Statistically significant improvement on primary endpoint (YMRS) 3.1
points improvement vs placebo at Week 3 (p=0.045) LS Mean Difference at Week 3: -12.3 -3.1 -15.4 p = 0.045 *p<0.05 vs placebo RAP-219 0 −7.0 −11.8 −15.4 Placebo 0 −6.2 −9.6 −12.3 −0.9 −2.2
−3.1* LSM Difference Efficacy analyses were performed using the Full Analysis Set (FAS). The FAS includes all randomized participants who have received at least one dose of study drug (RAP-219 or placebo). Participants were evaluated according
to their randomized treatment assignment. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with fixed effects of treatment group, visit, treatment by visit interaction, and stratification factor (psychotic
symptoms), and the corresponding baseline YMRS as a covariate. LS means and differences are rounded. LS: Least Squares; LSM: LS 15 Mean; YMRS: Young Mania Rating Scale IMPROVEMENT
Greater improvement on all YMRS single-item scores with RAP-219 Key
items achieving nominal significance SINGLE-ITEM ANALYSIS SUMMARY Prespecified Exploratory Endpoint → All YMRS single-item scores numerically improved on RAP-219 vs placebo at Week 3 → Nominally significant improvements vs placebo:
→ Irritability and disruptive-aggressive behavior at weeks 2 and 3 → Content and sexual interest at week 3 Full Analysis Set. Each item analyzed with MMRM (treatment, visit, treatment-by-visit interaction, stratification factor, baseline
item score). Prespecified exploratory endpoint; p-values nominal, not adjusted for multiplicity. Items ordered by Week 3 LS mean difference; diamonds = nominal p<0.05. † Items scored 0–8 (others 0–4). YMRS: Young Mania Rating
Scale 16
Statistically significant improvement on secondary endpoint (CGI-BP-S
Mania) 0.4-point improvement vs placebo at Week 3 (p=0.024) LS Mean Difference at Week 3: -0.4 p = 0.024 *p<0.05 vs placebo RAP-219 0 −0.6 −1.0 −1.6 Placebo 0 −0.5 −0.8 −1.2 Efficacy analyses were performed
using the Full Analysis Set (FAS). The FAS includes all randomized participants who have received at least one dose of study drug (RAP-219 or placebo). Participants were evaluated according to their randomized treatment assignment. Change from
baseline was analyzed using a mixed model for repeated measures (MMRM) with fixed effects of treatment group, 17 visit, treatment by visit interaction, and stratification factor (psychotic symptoms), and baseline CGI-BP-S Mania score as a covariate.
Values are LS means. LS: Least Squares IMPROVEMENT
RAP-219 was well tolerated All TEAEs mild or moderate; low rate of
discontinuation due to TEAEs Treatment Period TEAE Summary Placebo (N=127) RAP-219 (N=126) Any TEAE, n (%) 67 (52.8) 65 (51.6) → The overall incidence of TEAEs and of psychiatric TEAEs leading to drug discontinuation 1 (0.8) 4 (3.2) TEAEs was
similar between groups TEAEs leading to dose reduction 1 (0.8) 0 → All TEAEs were mild or moderate Mild TEAEs 31 (24.4) 33 (26.2) Moderate TEAEs 36 (28.3) 32 (25.4) → Overall TEAEs observed in ≥5% of participants in either group
were agitation, insomnia, Severe TEAEs 0 0 restlessness, anxiety, headache, and nausea SAEs 0 0 → Of these, nausea was the only TEAE that Any Psychiatric TEAE, n (%) 42 (33.1) 44 (34.9) was reported ≥2x as often in participants ZZ on
RAP-219 compared to placebo Placebo (N=127) RAP-219 (N=126) TEAEs in ≥5% of participants in either Treatment Treatment → The most common TEAE on RAP-219 was group, n(%), and treatment relatedness All All Related Related agitation,
generally occurring in the first week Agitation 12 (9.4) 2 (1.6) 21 (16.7) 4 (3.2) → Considered unrelated in >80% of patients Insomnia 19 (15.0) 1 (0.8) 18 (14.3) 4 (3.2) who reported agitation (both groups) Restlessness 10 (7.9) 11 (8.7) 2
(1.6) 0 → Median duration of events was 2 days Anxiety 7 (5.5) 1 (0.8) 9 (7.1) 1 (0.8) (both groups) Headache 13 (10.2) 7 (5.6) 1 (0.8) 6 (4.7) Nausea 2 (1.6) 1 (0.8) 7 (5.6) 4 (3.2) The Safety Analysis Set (SAS) includes all randomized
participants who have received at least one dose of study drug (RAP-219 or placebo). SAE: Serious Adverse Event; TEAE: treatment-emergent adverse event. Lorazepam was allowed as a rescue medication at protocol-defined doses, and its use required an
AE to be recorded, regardless of whether the symptom(s) were judged to be due to a 18 pre-existing condition.
Topline results recap RAP-219 met primary secondary endpoints and was
well-tolerated STATISTICALLY SIGNIFICANT IMPROVEMENT IN MANIC SYMPTOMS WITH CONSISTENT BENEFIT ACROSS ALL MEASURES All YMRS items favor 15.4 points 3.1 points 0.4 points 1 RAP-219 Four items with nominal placebo-adjusted YMRS placebo-adjusted
CGI-BP-S mean YMRS improvement from significance: irritability, content, improvement at Week 3 mania improvement at Week 3 baseline at Week 3 (RAP-219) disruptive-aggressive behavior, vs −12.3 placebo p=0.045 (primary) p=0.024 (secondary) and
sexual interest RAP-219 WAS WELL TOLERATED IN PATIENTS WITH BIPOLAR MANIA Low rates of discontinuation Low somnolence and No severe TEAEs or SAEs Overall incidence of TEAEs ✓✓✓✓ due to AEs: 3.2% RAP-219 dizziness; no
akathisia/ on treatment including psychiatric TEAEs vs 0.8% placebo EPS were generally balanced between groups 1 : Pre-specified exploratory endpoint; AE: Adverse Event; CGI-BP-S: Clinical Global Impression Bipolar Mania Severity Scale (CGI-BP-S
Mania); EPS: extrapyramidal symptoms; SAE: Serious Adverse Event; TEAE: Treatment Emergent Adverse Event; YMRS: Young Mania Rating Scale; data presented as LS mean and LS mean differences 19
Advancing RAP-219 in bipolar mania Regulatory and clinical activities
underway to support Phase 3 trials NEXT STEPS MODELED PK / RECEPTOR OCCUPANCY Efficacy and safety data establish proof-of-concept for a novel, differentiated mechanism 1Q 2027 End-of-Phase 2 meeting anticipated 2H 2027 Phase 3 program initiation
anticipated PHASE 3 ENHANCEMENT Higher dose: 1.25 mg achieves RO thresholds more quickly and higher RO at day 21 Expanded footprint: Ex-US geographies with strong historical signal in neuropsych trials Protocol optimization based on Phase 2 trial
insights 20
KOL Perspective Gary Sachs, M.D. Founding Director, Bipolar Clinic and
Research Program, Massachusetts General Hospital Assoc. Clinical Professor of Psychiatry, Harvard Medical School
Near-term Catalysts and Financial Overview Troy Ignelzi Chief Financial
Officer, Rapport
Multiple anticipated catalysts through 2027 1 Cash balance of $436.1M
(as of 6/30/26) expected to support Rapport into 2H 2029 1Q 2027 3Q 2027 End-of-Phase 2 2H 2027 RAP-219 meeting with FDA Phase 1 PK results RAP-219 Phase 3 program initiation RAP-219 1H 2027 Open-label long- 2H 2027 RAP-219 term safety trial Phase 3
trial initial data RAP-641 preliminary initiation results 2026 2027 1 Cash, cash equivalents, and short-term investments, excluding restricted cash (unaudited) 23
Closing Remarks Abe Ceesay Chief Executive Officer, Rapport
Building a precision neuroscience franchise PIVOTAL-STAGE
PIPELINE-IN-A-PRODUCT Program Preclinical Phase 1 Phase 2 Phase 3 Focal onset seizures Bipolar mania PGTCS PGTCS ~1.6M patients RAP-219 1 EPILEPSY Bipolar mania ~0.8M patients LAI 1 ~1.8M patients α6β4 α9α10 1 Based on 30-40% of
patient population that is drug-resistant (those who continue to experience recurring seizures despite failing 2 or more antiseizure medications) 25
Questions & Answers