Seyltx, Inc. (“Seyltx” or the “Company”), a
clinical-stage biopharmaceutical company developing a novel therapy
for the treatment of refractory chronic cough (“RCC”) and other
neuronal hypersensitivity indications including cough associated
with idiopathic pulmonary fibrosis (“IPF”), today announced the
results of a study performed that analyzed real world electronic
health record (“EHR”) data to determine the prevalence of
refractory chronic cough (“RCC”) in the adult population. Based on
this data, the Company believes that it can optimize enrollment in
its Phase 2b clinical trial and more accurately model the
commercial opportunity for a product candidate.
“Refractory chronic cough is a significant
disorder which often destroys the quality of life of those who
suffer. The disorder was defined as a clinical entity only about a
decade ago and we believe it is significantly under-diagnosed due
to still emerging physician awareness,” commented Dietrich A.
Stephan, Ph.D., President and Chief Executive Officer of Seyltx.
“In order to better define the market opportunity for this unmet
medical need, we decided to create a multivariate surrogate
diagnostic signature by which to accurately diagnose RCC in the
absence of an ICD10 code for RCC in the patient’s EHR. Having
created this diagnostic signature, we queried tens of millions of
health records to precisely understand the market opportunity as
well as geographical locations from which patients can be
efficiently enrolled into our SILINDA Phase 2b clinical trial.”
Clinical features commonly used by expert
physicians to arrive at an RCC diagnosis from among a broader
chronic cough population were identified through expert interviews.
The Company, together with Atropos Health, Inc., analyzed a total
data set of 94,400,624 patients for these cough-related diagnoses
and treatment data in the EHR Integrated Database from EVERSANA®, a
nationally representative EHR dataset. Records from January 1,
2015, to December 31, 2023, were used to define the prevalence. To
ensure there was sufficient follow-up data to articulate >8
weeks of coughing, the data set was restricted to patients who had
more than 6 months of total follow-up in the record. Finally, the
initial data set was restricted to adult patients aged 18-90. This
resulted in 54,958,289 patients forming the analysis group.
Patients were considered to have chronic cough if they had at least
one chronic cough ICD10 diagnosis code or any of the following over
at least 8 weeks: multiple cough diagnoses, multiple antitussive
records, multiple inhaled corticosteroid records, or multiple
expectorant records. Patients that had underlying pathologies were
excluded to arrive at patients with RCC. Key results are as
follows:
- Of the
54,958,289 patients who were aged 18-90, had associated gender
data, and had greater than 6 months of follow-up data, 3,467,086
patients met our clinical criteria for diagnosis with chronic cough
(6.31%).
- Of these
patients, 1,024,624 patients, or 34.65% of chronic cough patients,
met criteria that in our analysis defined them as RCC
patients.
- The proportion
of chronic cough patients who are defined as RCC is consistent with
estimates that generally hover at ~40% from other studies.
- 2.19% of the
adult population in the USA suffers from refractory chronic
cough.
- This translates
into approximately 5,900,000 adults in the USA alone suffering from
RCC using what is believed to be a conservative analytic
approach.
“Refractory chronic cough remains a huge unmet
clinical need across the globe, with devastating impact on
patients, predominantly women, as well as patients’ families,
friends and coworkers. Significant levels of anxiety, depression,
and social isolation are associated with RCC,” commented Peter
Dicpinigaitis, M.D., Professor of Medicine at the Albert Einstein
School of Medicine, a member of the Seyltx Scientific Advisory
Board, and a co-author of the study. “The economic impact of
chronic cough and RCC on the health system is immense. Cough is
among the most common complaints for which individuals seek
medical attention, accounting for as many as 30 million visits to
health care providers annually,” continued Dr. Dicpinigaitis.
“Seyltx is developing what I believe is a promising solution for
stubborn and refractory cough - a pill that targets the master
switch of the cough reflex in the brain but is non-narcotic and
non-sedating.”
The Company’s preclinical data with its product
candidate, ifenprodil, illustrates significant antitussive effects
at doses well below the no observed adverse event limit (“NOAEL”).
The completed Phase 2a clinical trial recapitulates and extends
upon the preclinical data by illustrating statistically significant
reductions in geometric mean cough count reduction. The Company
plans to dose the first patients in its Phase 2b clinical trial in
early 2025.
The Company will use the de-identified
patient-level data it has generated through this analysis to
identify high-volume clinical practices across the USA, and
subsequently across the globe, to increase the clinical trial
enrollment velocity with the goal of accelerating development of
its product candidate.
The results of this study will be presented on July 18, 2024, at
the London International Cough Symposium and published in the
Journal of Thoracic Disease.
About Ifenprodil
Ifenprodil, a highly selective GluN2B allosteric
antagonist, is in development for RCC and cough associated with
IPF. An open-label Phase 2a trial was performed that showed a ~40%
reduction in geometric mean cough counts (p<0.01) from baseline
at a 1 mg/kg/day dose, with 80% of patients responding as measured
by 24H counts by the VitaloJAK® device. Individual patient data in
this Phase 2a trial illustrated that 90% of patients responded as
measured by reductions in Cough Severity using Visual Analogue
Scale (“CS-VAS”) scores (p<0.001). Improvements were also seen
on the Leicester Cough Questionnaire (“LCQ”; p<0.05). Reductions
in 24H cough counts were equally seen in high and low cough count
patients, and the mean and median responses are similar, further
illustrating that a few outliers did not drive the overall
therapeutic effect of the trial cohort.
The GluN2B receptor, which is implicated in
transmission of sustained high-frequency firing from the vagal
afferent neurons to the cough center in the brain, is a rational
target for treating chronic cough. Non-selective NMDA receptor
antagonists have been evaluated in multiple pre-clinical and
clinical trials and have been shown to be antitussive, but these
non-selective NMDA channel blockers have associated dose-limiting
adverse events (“AEs”). These AEs are linked to the broad
expression of the NMDA receptor throughout the brain which are
responsible for a myriad number of functions. The Company was
founded on work from Johns Hopkins University where expression
profiling of the nucleus of the solitary tract in the medulla,
where the vagal afferent neurons terminate, identified GluN2B as a
target of interest. Ifenprodil is an approved drug in Japan and
South Korea but is considered a new chemical entity (“NCE”) in the
major global markets, allowing the Company to de-risk development
due to extensive safety. This, while simultaneously obtaining
maximum exclusivity and intellectual property protection. Seyltx
believes that its highly selective GluN2B antagonist has the
potential to reduce cough frequency in patients with RCC and
improve quality of life while limiting the AEs associated with
non-selective NMDA receptor blockade and by focusing on mitigation
of the relatively unique sustained high-frequency firing of the
vagal afferent neurons.
The Company is evaluating potential
opportunities to study ifenprodil in additional cough indications
where vagal afferent neuronal hypersensitivity plays an important
role such as cough associated with IPF.
About Seyltx
(www.seyltx.com)
Seyltx is a clinical-stage biopharmaceutical
company developing novel therapeutics for the treatment of RCC and
other neuronal hypersensitivity indications. The Company's product
candidate ifenprodil, recently acquired from Algernon
Pharmaceutical Corporation, has successfully completed a Phase 2a
trial in cough associated with IPF. Seyltx is planning a Phase 2b
program, named SILINDA (Selective IfenprodiL INhibition of NMDA),
which is expected to have the first patient enrolled in 2025.
Chronic cough is a cough lasting longer than
eight weeks. When the cause of chronic cough cannot be identified
or the cough persists despite treatment of all identified
associated causes, the condition is referred to as RCC. RCC is
associated with significant adverse physical, social, and
psychological effects on health and quality of life. Currently,
there is no specific therapy approved for RCC and treatment options
are limited.
The Company is exploring the potential use of
ifenprodil in other patient populations experiencing cough
hypersensitivity including cough associated with IPF.
Forward-Looking Statements
Certain statements contained in this news
release, other than statements of fact that are independently
verifiable at the date hereof, may constitute "forward-looking
statements" within the meaning of the U.S. Private Securities
Litigation Reform Act of 1995, as amended, and other applicable
securities laws. Forward-looking statements are frequently, but not
always, identified by words such as “expects,” “anticipates,”
“believes,” “intends,” “estimates,” “potential,” “possible,”
“projects,” “plans,” and similar expressions. Such statements,
based as they are on the current expectations of management,
inherently involve numerous important risks, uncertainties and
assumptions, known and unknown, many of which are beyond Seyltx's
control. Such statements include, but are not limited to, the
potential of ifenprodil to successfully treat RCC and other
hypersensitization-related disorders and benefit such patients,
Seyltx’s expectations related to its preclinical studies and
clinical trials, including the timing of initiation of and the
design of its Phase 2b clinical trial of ifenprodil in RCC, the
timing and outcome of interactions with regulatory agencies, the
potential activity and tolerability profile, selectivity, potency
and other characteristics of ifenprodil, including as compared to
other competitor candidates, especially where head-to-head studies
have not been conducted and cross-trial comparisons may not be
directly comparable due to differences in study protocols,
conditions and patient populations, the commercial potential of
ifenprodil, including with respect to patient population, pricing
and labeling, Seyltx’s financial position and sufficiency of cash
resources to bring through topline results with SILINDA, and the
potential applicability of ifenprodil and Seyltx’s GluN2B platform
to treat other disorders. Risk factors that may affect Seyltx’s
future results include but are not limited to: the benefits and
impact on its potential label of its non-cough count enrichment
strategy, estimates and projections regarding the size and
opportunity of the addressable RCC market for ifenprodil, the
ability to expand and develop its project pipeline, the ability to
obtain adequate financing, the ability of Seyltx to maintain its
rights to intellectual property and obtain adequate protection of
future products through such intellectual property, the impact of
general economic conditions, general conditions in the
pharmaceutical industry, the impact of the ongoing COVID-19
pandemic on Seyltx’s operations, plans and prospects, including to
the initiation and completion of clinical trials in a timely manner
or at all, changes in the regulatory environment in the
jurisdictions in which Seyltx does business, supply chain impacts,
stock market volatility, fluctuations in costs, changes to the
competitive environment due to consolidation, achievement of
forecasted burn rate, achievement of forecasted preclinical studies
and clinical trial milestones, reliance on third parties to conduct
preclinical studies and clinical trials for ifenprodil and that
actual results may differ from topline results once the final and
quality-controlled verification of data and analyses has been
completed. In addition, the length of Seyltx’s product candidate’s
development process and its market size and commercial value are
dependent upon a number of factors. Moreover, Seyltx’s growth and
future prospects are mainly dependent on the successful
development, patient tolerability, regulatory approval,
commercialization and market acceptance of its product candidate
ifenprodil and potentially other products. Consequently, actual
future results and events may differ materially from the
anticipated results and events expressed in the forward-looking
statements. Seyltx believes that expectations represented by
forward-looking statements are reasonable, yet there can be no
assurance that such expectations will prove to be correct. The
reader should not place undue reliance, if any, on any
forward-looking statements included in this news release. These
forward-looking statements speak only as of the date made, and
Seyltx is under no obligation and disavows any intention to update
publicly or revise such statements as a result of any new
information, future event, circumstances or otherwise, unless
required by applicable legislation or regulation.
CONTACT
Matt LaneInvestor RelationsMilestone Advisors,
LLCmatt@milestone-advisorsllc.com