GluN2B modulators(Janssen R&D)

- Data will be presented at the London International Cough Symposium on July 18, 2024 - 54,958,289 adult patients in the USA were analyzed for cough-related diagnoses and treatments in the EHR Integrated Database from EVERSANA® - The analysis indicates 2.19% of the adult population suffers from refractory chronic cough - De-identified patient-level data by geography enables efficient targeting of Phase 2b clinical trial enrollment and commercial modeling for proposed label opportunity CAMBRIDGE, Mass., July 09, 2024 (GLOBE NEWSWIRE) -- 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