CAMBRIDGE, Mass. — Seyltx, a clinical-stage biotherapeutics company, has announced new preclinical data showing that its lead compound, Ifenprodil, demonstrates strong potential for treating chronic cough. The findings, which will be presented at the American Cough Conference on June 7, are expected to guide optimized dosing strategies for the company’s upcoming Phase 2 crossover trials, slated for 2026.
Ifenprodil is a highly selective NMDA receptor antagonist that targets the GluN2B subunit with more than 200-fold specificity. It is being developed for refractory chronic cough (RCC) and chronic cough linked to idiopathic pulmonary fibrosis (IPF). In a previously completed Phase 2a trial for IPF-related cough, an exploratory low dose of 20 mg three times daily (TID) led to a statistically significant 39% reduction in objective cough frequency after 12 weeks, alongside improvements in patient-reported outcomes.
New non-human primate (NHP) studies, conducted in partnership with Yale University, show that higher doses of Ifenprodil are likely to deliver greater therapeutic effects without reaching receptor saturation. In these studies, PET scans measured GluN2B receptor occupancy following intravenous dosing. The data revealed that a dose equivalent to 20 mg in humans resulted in 50% receptor occupancy, while an 80 mg dose could reach up to 80% occupancy, which is expected to enhance efficacy compared to the 20 mg dose used in the earlier trial.
Guinea pig studies further supported these results. Oral administration of Ifenprodil at human-equivalent doses ranging from 20 to 160 mg reduced cough counts by 39% to 74% following exposure to citric acid, a common cough-inducing agent. The lowest dose mirrored outcomes seen in the previous human trial, while doubling the dose to 40 mg resulted in a 56% reduction. The highest tested dose showed the most pronounced suppression at 74%, still within safety margins. Notably, the antitussive effect remained durable for up to eight hours, despite decreasing systemic drug levels, suggesting sustained target engagement.
The combined findings indicate that a 40 to 80 mg TID dosing regimen may provide the greatest benefit in future human trials, with the potential for reformulating the therapy into a once-daily version.
Seyltx CEO Dr. Dietrich Stephan described the findings as a significant advance in the company’s efforts to develop an effective, non-addictive treatment for chronic cough. “These results confirm Ifenprodil’s robust antitussive properties and give us the data we need to fine-tune our clinical strategy. We’re optimistic about its potential as a monotherapy that addresses the brain’s central cough reflex pathway.”
Dr. Stephan added that Ifenprodil’s mechanism of action may allow it to be used across various chronic cough etiologies and in combination with future peripheral therapies. The company aims to integrate the new data into the design of its next clinical studies, bringing it closer to delivering a new therapy for patients struggling with chronic, treatment-resistant cough.
