Axalbion Doses First Patient in Phase 2 Study of AX-8 for Chronic Cough

Axalbion, a clinical-stage biopharmaceutical company headquartered in Manchester, UK, and Mountain View, California, has announced the administration of the first dose to a patient in the second segment of their Phase 2 clinical trial for chronic cough treatment using their lead compound, AX-8. AX-8 is an innovative oral agonist specifically targeting the transient receptor potential melastatin 8 (TRPM8) ion channel. To support the ongoing trial and future Phase 3 planning, Axalbion has secured additional funding from both existing and new investors.

Michael Kitt, MD, CEO of Axalbion, expressed his satisfaction with the progress, highlighting the promising results from the first part of the study. AX-8 demonstrated a significant and sustained reduction in cough frequency, particularly among patients experiencing severe throat discomfort, a prevalent symptom in chronic cough sufferers. These findings were presented at the American Thoracic Society (ATS) 2023 International Conference.

Following these encouraging results, Axalbion initiated the second part of the study. This phase focuses on patients with chronic cough who also experience moderate-to-severe throat discomfort, as they are deemed most likely to benefit from AX-8. The trial adopts a randomized, double-blind, placebo-controlled, crossover design to assess the efficacy and safety of AX-8 in approximately 50 patients with refractory or unexplained chronic cough (RCC/UCC).

In this trial, participants will receive 40 mg of AX-8 or a matching placebo three times daily, spaced about four hours apart, for two weeks. This will be followed by a seven-day washout period before switching treatments for another two weeks. AX-8 is administered as an orally disintegrating tablet placed on the tongue. The primary measure of efficacy will be the change in cough frequency from baseline, adjusted for placebo effects, using an objective cough recording device. The trial is being conducted across multiple centers in the United Kingdom and is slated for completion by the second half of 2025.

TRPM8, the target of AX-8, is found in many sensory fibers in the upper airways. Axalbion's approach involves activating these fibers with AX-8 to normalize sensitivity in chronic cough patients, thereby reducing coughing and throat irritation. The significance of TRPM8 was underscored by the awarding of the 2021 Nobel Prize in Physiology or Medicine to David Julius and Ardem Patapoutian for their work on thermal and mechanical transducers, including TRPM8. Since its identification in 2002, TRPM8 has been extensively studied and recognized as a potential target for alleviating various symptoms and conditions. Research in animal models has shown that activating TRPM8 can reduce sensory hypersensitivity in peripheral neuropathy, inflammation, and itching.

Chronic cough, defined as a cough lasting more than eight weeks, often includes bouts of severe coughing triggered by throat irritation. This condition affects a significant number of patients, especially those in specialized cough clinics, and has a substantial impact on quality of life. Notably, there are no approved treatments for chronic cough in the United States, leaving a considerable unmet need. Over 26 million people in the U.S. suffer from chronic cough, with a substantial subset experiencing refractory or unexplained chronic cough lasting more than a year.

Axalbion, founded in December 2016, is a private clinical-stage biotechnology company dedicated to developing treatments for chronic cough. Based in Manchester, a region noted for its respiratory research excellence, Axalbion continues to advance its innovative therapies to address this significant medical need.