TRPM8

CRANBURY, N.J., Sept. 17, 2024 /PRNewswire/ -- IVIEW Therapeutics Inc., a clinical-stage biotechnology company dedicated to advancing innovative treatments for ocular diseases, today announced the completion of patient recruitment for its Phase 1/2 clinical trial evaluating IVW-1001, a novel TRPM8 agonist delivered via ophthalmic eyelid wipe, for the treatment of signs and symptoms of dry eye disease. The company anticipates reporting topline data in the first quarter of 2025. Advancing Toward Promising Results "We are thrilled to have reached this significant milestone in our clinical development program for IVW-1001," said Houman Hemmati, MD, PhD, Chief Medical Advisor at IVIEW Therapeutics Inc. "Completing patient enrollment brings us one step closer to potentially offering a new therapeutic option for individuals suffering from dry eye disease. We are eagerly awaiting the trial results and remain optimistic about the potential impact on patient care." A Step Forward in Innovative Ophthalmic Treatments Bo Liang, PhD, MBA, Co-founder, Chairman, and CEO of IVIEW Therapeutics Inc., commented, "The completion of patient recruitment ahead of schedule is a testament to the dedication of our clinical team and the interest from the ophthalmic community. IVW-1001's novel mechanism of TRPM8 activation and its innovative delivery through an ophthalmic eyelid wipe could offer a differentiated treatment for dry eye disease worldwide. We look forward to sharing our findings as soon as they are available." About IVIEW Therapeutics Inc. IVIEW Therapeutics Inc. is a clinical-stage biotechnology company focusing on innovative ophthalmic therapeutics. Driven by the pursuit of cutting-edge science, we aim to develop differentiated products that fulfill unmet medical needs. We invest in novel mechanisms of action and advanced drug delivery technology platforms to bring forward assets with potentially superior target product profiles. Our innovative portfolio of small molecules and gene therapy assets covers dry eye, myopia, conjunctivitis, glaucoma, and presbyopia. Located in Cranbury, New Jersey, IVIEW operates a state-of-the-art 11,045 sq. ft. laboratory and office space in the Princeton area. For additional information, please visit our website at . SOURCE IVIEW Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

MANCHESTER, England & MOUNTAIN VIEW, Calif.--( BUSINESS WIRE )--Axalbion, a clinical-stage biopharmaceutical company focused on developing novel medicines to treat cough, announced that the first patient has been dosed in the second part of a Phase 2 proof-of-concept, randomized, placebo-controlled clinical study in chronic cough with AX-8, its lead compound. AX-8 is a potent and selective oral agonist of the transient receptor potential melastatin 8 (TRPM8) ion channel. The company has raised additional financing from existing and new investors to support the trial execution and Phase 3 planning. “We are pleased to announce that Axalbion has launched the second part of its Phase 2 clinical trial with AX-8 in chronic cough, a disease with significant unmet needs,” said Michael Kitt, MD, chief executive officer of Axalbion. “In the first part of this study, AX-8 showed promising results with a robust and sustained reduction in cough frequency, particularly in patients experiencing the greatest throat discomfort, a distressing symptom observed in most chronic cough patients.” Data were presented in an oral session at the American Thoracic Society (ATS) 2023 International Conference. Based on the initial positive findings, the company initiated Part 2 of the study of AX-8 in patients with chronic cough with moderate-to-severe throat discomfort (i.e., those with a throat discomfort visual analog scale score ≥50mm out of 100mm), who are the most likely to benefit from treatment with AX-8. The Phase 2 trial is a randomized, double-blind, placebo-controlled, crossover study evaluating the efficacy and safety of AX-8 in approximately 50 patients with refractory or unexplained chronic cough (RCC/UCC). Patients will receive 40 mg of the drug or matching placebo thrice daily (as opposed to twice daily in Part 1) approximately four hours apart for two weeks, followed by a seven-day washout period, before crossing over to the opposite treatment for two weeks. AX-8 is formulated as an orally disintegrating tablet placed on the tongue. Cough frequency will be assessed with an objective cough recording device. The primary efficacy endpoint will be the placebo-adjusted change in cough frequency compared to baseline. The study will take place at multiple centers in the U.K. and is expected to be completed by the second half of 2025. For more information, please visit clinicaltrials.gov: NCT04866563 . About TRPM8 and AX-8 TRPM8 is expressed in many of the sensory fibers innervating the upper airways. Axalbion believes that activating TRPM8-expressing fibers with AX-8, a potent TRPM8 agonist, will normalize the upper airway sensitivity in chronic cough patients, decreasing coughing and irritation of the throat. David Julius and Ardem Patapoutian were awarded the 2021 Nobel Prize in Physiology or Medicine for their discoveries of thermal and mechanical transducers, including the discovery of TRPM8. Since its cloning in 2002, extensive research has identified TRPM8 as a potential target to relieve symptoms or cure several diseases. Animal models have shown that activation of TRPM8-expressing fibers in the skin inhibits sensory hypersensitivity in peripheral neuropathy and inflammation, as well as itching. About Chronic Cough Chronic cough is defined as a cough lasting for more than eight weeks, often occurring in bouts. More than 80% of patients in tertiary cough clinics have throat irritation which triggers cough bouts, defining a population with oropharyngeal hypersensitivity potentially responding to a topical locally acting drug such as AX-8. After potential triggers such as gastro-intestinal reflux disease (GERD) and asthma have been excluded or treated, cough still remains a significant and common problem for many patients. Chronic cough has a substantial impact on quality of life, for example, around half of female patients having urinary stress incontinence. There are no approved drugs for the treatment of chronic cough in the U.S., making it a significant unmet need affecting approximately 26 million people in the U.S. alone, with approximately three million having RCC/UCC lasting for more than a year and approximately six million having RCC/UCC lasting more than eight weeks and less than one year. About Axalbion Axalbion is a privately held, clinical-stage biotechnology company developing novel medicines for the treatment of chronic cough. The company, founded in December 2016, is based in Manchester, United Kingdom, a region known for its centers of excellence in respiratory research. For further information, please visit www.axalbion.com .

Menthol sensing appeared long before cold sensing, suggesting distinct activation modes that can be disentangled, paving the way for new pain therapies without adverse thermal side effects. Chronic pain affects millions worldwide, and current treatments often rely on opioids, which carry risks of addiction and overdose. Non-addictive alternatives could revolutionize pain management, and new research targeting the human protein which regulates cold sensations, brings scientists closer to developing pain medications that don't affect body temperature and don't carry the risks of addiction. Research published in Science Advances on June 21, led by Wade Van Horn, professor in Arizona State University's School of Molecular Sciences and Biodesign Center for Personalized Diagnostics, has uncovered new insights into the main human cold and menthol sensor TRPM8 (transient receptor potential melastatin 8). Using techniques from many fields like biochemistry and biophysics, their study revealed that it was a chemical sensor before it became a cold temperature sensor. "If we can start to understand how to decouple the chemical sensing of cold from actual cold sensing, in theory, we could make side-effect-free drugs," said Van Horn whose research focuses on membrane proteins involved in human health and disease. "By understanding the evolutionary history of TRPM8, we hope to contribute to designing better drugs that offer relief without the dangerous side effects associated with current painkillers." When a person touches a metal desk and it feels cold, the human body activates TRPM8. For cancer patients who are on certain kinds of chemotherapeutics, touching a desk can hurt. TRPM8 is also involved in many other types of pain as well, including chronic neuropathic and inflammatory pain. By further understanding this specificity of the chemical sensing of cold versus physically sensing cold, scientists can target relief without triggering the temperature regulation side effects often seen in TRPM8 clinical trials for pain treatments. In the research, the team used ancestral sequence reconstruction, a time machine for proteins of sorts, compiling the family tree of TRPM8 that exists today and then used that information to determine what the proteins from long-extinct animals might have looked like. Using computational methods to resurrect ancestral primate, mammalian, and vertebrate TRPM8, the researchers were able to understand how TRPM8 has changed over hundreds of millions of years by comparing the sequences of current proteins to predict the sequences of their ancient ancestors. Additionally, the combination of lab experiments and computational studies enable the researchers to identify critical places in TRPM8 that allow a more clear understanding of temperature sensing, which can be tested in subsequent experiments. "Comparative dynamics analysis of ancestral and human TRPM8 also supports the experimental data and will allow us to identify critical sites in temperature sensing, which we will be testing soon," said Banu Ozkan, professor in ASU's Department of Physics, who was involved in the study. The team then expressed these ancestral TRPM8s in human cells and characterized them using various cellular and electrophysiology techniques. "Ancestral protein-based studies allow us to focus on the lineage of most interest, such as human TRPM8, to alleviate concerns arising in drug discovery from speciation differences, like in mice and humans," said first author on the study Dustin Luu, an ASU School of Molecular Sciences doctoral alumnus, and current postdoctoral fellow in ASU's Biodesign Center for Personalized Diagnostics. Luu continued: "We discovered that surprisingly menthol sensing appeared way before cold sensing. The difference in appearance and attenuation of these activation modes suggest they are separate and can be disentangled with further research enabling new pain therapies without the adverse side effect in thermal sensing and thermal regulation, which has plagued TRPM8-targeted clinical trials." As science continues to uncover the mysteries of our biological mechanisms, studies like this exemplify how evolutionary biology and modern pharmacology can collaborate to address pressing medical needs and improve the quality of life for those suffering from chronic pain.