Algernon Pharmaceuticals candidate NP-120, also known as Ifenprodil, is the drug we are advancing in our chronic cough and idiopathic pulmonary fibrosis (IPF) research program. NP-120 is a small molecule approved in Japan and South Korea to treat vertigo caused by ischemic stroke. Recent preclinical in vivo animal studies show that NP-120 compared favorably to the world’s leading two treatments for IPF (Nintedanib and Pirfenidone), reducing fibrosis by 56 percent.
We have recently concluded a Phase 2a study of Ifenprodil in patients with IPF and chronic cough. The trial met its co-primary endpoint with patients receiving Ifenprodil experiencing no worsening of their lung function, and significant improvements were seen in the frequency of their IPF-associated cough as well.
NP-120 is an N-methyl-D-aspartate (NMDA) receptor antagonist specifically targeting the NMDA-type subunit 2B (GluN2B). Ifenprodil prevents glutamate signaling. The NMDA receptor is found on many tissues including lung cells, T-cells, and neutrophils, and is expressed prominently in many parts of the brain. Although cough signals originate in afferent nerves in the lung and airway, the urge to cough is mediated in the brain, and the Company believes that inhibiting glutamate signaling can prevent the urge to cough regardless of the original stimulus. The Company also believes that pharmacological blockade of the NMDA receptor, specifically the NR2B subunit, on infiltrating neutrophils in interstitial lung disease can reduce inflammation and possibly reverse fibrosis. Further work to investigate the mechanism of action of NP-120 is ongoing.
Algernon has been issued a patent from the Canadian Intellectual Property Office (“CIPO”), No. 3101853, for the treatment of interstitial lung disease with NP-120 (“Ifenprodil”), entitled “Compositions and Methods for Treating Idiopathic Pulmonary Fibrosis”.
The invention claims treating interstitial lung disease, including idiopathic pulmonary fibrosis (“IPF”), with Ifenprodil. The base claims of the patent will be valid through 2038, excluding any patent term adjustments or extensions which may provide additional protection. The Company also has active patent applications for Ifenprodil for the same compositions and methods in the U.S., Europe, China, and Japan.
Algernon’s intellectual property strategy for its repurposed drug program includes protecting its compounds by filing patent applications covering method of use for new disease indications, as well as dosing and formulation. In addition, the Company has filed new composition of matter patents for novel salt forms of NP-120.
Chronic cough is a persistent condition that lasts at least eight weeks in adults or four weeks in children. It is a very common symptom of IPF, with at least 70 percent of IPF patients exhibiting a persistent, dry cough. Chronic cough can interrupt sleep, leading to exhaustion. Severe cases can cause vomiting, light-headedness, or rib fractures. Currently, there is no regulatory approved treatment for this condition in the U.S.A.
According to market research and analysis provider IndustryARC, the cough remedies market size is estimated to increase to $2.05B during 2019-2024, growing at a CAGR of 6.64%.
IPF is a chronic type of lung condition characterized by a progressive and irreversible decline in lung function and scarring (fibrosis) of the lungs. There is no cure for IPF, and there are no procedures or medications that can remove the scarring from the lungs. At least 70%-80% of patients with IPF are additionally affected by a non-productive cough, which can often get worse on exertion.
According to research and consulting firm GlobalData’s latest report, the IPF market will increase to USD $3.2 billion by 2025 (from USD $900 million in 2015), a projected compound annual growth rate (CAGR) of 13.6 percent.
Ifenprodil was shown to have mediated anti-inflammatory responses and reduced pulmonary fibrosis in mouse models by 56 percent. In addition, Ifenprodil significantly reduced cough frequency and delayed onset in a guinea pig acute cough model.
We have recently concluded a Phase 2a study of Ifenprodil in patients with IPF and chronic cough. The trial met its co-primary endpoint with patients receiving Ifenprodil experiencing no worsening of their lung function, and significant improvements were seen in the frequency of their IPF-associated cough as well.
Algernon recently announced its plans for a 180 patient, 90-day Phase 2b clinical study of Ifenprodil for chronic cough to begin in Q4 of 2023. The company received feedback from the U.S. FDA agreeing with the proposed clinical plan.
The planned study design will include the following elements:
The U.S. FDA has also granted Orphan Drug Designation to Ifenprodil as a treatment for IPF. The next steps for the Company will be to file a pre-IND with the U.S. FDA and develop a clinical protocol.
We continue to review our Phase 2a data towards planning for the filing of a pre-IND application with the U.S. FDA for our Phase 2b IPF chronic cough trial. We will also file an additional application for Breakthrough Therapy Designation for Ifenprodil for chronic cough.
We have engaged several global experts in the areas of chronic cough and idiopathic pulmonary fibrosis research and have retained the following medical and scientific advisors.
Jacky Smith is a Professor of Respiratory Medicine at the University of Manchester and an Honorary Consultant at Manchester University NHS Foundation Trust. She runs a multi-disciplinary research team whose focus is on understanding mechanisms underlying pathological cough and a regional clinical service seeing patients with refractory chronic cough. She is also the Director of the NIHR Manchester Clinical Research Facility and Leads the Rapid Translational Incubator Theme of the NIHR Manchester Biomedical Research Centre.
In collaboration with Mr. Kevin McGuinness (clinical engineer), she has developed a novel method for semi-automated cough detection that has been licensed to a medical device company (Vitalograph Ltd) with whom she collaborates. The subsequent commercialization of this cough monitoring system has changed the standards by which novel cough therapies are evaluated in regulatory clinical trials. Moreover, the use of this system to quantify coughing in a study of patients attending her chronic cough clinic facilitated the discovery of a new class of efficacious anti-tussive therapy, P2X3 antagonists.
Dr. Dicpinigaitis is board-certified in Internal Medicine, Pulmonary Diseases and Critical Care Medicine. He is a faculty member of the Division of Critical Care Medicine at Montefiore Medical Center and is the founder and director of the Montefiore Cough Center, one of the few specialty centers in the world exclusively committed to the evaluation and management of patients with chronic cough.
He received his undergraduate education at New York University (NYU) where he graduated summa cum laude with a degree in biochemistry. He obtained his medical degree from the NYU School of Medicine and remained at NYU-Bellevue for internal medicine residency training. He completed a fellowship in pulmonary & critical care medicine at the Mount Sinai Medical Center in New York, immediately after which he came to Einstein/Montefiore.
In addition to experience in all aspects of clinical medicine within the spectrum of pulmonary and critical care, a major focus of Dr. Dicpinigaitis' clinical research for over 25 years has been in the area of cough. He has authored numerous peer-reviewed journal articles and book chapters on cough and is considered an authority on the performance of cough challenge studies in clinical research. He served as a co-author on cough management guidelines published by the American College of Chest Physicians as well as the European Respiratory Society and is the founder and chairman of the biannual American Cough Conference. Dr. Dicpinigaitis also serves as the Editor-in-Chief of the journal LUNG.
Dr. Kolb is the Moran Campbell Chair and Professor in Respiratory Medicine and Director of the Division of Respirology, McMaster University, Hamilton, Ontario, Canada. He is lead of the interstitial lung disease program, located at St. Joseph’s Healthcare Hamilton, where more than 1,500 patients with different types of fibrotic interstitial lung disorders are seen annually. His major research interests are the mechanisms of lung fibrosis, with a particular interest in the role of growth factors, matrix abnormalities and pulmonary vessel remodeling in disease progression.
He leads activities in biomarker development for lung fibrosis and is a Principal Investigator and steering committee member in numerous clinical trials. Dr. Kolb has authored over 150 peer-reviewed publications on different basic science and clinical topics. He is the Chief-Editor of the European Respiratory Journal, the flagship publication of the European Respiratory Society. He is also an editorial board member of American Journal of Respiratory and Critical Care Medicine, American Journal of Respiratory Cell and Molecular Biology, the European Respiratory Review and Respirology and serves on the Lung Injury & Repair Study Section for the National Institute of Health.
Discover articles and interviews about our companies and therapeutic research programs.
Read MoreWe continue to plan a Phase 1 trial for NP-251 (Repirinast) for chronic kidney disease. In a pre-clinical animal model of kidney fibrosis, Repirinast reduced fibrosis by 50% with statistical significance.
Learn MoreOur AP-188 (DMT) candidate is based on a naturally occurring psychedelic compound that has been shown in several preclinical studies to induce and increase neuroplasticity. We aim to repurpose psychedelic DMT as a potential new treatment for stroke and traumatic brain injury (TBI) patients.
Learn More
