The Veterans Medical Research Foundation (VMRF) is collaborating with New Jersey-based Palisades Therapeutics (PT) to launch a clinical trial on an oral therapeutic that has shown promising results against COVID-19 in in vitro and in vivo preclinical studies. The VMRF and Department of Defense (DoD) have been collaborating with PT for the past five years in the development of PT’s clinical stage therapeutics.
The PT platform is a “First-in-Class” drug platform focused on novel mechanisms of action (MOAs) to neutralize the COVID-19 virus.
During the November 6th NIH SARS-CoV-2 Antiviral Therapeutics Summit, NIH confirmed that vaccines (i.e.: Pfizer Inc. NYSE: PFE and Johnson & Johnson NYSE: JNJ) will be extremely helpful in combating the virus, but that there is also a significant need for oral therapeutics that could be provided to every person who tests positive, in the early stages of viral infection. An oral therapeutic that is simple to administer would not only potentially reduce population spread, but could reduce the numbers of infected people requiring hospitalization and dependence on costly IV anti-viral medications. The oral treatment PT drug, if approved for use, would be targeting more than 80% of the patients who test positive and may more rapidly neutralize the virus. Thus, SARS-CoV-2 infection could have a similar prevention/treatment paradigm to influenza for which there is a two pronged approach of vaccination and oral treatment (Tamiflu).
In initial in vitro work in human bronchial cells performed by Jonna L.B. Westover, Ph.D.at Utah State University, the PT drug was very successful demonstrating efficacy in neutralizing the virus. The in vivo study, performed in the NIH-approved hamster model of COVID-19, by Ronald Tjalkens, PhD at Colorado State University, confirmed successful anti-viral activity. SARS-CoV-2 animals infected with virus and receiving placebo were moribund and lost weight. Their lungs showed advanced stage broncho-interstitial pneumonia similar to severe/fatal human SARS-CoV-2 infection. Infected animals receiving daily oral dose PT drug, equivalent to the expected human dosing, maintained vigor and bodyweight indistinguishable from uninfected controls and their lungs showed markedly reduced lung injury and more rapid resolution of the injury by end of study. We posit that these results will translate to human airway cell protection and minimized risk of severe pneumonia. This work with significantly more detailed analyses will be ready for publication shortly.
MOAs derive from the drug being a potent modulator of steroidal hormone receptors, notably the androgen and glucocorticoid receptors. The MOAs exploit both pathways. Direct anti-viral activity comes from down-regulation of androgen receptor activity leading to suppression of TMPRSS2 (the primary protease needed for viral cell entry) and inhibition of ACE2 (the cell's viral receptor). The PT drug acts indirectly as well. In the face of elevated circulating cortisol characteristic of acute viral infection, blockade of the glucocorticoid receptor leads to immune system support during the early stages of infection. We thus note that the drug is intended as an early intervention in just-diagnosed, mild/early infections, not for severe infections requiring hospitalization (in which patient’s transition to overactive immune states).
The PT therapeutics are part of a platform of broad spectrum therapeutics with our clinical stage drug having a human safety profile established through prior Phase 2 clinical studies. Our lead candidate has completed multiple phase 1 and 2 studies for a CNS indication. We re-purposed it as an anti-viral with an extensive expanded platform of therapeutics that are early stage showing potentially greater efficacy in early in vitro analyses. We have been working with NIH/NIAID over the past 4 years as we developed our platform, showing efficacy across many viruses, including Mers-CoV, Ebola, and HIV.
PT expects the in vivo hamster model data will be published in early 2021 but meanwhile the data is being shared confidentially with FDA, NIH, Tech Watch, BARDA, ACTIV and of course the VA/DoD. The data can also be shared with companies interested in the project under a CDA. The protocol for our planned clinical proof of concept study was written by the Physician Scientists at The Veterans Medical Research Foundation (VMRF) and they are ready to start the study as soon as funding and FDA study approval are in place.
PT has an extensive patent landscape, both domestic and International, with priority dates back to 2015 across multiple molecules. PT has sufficient quantity of the drug manufactured for the planned clinical study. The drug has been produced in the past at a scale of over 200 kilos per batch. The process descriptions are available, including methods and impurities. The drug has been produced in both capsule and tablet form. The drug substance (API) and the drug product (capsules or tablets) have been produced on a commercial scale and the release methods are validated. Dr. James Bruno leads the PT CMC program.
While the rest of the world was focusing on a narrow MOA and the moderate to severe hospitalized patients, PT, with the help of the Federal agencies, realized that the focus should really be the majority of people who are diagnosed and experience mild symptoms. Treatment with an effective, easily administered oral drug would allow patients to shorten time to viral clearance, diminish risk of spread and get back to work and normal life sooner. We had the help of Dr. Robert Walker at BARDA to get us before Tech Watch and we had been doing CRADA’s with the DoD/VA. We addressed our plan for COVID-19 with the Physician/Scientists at VRMF, who agreed on the likely MOA’s and wanted to be a part of bringing this drug to the people who need it. The next step is moving the study protocol forward; it is currently under FDA review under an active IND through the CTAP Coronavirus Treatment Acceleration Program.
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About Palisades Therapeutics
Our mission is to create, develop and protect new products and technologies that have the potential to significantly improve patients’ lives. Our companies have a unique paradigm. We are like a “Brain Trust” of more than 75 leading scientists, physicians, clinicians, lawyers and professionals working together without salary, to change the world. We out-license or sell our products and intellectual property to third parties for global commercialization.
The Veterans Medical Research Foundation supports a rich diversity of scientific inquiry, assisting many principal investigators in the administration of a diverse list of studies. Many of the investigators associated with the Veterans Medical Research Foundation are considered to be among the nation's leading experts in their fields. These physicians and scientists have a passion for the scientific discovery that can be translated into practical application to benefit human health. This 'bench-to-bedside" approach has led to Veterans Medical Research Foundation breakthroughs in areas as diverse as shingles prevention, small pox, alcoholism and heart disease - breakthroughs that have had a direct impact on veterans' health and all have been extended to the general population.