Palisades Therapeutics (PT), a woman-owned and operated, clinical stage, life sciences company focused on the development of immunologic-based therapies for the prevention and treatment of disease, announced today that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application’s plan to proceed in proposed trials for its lead small molecule, PT150, in the treatment of patients diagnosed with COVID-19 in a Phase II/III outpatient clinical trial setting.
PT150 is in development for the treatment and prevention of respiratory viral infections, including SARS-CoV-2 Infection (COVID-19). The study: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE II/III STUDY TO ASSESS THE EFFICACY AND SAFETY OF PT150 IN ADULT COVID-19 OUTPATIENTS is being conducted in collaboration with a study team from the Veterans Administration (VA).
Palisades Therapeutics has been receiving guidance from BARDA (Biomedical Advanced Research Development Authority) Management to develop PT150 as a therapeutic for COVID-19. BARDA has now labeled the PT drug development program as “HIGHLY RELEVANT.” With BARDA’s help, PT now has regulatory clearance to start the clinical studies which have been supported by an extensive body of preclinical work performed by scientists at Colorado State University. The preclinical research in pre-print form can initially be reviewed at bioRxiv https://www.biorxiv.org/content/10.1101/2021.02.20.432110v1 and has been submitted for peer reviewed publication. The related and supporting pre-IND studies address mechanisms in acute COVID-19 lung infections, the involvement of viral infection of the brain and related neuroinflammation, and the impact of community and hospital-acquired bacterial co-infections.
PT is now being positioned for an “Other Transaction Agreement” (OTA) with BARDA. BARDA uses OTAs, a type of flexible, strategic partnership between the government and industry, to foster innovation and promote collaboration. OTAs help BARDA identify and attract nontraditional commercial firms or consortia to partner with the government. By positioning PT for an OTA, this encourages entities like PT to not only focus on the COVID program, but also include the other indications where the drugs in PT’s platform show efficacy that fit within BARDA’s organizational medical countermeasure targets (i.e., pandemic antivirals and biothreat pathogens).
With new SARS-CoV-2 variants emerging and the continued global impact of COVID-19, the mechanism of lead drug PT150 includes a focus on the host, to help neutralize the virus, regardless of the variant. The PT150 oral therapeutic could be the answer for an urgently needed therapy for patients everywhere.
In hamsters infected with SARS-CoV-2, a primary model for human COVID-19, PT150 demonstrated downregulation of ACE2 and TMPRSS2, the key molecules for SARS-CoV-2 entry into cells.
The PT platform should also have prophylactic and treatment properties against Influenza A given that TMPRSS2 is also a primary protease utilized by Influenza A in human airway cell infections. Beyond SARS and Influenza, in associated studies, PT150 platform compounds have broad spectrum antiviral activities in several different viral families as well as against diverse bacterial pathogens including MRSA. Thus, PT150 and its analogs have broad spectrum activities against many different human pathogens, viral and bacterial.
Palisades Therapeutics has developed a “First-in-Class” drug platform focused on novel mechanisms of action (MOAs) to neutralize the COVID-19 virus.
During the November 2020 NIH SARS-CoV-2 Antiviral Therapeutics Summit, NIH confirmed that while vaccines (i.e.: Pfizer Inc. NYSE: PFE and Johnson & Johnson NYSE: JNJ) will be extremely helpful in combating the virus, there is also a significant need for oral therapeutics that could be easily 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 spread of the virus in the population, but could reduce the numbers of infected people requiring hospitalization and dependence on costly IV antiviral medications. PT150, an orally administered small molecule, if approved for emergency 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 (e.g.,Tamiflu).
In the in vitro work in human bronchial cells performed by Jonna L.B. Westover, Ph.D.at Utah State University, the PT150 drug was very successful in demonstrating efficacy in neutralizing the SARS-CoV-2 virus. The in vivo study, performed in the NIH-approved hamster model of COVID-19, by investigators Ronald Tjalkens, PhD and Richard Slayden, PhD, at Colorado State University, confirmed successful anti-viral activity and mechanism of action. 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 of PT150, equivalent to the expected human dosing, maintained vigor and body weight indistinguishable from uninfected controls and their lungs showed markedly reduced lung injury and more rapid resolution of the injury by the end of the study. PT posits that these results will translate to human airway cell protection and minimized risk of severe pneumonia.
Additional, possibly synergistic, MOAs derive from the PT150 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. PT thus notes that the PT150 drug is intended as an early intervention in just-diagnosed, mild/early infections, not for severe infections requiring hospitalization (in which patients transition to overactive exaggerated immune activation).
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. The PT lead candidate, PT150 has completed multiple phase 1 and 2 studies for a CNS indication. PT re-purposed PT150 as an anti-viral drug with an extensive expanded platform of related therapeutic drugs that in early stages are showing potentially greater efficacy in these early in vitro analyses. PT has been working with NIH/NIAID over the past 4 years as PT developed its platform, showing activity across many pathogenic viruses, including MERS, Ebola, HIV and Influenza.
The complete data is being shared confidentially with FDA, NIH, Tech Watch, BARDA, ACTIV (Accelerating COVID-19 Therapeutics Interventions and Vaccines) and of course the VA/DoD. The data can also be shared with companies interested in the program under a CDA. The protocol for the PT planned clinical study was written by the Physician Scientists at The Veterans Medical Research Foundation (VMRF).
PT has an extensive patent landscape, both domestic and International, with priority dates back to 2015 across multiple molecules. 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.
Treatment with an effective, easily administered oral drug would allow patients to shorten time to viral clearance, diminish risk of spread, lessen hospitalization and get back to work and normal life sooner. The study IND application is cleared by FDA under an active IND through the CTAP Coronavirus Treatment Acceleration Program.
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About Palisades Therapeutics
The Palisades Therapeutics mission is to create, develop and protect new products and technologies that have the potential to significantly improve patients’ lives. PT companies have a unique paradigm. PT is 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.