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Principal Investigator: JODI K CRAIGO
Organization: CYTOAGENTS, INC.
Fiscal Year: 2022
Award: $1,000,000
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract
CytoAgents is developing GP1681 (beraprost-314d) to regulate the uncontrolled inflammatory response that can
result from viral infections. This inflammatory response is associated with increased disease severity, acute lung
injury (ALI), acute respiratory distress syndrome (ARDS), and death. The emergence of novel viruses with
pandemic potential poses a major threat to world health and security. In particular, the emergence of novel
coronaviruses (CoVs) of animal origin in recent decades indicates that these viruses will continue to cross
species boundaries and cause outbreaks in humans. The current outbreak of SARS-CoV-2, a highly pathogenic
CoV that causes lower respiratory tract infections and severe pneumonia, represents a severe public health
emergency and has been declared a global pandemic by the World Health Organization. SARS-CoV-2 has so
far infected nearly 3M individuals in 185 countries, resulting in over 200K deaths, with the greatest number of
confirmed cases in the U.S. While most individuals with COVID-19 report only mild illness, about 14% develop
severe disease requiring hospitalization and oxygen support, and 5% require intensive care. This has resulted
in a significant burden on healthcare systems in several countries, as well as a massive economic burden
globally. Studies have revealed that the severity of viral disease and negative health outcomes are often
associated with an overstimulated cytokine response, rather than the viral load per se. Overactivation of the
inflammatory response results in the uncontrolled release of proinflammatory cytokines, known as
hypercytokinemia, which contributes to the destruction of lung tissue, and in severe cases, leads to ARDS,
multiorgan dysfunction, and death. GP1681 moderates hypercytokinemia and may reduce the duration and
severity of many viral diseases, including COVID-19. Evaluation in mouse models has shown notable efficacy of
GP1681 in the treatment of influenza. Knowledge of the mechanism of action of GP1681 suggests that it may
be equally effective in treating COVID-19. CytoAgents has submitted an Investigational New Drug (IND)
Application to the FDA for an influenza indication and received approval to proceed with a Phase 1 study.
Additional NIH (NIAID)-funded preclinical studies are also underway in influenza models. To assess the potential
of GP1681 for use against COVID-19, the aims of this project are 1) IND-enabling toxicology studies expanding
the initial toxicology screens, as longer treatment may be needed given the typical COVID-19 disease course;
2) Pharmacokinetic (PK) analysis in a non-human primate (NHP) model; and 3) Assessment of the efficacy of
delayed GP1681 treatment in an NHP model of COVID-19, as therapy in the clinic is typically initiated at some
time after viral infection. The outcomes of this project will prepare CytoAgents for an IND application for the use
of GP1681 in the treatment of COVID-19.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><ARDS><Acute Lung Injury><Acute Pulmonary Injury><Acute Respiratory Distress><Acute Respiratory Distress Syndrome><Adult ARDS><Adult RDS><Adult Respiratory Distress Syndrome><Adverse Experience><Adverse event><African><African Green Monkey><Airway mucosa><Antigenic Determinants><Antiviral Agents><Antiviral Drugs><Antiviral Therapy><Antivirals><Binding Determinants><COVID-19><COVID-19 infection><COVID-19 outbreak><COVID-19 therapy><COVID-19 treatment><COVID-19 virus><COVID19><COVID19 infection><COVID19 outbreak><COVID19 therapy><COVID19 treatment><COVID19 virus><CV-19><CV19><Caring><Cessation of life><Chemotactic Cytokines><China><Chlorocebus aethiops><Chlorocebus sabaeus><Clinic><Clinical><CoV emergence><CoV-2><CoV2><Coronaviridae><Coronavirus><Country><Da Nang Lung><Death><Development><Disease><Disease Outbreaks><Disorder><Dose><Drug Kinetics><Dysfunction><Economic Burden><Epitopes><Evaluation><Functional disorder><Funding><Green Monkey><Grippe><Health><Health Care Systems><Healthcare><Healthcare Systems><Homologous Chemotactic Cytokines><Hospital Admission><Hospitalization><Human><IMiD><Immune modulatory therapeutic><Immune response><Immunological response><Immunomodulators><Individual><Infection><Inflammatory Response><Influenza><Influenza Virus><Innate Immunity><Intensive Care><Intercrines><Investigational Drugs><Investigational New Drug Application><Investigational New Drugs><Knowledge><Lead><Length of Stay><Lower Respiratory Tract Infection><Lower respiratory infection><Lung><Lung Parenchyma><Lung Respiratory System><Lung Tissue><MERS><MERS corona virus><MERS coronavirus><MERS coronavirus disease><MERS virus><MERS-CoV><MERS-CoV disease><Mainland China><Measurable><Measures><Mice><Mice Mammals><Middle East Respiratory Syndrome><Middle East Respiratory Syndrome CoV disease><Middle East Respiratory Syndrome Corona Virus><Middle East Respiratory Syndrome Coronavirus><Middle East Respiratory Syndrome Virus><Middle East Respiratory Syndrome coronavirus disease><Middle East Respiratory Syndrome-CoV><Middle Eastern Respiratory Syndrome><Middle Eastern Respiratory Syndrome CoV disease><Middle Eastern Respiratory Syndrome Corona virus><Middle Eastern Respiratory Syndrome Coronavirus><Middle Eastern Respiratory Syndrome Virus><Middle Eastern Respiratory Syndrome coronavirus disease><Middle Eastern Respiratory Syndrome-CoV><Modality><Modeling><Modern Man><Mucosal Inflammation><Mucositis><Murine><Mus><Mφ><NIAID><NIH><National Institute of Allergy and Infectious Disease><National Institutes of Health><Native Immunity><Natural Immunity><Non-Specific Immunity><Nonspecific Immunity><Number of Days in Hospital><O element><O2 element><Oral><Oseltamivir><Outbreaks><Outcome><Oxygen><Pathogenicity><Patients><Pb element><Pharmacokinetics><Phase 2 Clinical Trials><Phase I Study><Phase II Clinical Trials><Physiopathology><Pneumonia><Pulmonary Edema><Pulmonary Pathology><Reaction Time><Recovery><Reporting><Respiratory Mucosa><Response RT><Response Time><Risk><SARS><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS coronavirus disease><SARS-Associated Coronavirus><SARS-CO-V2><SARS-COVID-2><SARS-CoV><SARS-CoV disease><SARS-CoV-1><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV-2 outbreak><SARS-CoV-2 therapy><SARS-CoV-2 treatment><SARS-CoV2><SARS-CoV2 infection><SARS-CoV2 outbreak><SARS-Related Coronavirus><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SIS cytokines><Safety><Schedule><Security><Severe Acute Respiratory Coronavirus><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV disease><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome coronavirus disease><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 outbreak><Severe acute respiratory syndrome related corona virus 2><Severities><Severity of illness><Shock Lung><Signal Pathway><Societies><Stiff lung><Structure of parenchyma of lung><Tamiflu><Testing><Therapeutic><Time><Toxicology><Treatment Period><Treatment Protocols><Treatment Regimen><Treatment Schedule><United States National Institutes of Health><Urbanization><Vaccines><Viral><Viral Burden><Viral Diseases><Viral Load><Viral Load result><Virus><Virus Diseases><Weight><World Health><World Health Organization><Wuhan coronavirus><adaptive immunity><animal coronavirus><anti-viral agents><anti-viral compound><anti-viral drugs><anti-viral medication><anti-viral therapeutic><anti-viral therapy><anti-virals><antiviral compound><antiviral medication><antiviral therapeutic><associated symptom><base><chemoattractant cytokine><chemokine><clinical practice><co-morbid symptom><co-occuring symptom><comorbid symptom><concurrent symptom><cooccuring symptom><corona virus><corona virus disease 2019><corona virus emergence><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 outbreak><coronavirus disease 2019 therapy><coronavirus disease 2019 treatment><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 outbreak><coronavirus disease-19 virus><coronavirus emergence><coronavirus infectious disease-19><cytokine><cytokine release syndrome><cytokine storm><developmental><disease severity><drug development><efficacy analysis><efficacy assessment><efficacy evaluation><efficacy examination><emergent CoV><emergent corona virus><emergent coronavirus><emerging CoV><emerging corona virus><emerging coronavirus><evaluate efficacy><examine efficacy><hCoV19><health care><healthy volunteer><heavy metal Pb><heavy metal lead><hospital days><hospital length of stay><hospital stay><host response><immune modulating agents><immune modulating drug><immune modulating therapeutics><immune modulators><immune modulatory agents><immune modulatory drugs><immune system response><immunomodulating agents><immunomodulatory agents><immunomodulatory drugs><immunomodulatory therapeutics><immunoresponse><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><influenzavirus><lung edema><lung pathology><macrophage><mortality><mouse model><murine model><nCoV><nCoV2><new CoV><new corona virus><new coronavirus><non-human primate><nonhuman primate><novel><novel CoV><novel corona virus><novel coronavirus><novel virus><pandemic><pandemic disease><pathophysiology><phase 1 study><phase II protocol><pre-clinical development><pre-clinical study><preclinical development><preclinical study><psychomotor reaction time><public health emergency><pulmonary><respiratory><response><severe acute respiratory syndrome coronavirus 2 therapy><severe acute respiratory syndrome coronavirus 2 treatment><severe acute respiratory syndrome-CoV><stem><symptom association><symptom comorbidity><treat COVID-19><treat COVID19><treat SARS-CoV-2><treat coronavirus disease 2019><treat severe acute respiratory syndrome coronavirus 2><treatment days><treatment duration><viral infection><viral infectious disease treatment><viral resistance><virus infection><virus resistance><virus-induced disease><wet lung>