There is an urgent need for the development of new approaches to treat patients suffering from pulmonary injury from viral infections, as demonstrated by the severe impact of COVID-19, which is a global pandemic that, at the time of writing, is estimated have impacted approximately 50 million people in the United States, leading to morbidity, substantial hospital and intensive care utilization, and mortality. In multiple preclinical studies, we and others have defined the therapeutic potential of low dose exogenous carbon monoxide (CO) in acute lung injury, including in virus-induced pulmonary injury, by reducing inflammation and promoting viral clearance. To date, inhaled CO gas (iCO) and CO bound to carrier molecules (CORMs) have been the modalities of choice in the majority of animal and in all the clinical studies, and the safety and tolerability of CO has been demonstrated in 23 successful Phase 1 and 2 clinical studies, including in patients with pulmonary conditions such as ARDS and COPD. However, iCO and CORMS are not expected to be pharmaceutically acceptable and viable therapeutic options in COVID patients due to, for iCO, the risk of accidental inhalation exposure from the presence of compressed CO gas cylinders and imprecise dosing, especially in COVID-19 patients that have limited and variable respiratory function, and, for CORMs, problematic release kinetics and toxicological concerns with carrier molecules. The objective of the proposed project is to investigate HBI-002, a novel oral low dose CO drug product that enables the use of low dose CO in viral infections associated with acute pulmonary injury, such as COVID-19. HBI-002 is an oral liquid drug product containing CO. An IND is in place for HBI-002, with a Phase 1 clinical trial in healthy volunteers planned in 2022. The next step in development is to demonstrate that HBI-002 is effective in clinically relevant animal models of viral acute lung injury as has been shown with other forms of CO and to better understand the potential mechanism(s) of action. Based upon the substantial literature of CO in acute lung injury and our and others findings in virus-induced lung injury, our central hypothesis that will be tested in this project is: HBI-002 modulates the immune response to regulate inflammation and improve viral clearance in experimental models of virally induced lung injury sufficiently to warrant a Phase 2 clinical trial.
Public Health Relevance Statement: PROJECT NARRATIVE This proposal is intended to support research evaluating whether HBI-002, an oral low dose carbon monoxide (CO) therapeutic, can improve outcomes in animal models of acute pulmonary disease associated with viral infections, such as in COVID-19 and severe influenza. If successful, the project will provide proof-of-concept for further development of HBI-002 in treating severe viral infections from COVID-19 and other potential viral pandemics as a promising therapeutic to improve outcomes in these devastating conditions.
Project Terms: Sickle Cell Anemia; Hb SS disease; HbSS disease; Hemoglobin S Disease; Hemoglobin sickle cell disease; Hemoglobin sickle cell disorder; sickle cell disease; sickle cell disorder; sickle disease; sicklemia; Animals; Antiviral Agents; Antiviral Drugs; Antivirals; anti-viral agents; anti-viral compound; anti-viral drugs; anti-viral medication; anti-viral therapeutic; anti-virals; antiviral compound; antiviral medication; antiviral therapeutic; Award; Biological Availability; Bioavailability; Biologic Availability; Physiologic Availability; Carbon Monoxide; Cells; Cell Body; Clinical Research; Clinical Study; Clinical Trials; Dexamethasone; Canis familiaris; Canine Species; Dogs; Dogs Mammals; canine; domestic dog; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Economics; Gases; Goals; Mesocricetus auratus; Golden Hamsters; Golden Syrian Hamsters; Syrian Hamsters; Hemoglobin concentration result; hemoglobin level; Hemoglobin; Hospitals; Human; Modern Man; Infection; Inflammation; Influenza; Grippe; Intensive Care Units; Kinetics; Laboratories; Literature; Lung; Lung Respiratory System; pulmonary; Lung diseases; Pulmonary Diseases; Pulmonary Disorder; disease of the lung; disorder of the lung; lung disorder; Methods; Morbidity - disease rate; Morbidity; mortality; Mus; Mice; Mice Mammals; Murine; Persons; Pathology; Patients; Common Rat Strains; Rat; Rats Mammals; Rattus; Research; Investigators; Researchers; Research Personnel; Research Support; ARDS; Acute Respiratory Distress; Adult ARDS; Adult RDS; Adult Respiratory Distress Syndrome; Da Nang Lung; Shock Lung; Stiff lung; wet lung; Acute Respiratory Distress Syndrome; respiratory function; Respiratory physiology; Risk; Safety; Seasons; Taxes; Testing; Time; Toxicology; Translations; United States; Vaccination; Virus Diseases; Viral Diseases; viral infection; virus infection; virus-induced disease; Virus; Writing; Intensive Care; Experimental Models; Injury; injuries; base; human subject; improved; Acute; Chronic; Phase; Physiological; Physiologic; Acute Pulmonary Injury; Acute Lung Injury; Lung damage; pulmonary damage; pulmonary injury; pulmonary tissue damage; pulmonary tissue injury; lung injury; Phase 2 Clinical Trials; phase II protocol; Phase II Clinical Trials; Immunological response; host response; immune system response; immunoresponse; Immune response; Therapeutic; fluid; liquid; Liquid substance; Inflammatory; Life; Viral Burden; Viral Load; Viral Load result; Oral; Viral; Inhalation Exposure; meetings; experience; Animal Models and Related Studies; model of animal; model organism; Animal Model; Toxicities; Toxic effect; novel; Modality; Modeling; viral respiratory infection; Viral Respiratory Tract Infection; Experimental Animal Model; Phase I Clinical Trials; Early-Stage Clinical Trials; Phase 1 Clinical Trials; phase I protocol; Influenza A virus; Influenza A; Influenza Viruses Type A; Influenzavirus A; Orthomyxovirus Type A; Type A Influenza; Inflammatory Response; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; Pharmacologic Substance; Therapeutic Uses; preventing; prevent; Dose; Data; in vivo; research clinical testing; Clinical Evaluation; Clinical Testing; clinical test; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Tissue Model; Development; developmental; Influenza A Virus, H1N1 Subtype; H1N1; H1N1 Virus; pandemic disease; pandemic; pre-clinical; preclinical; preclinical study; pre-clinical study; novel strategies; new approaches; novel approaches; novel strategy; Treatment Efficacy; intervention efficacy; therapeutic efficacy; therapy efficacy; innovation; innovate; innovative; clinically relevant; clinical relevance; novel therapeutics; new drug treatments; new drugs; new therapeutics; new therapy; next generation therapeutics; novel drug treatments; novel drugs; novel therapy; healthy volunteer; therapeutic development; therapeutic agent development; treatment strategy; preclinical efficacy; pre-clinical efficacy; phase 2 study; phase II study; Secure; Pulmonary Inflammation; Lung Inflammation; Pneumonitis; Formulation; improved outcome; Innate Immune Response; Inhalation; Inhaling; Lung infections; pulmonary infections; COVID-19; COVID19; CV-19; CV19; corona virus disease 2019; coronavirus disease 2019; coronavirus disease-19; coronavirus infectious disease-19; 2019-nCoV; 2019 novel corona virus; 2019 novel coronavirus; COVID-19 virus; COVID19 virus; CoV-2; CoV2; SARS corona virus 2; SARS-CO-V2; SARS-COVID-2; SARS-CoV-2; SARS-CoV2; SARS-associated corona virus 2; SARS-associated coronavirus 2; SARS-coronavirus-2; SARS-related corona virus 2; SARS-related coronavirus 2; SARSCoV2; 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 CoV 2; 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 related corona virus 2; Wuhan coronavirus; coronavirus disease 2019 virus; coronavirus disease-19 virus; hCoV19; nCoV2; COVID-19 treatment; COVID-19 therapy; COVID19 therapy; COVID19 treatment; SARS-CoV-2 therapy; SARS-CoV-2 treatment; coronavirus disease 2019 therapy; coronavirus disease 2019 treatment; severe acute respiratory syndrome coronavirus 2 therapy; severe acute respiratory syndrome coronavirus 2 treatment; treat COVID-19; treat COVID19; treat SARS-CoV-2; treat coronavirus disease 2019; treat severe acute respiratory syndrome coronavirus 2; COVID-19 patient; COVID infected patient; COVID patient; COVID positive patient; COVID-19 infected patient; COVID-19 positive patient; COVID19 patient; COVID19 positive patient; SARS-CoV-2 infected patient; 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developing anti-viral drug; developing anti-viral therapeutic; developing anti-viral therapy; developing antiviral agent; developing antiviral drug; developing antiviral therapeutic; developing antiviral therapy
