Low Dose Oral Carbon Monoxide Therapeutic for Virus-Induced Lung Injury

PROJECT SUMMARY
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.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.