In the search for therapeutics that are effective against Covid-19, four drugs have been tried with disappointing results. Remdesivir, hydroxychloroquine, lopinavir, and interferon regimens appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay, according to a recent World Health Organization report.
There is some good news, Regeneron drug antibody cocktail, administered early, can enable patients who are early in the disease state to mount a more effective immune response to fight off the virus. It provides a therapeutic substitute for the naturally occurring immune response. In other words, patients who get their drug can clear the virus quicker. It will allow them to have less prolonged symptoms. (think of a drug like Tamiflu). However, if the window is missed, patients may face many complications.
Approaches from smaller companies such as FSD Pharma and Aqualung Therapeutics is focused on preventing and reducing ongoing virus-induced inflammation and preventing the ventilator-induced cytokine storm of acute respiratory disease (ARDS). These drug aims to dampen the cytokine storm and allow less time on the ventilator and fewer days in the hospital. Q BioMed’s drug offers lung protection from the virus by reduces lung endothelial vascular leakage, inflammation and cell death that occurs during severe viral infection.
Below is a brief description of small biotech firms along with information on their approaches:
FSD Pharma
CEO: Dr. Raza Bokhari
STATUS: Trials have begun with dosing in October 2020
FSD Pharma announced recently that the Food and Drug Administration (FDA) authorized the initiation of a Phase 2 study for the use of FSD201 (ultramicronized palmitoylethanolamide, or ultramicronized PEA) to treat COVID-19, the disease caused by the SARS-CoV-2 virus. The company is expected to start dosing patients this month.
FSD201 may have the potential to address the over-exuberant inflammatory response characterized by COVID-19 infection that may lead to a cytokine storm and ultimately death. Micro PEA was promoted between 1969 and 1979 as a treatment for influenza and the common cold. Clinical trials conducted at the time showed PEA was an effective prophylactic in respiratory infection, with no registered side effects. According to scientists behind the research, it could act as a quick therapeutic answer for flu epidemics.
CEO Dr. Raza Bokhari emphasized that FSD does not claim cannabinoids, synthetic or plant-based, is an alternative for COVID-19 treatment. FSD-201 modulates the endocannabinoid system as “a naturally occurring fatty acid” by targeting CB2 receptors, which are believed to affect pain and inflammation in humans.
Q BioMed
CEO: Denis Corin
STATUS: Phase 1 human trials to begin Feb 2021
Q BioMed Inc. and its technology partner, Mannin Research, are working on a novel virus-agnostic and host-directed therapeutic called MAN-19. The research is being supported in part by funding from the Canadian and German governments under various R&D incentive and COVID-19 response initiatives. The Phase 1 clinical trial is slated to begin patient enrollment in February 2021. Mannin’s core R&D program is based on the Angiopoeitin-Tie2 Mechanism of Action. Mannin’s small molecules and its biologic therapeutic target the endothelium of the patient, stabilizing endothelial barrier integrity by activating Tie2, which in turn reduces lung endothelial vascular leakage, inflammation and cell death that occurs during severe viral infection. This is a novel and promising therapeutic strategy as its mechanism of action is independent of viral replication, but instead focuses on endothelium of the host as the critical target for treatment intervention.
Human observational and genetic studies, as well as animal models of endothelial dysfunction collectively suggest that by targeting Tie2 receptor, MAN-19 may be effective in the treatment of a number of complications associated with viral infections such as COVID-19 and the seasonal flu. Therapeutics based on the Mannin platform have the potential to offer clinicians an intervention to rapidly stabilize the patient’s vascular endothelium in hospital settings, such as the Intensive Care Unit (ICU), to prevent vascular leakage, pulmonary pathology, and acute respiratory distress syndrome (ARDS). Such an intervention could improve outcomes in the current COVID-19 pandemic around the world.
Aqualung Therapeutics
CEO: Dr. Joe G.N. “Skip” Garcia
STATUS: IND submitted; clinical trials expected for 2021
One critical area where the NHI and BARDA has been quickly working with researchers is developing a possible therapy for acute respiratory distress syndrome (ARDS) – one of the more concerning complications caused by COVID-19. ARDS is a type of respiratory failure characterized by inflammation of the lungs. Researchers found COVID-19 patients had a high death rate if they also developed ARDS, that has a mortality rate of 35-40%, that occurs in patients with severe lung inflammation, low levels of oxygen in the blood (hypoxemia) and respiratory failure that requires mechanical ventilation as a life-saving intervention but which also contributes to lung inflammation and ARDS mortality. In such cases, treatment requires placement on a ventilator and mechanical ventilation for respiratory failure. There are no FDA–approved treatments for ARDS or for ARDS-inducing stimuli such as COVID-19.
Aqualung Therapeutics is developing an anti-inflammatory monoclonal antibody, ALT-100 to treat serious “unchecked inflammation’. The initial application for ALT-100 aims to reduce the mortality of Acute Respiratory Distress Syndrome (ARDS) and Ventilator-Induced Lung Injury (VILI). This offers a potential option in the treatment of COVID-19, which causes severe pneumonia and respiratory failure and can be compounded by mechanical ventilation, resulting in multi-organ failure and death. The Company is actively engaged with government agencies such as the NIH & the DoD for additional funding opportunities and has begun required testing as part of the Investigational New Drug (IND) regulatory package for the FDA.