NeuroScientific Biopharmaceuticals Ltd (ASX: NSB) has unveiled results that suggested that the EmtinB treatment significantly reduced important biomarkers associated with severe COVID-19 and poor patient prognosis by more than 50% (vs. controls; p<0.05).
The company said the results indicate the strong therapeutic potential for EmtinB in preventing severe immune responses resulting from COVID-19 infections.
Additionally, EmtinB was shown to be safe and well- tolerated across all dose concentrations.
The biomarker studies were undertaken by leading independent research organisation Eurofins, US across 12 assay panels consisting of human primary cell-based systems (BioMAP) designed to model various human disease states. Separate tissue screening studies to assess safety in human lung tissues was performed by The Institute for Respiratory Health, Aus.
Early diagnosis and appropriate treatment are essential in reducing the morbidity and mortality of COVID-19-infected patients. Severely ill COVID-19 patients require simultaneous management of oxygenation and inflammation without compromising viral clearance. While multiple tools are available to aid oxygenation, there is unmet medical need in in immunomodulatory therapy that can adjust inflammatory immune responses and prevent fatal cytokine storms across COVID disease stages.
For the first time the team at Neuroscientific Biopharmaceuticals demonstrated in human primary cell-based systems that model complex disease biology of acute and chronic inflammation in an in vitro format (BioMAP) that its lead drug candidate EmtinB can dramatically reduce major immune biomarkers identified in COVID-19 clinical studies as indicators of severe disease and poor patient prognosis1,2,3. Decreasing these immune biomarkers indicates that EmtinB may decrease inflammatory processes that are significantly elevated during severe COVID-19 infections.
These results demonstrate the significant therapeutic utility of EmtinB and its potential modulation of inflammatory processes outside of the central nervous system. For the first time, our team have demonstrated an EmtinB-mediated effect on adaptive immune responses as evidenced by regulation of these inflammatory biomarkers,” NeuroScientific’s Managing Director, Matt Liddelow, said.
NeuroScientific’s Non-Executive Chairman, Paul Rennie, said these results demonstrate EmtinB is a true platform technology.
“Inflammation is now a well-recognised driver of disease progression in many diseases and Big Pharma Companies have a keen interest in this space. These data will demonstrate the wide range of potential clinical applications of EmtinB and therefore enhance the commercial interest in this compound”.
Among 148 clinical biomarkers tested in the human primary cell-based models, Serum Amyloid A (SAA), Interferon-gamma-inducible protein 10 (IP-10), and Eotaxin-3 (Eot3) immune markers were the most affected by EmtinB treatment, significantly reducing their expression (>50% vs. controls; p<0.05) and suggesting clinically meaningful outcomes in COVID-19 disease.
Inflammation
Inflammation is a response to a foreign organism such as viruses, bacteria, pollen, or dust particles. Ongoing studies have highlighted the role of inflammation in the progression of a variety of diseases such as cancer, atherosclerosis, asthma, and arthritis.
COVID-19 infection is accompanied by an aggressive inflammatory response with the release of a large amount of pro-inflammatory cytokines in an event known as “cytokine storm.” The ‘cytokine storm’, is where uncontrolled levels of proinflammatory cytokines (proteins released by immune cells) which cause excessive inflammation which leads to a decrease in lung function.
Proinflammatory cytokines are produced predominantly by activated macrophages and are involved in the up-regulation of inflammatory responses. Measuring proinflammatory cytokines is a ‘biomarker’ of disease and its progression.
Serum Amyloid A (SAA)
SAA is a clinical biomarker for acute phase inflammation, more commonly associated with increased risk of cardiovascular events. In COVID-19 patients, high SAA concentrations are significantly associated with more severe COVID-19 disease and an increased risk of mortality in patients.1 Therefore, regulation of SAA is important for stabilising the inflammatory processes that contribute to the severity of disease in COVID-19 patients.
Interferon-gamma-inducible protein 10 (IP-10)
Similarly to SAA, several recent publications have demonstrated IP-10 as a strong biomarker for COVID-19 disease progression and a target in preventing lung injury. Modulation of IP-10 is a suggested therapeutic strategy for treating acute respiratory distress syndrome associated with coronaviruses, including COVID-19.2
Eotaxin 3 (Eot3)
Eot3 modulates the migration of immune cells eosinophils and basophils to sites of tissue inflammation and is a clinical biomarker for airway eosinophilic inflammation in asthma.3 In severe COVID-19 patients, during the second and third phases of the disease, eosinophils participate in a maladaptive immune response and directly contribute to worsening of disease symptoms. Down-regulating Eot3, and thus triggering the blockade of eosinophil activation, may aid in improving patient outcomes.
These studies were conducted as part of NeuroScientific’s exploratory R&D program to investigate EmtinB treatment of post-COVID lung fibrosis, with the programme commencing in conjunction with the announcement of a collaborative partnership with The Institute for Respiratory Health (announced on November 20, 2020). The tissue screening studies undertaken by the Institute for Respiratory Health have been ongoing since January 2021. The biomarker study undertaken by Eurofins was conducted from June 2021 to August 2021.
Biomarker activities were annotated when two or more consecutive concentrations change in the same direction relative to vehicle controls, were outside of the significance envelope and had at least one concentration with an effect size > 20% (|log10 ratio| >0.1). The significance envelopes were calculated using historical controls (95% confidence interval). Log10ratio values have been collected by Eurofins over time (>3 years, >100 experiments) to generate a historical envelope of negative control values. The 95% significance envelope was the symmetrical upper and lower bound values of 95% of historical vehicle controls.
NeuroScientific Biopharmaceuticals has subsequently provided further information.,
HIGHLIGHTS
- Treatment with EmtinB significantly reduced SAA, IP10, Eot3 biomarkers associated with severe COVID-19 in a panel of human primary cell-based system
- Study results indicate Emtin’s therapeutic potential in preventing severe
- immune responses from COVID-19 infections
- Treatment with EmtinBwas safe and well tolerated across all dose concentrations – suggesting it is safe to administer in future work
