e-Therapeutics PLC (LON:ETX) has unveiled the results of experimental testing on compounds for the treatment of coronavirus (COVID-19) identified using its Network-driven Drug Discovery (NDD) platform.
The AIM-listed firm said analysis of its work using models of systemic inflammatory response syndrome (SIRS) and of data sets from human cells infected with SARS-CoV-2, the virus that causes COVID-19, has revealed “a key common process which was simultaneously important to the virus and the hyperinflammatory response”, adding that the NDD platform has also predicted that inhibition of the same target, GRP94, that was effective in suppressing hyperinflammation would also be effective in disrupting the virus’s ability to replicate.
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The company also said small molecule compounds predicted by the NDD platform were tested in validated SARS-CoV-2 in vitro assays at WuXi AppTech, and in turn, these had shown “potent anti-inflammatory and anti-viral activity” against GRP94 and SARS-CoV-2.
e-Therapeutics added that this activity is also expected to be “generically applicable”, raising the prospect of using the compounds “against both existing coronaviruses that cause serious diseases such as SARS and MERS and against new emergent strains of coronavirus”.
Furthermore, the company said the compounds identified have been developed in humans for alternative indications and have an established safety profile. As a result, it said these compounds “could be rapidly deployed into clinical trials to treat patients with serious COVID-19 disease”.
The group added that it will also be feasible to develop “Novel, highly selective drugs against GRP94” and that it is continuing to work on repurposable combinations using its NDD platform and have compound combinations currently in testing with data anticipated in the first quarter of 2021 that will enhance the company’s understanding further.
“e-therapeutics’ platform has the ability to start with any biological process of relevance to disease and to identify compounds and targets that can modulate that process in a therapeutic setting. This data set is a strong validation of our platform and the network biology approach to drug discovery. e-therapeutics’ computational biology platform is capable of discovering new chemical matter, novel drug targets and uncovering new mechanisms. Here, we have deployed that capability to investigate known compounds in a novel context. We have uncovered new mechanisms that mitigate infection-induced hyperinflammation as well discovering a potent anti-viral strategy. Our findings have highlighted Bardoxolone Methyl which is already the subject of an investigator-led COVID-19 trial (NCT04494646)”, chairman and chief executive Ali Mortazavi said in a statement.
“The surprise finding of this compound’s anti-viral activity alongside its well-observed anti-inflammatory properties has led us to file a patent (GB2017631.9) which describes the use of Bardoxolone and related compounds to treat Covid-19 and other viral diseases. Previous knowledge of similar compounds has focused on the activation of the NRF2 pathway. Here, we show that both the anti-viral and anti-inflammatory properties we have observed depend on GRP94. We demonstrate that other selective GRP94 inhibitors may also be active anti-virals against a range of coronaviruses. Should Bardoxolone Methyl be progressed from its Phase 2 safety evaluation in NCT04494646 into Phase 3, we would be happy to share our anti-viral analysis with the sponsor.
“To date, no compounds with this type of potent dual activity have been reported and clinical approaches have focused on combination drug therapies using anti-inflammatory compounds such as dexamethasone combined with anti-virals such as Remdesivir. Irrespective of our findings for Bardoxolone, we believe that our project will open deeper interest in selective GRP94 inhibitors and GRP94 as a possible target for future development of therapeutics not only for COVID induced hyper-inflammation/infection but potentially other viral infections…The company intends to publish this work in a highly regarded scientific journal in the coming months”, the CEO added.
Shares in e-Therapeutics rose 8.5% to 16.6p in lunchtime trading on Tuesday.