e-Therapeutics plc COVID-19 Project Update (9286H)
December 08 2020 - 6:07AM
UK Regulatory
TIDMETX
RNS Number : 9286H
e-Therapeutics plc
08 December 2020
e-therapeutics plc
("e-therapeutics" or the "Company")
COVID-19 Project Update
Oxford, UK, 8 December 2020 - e-therapeutics plc (AIM: ETX)
announces the results of experimental testing on the compounds for
the treatment of COVID-19 identified using its proprietary
Network-driven Drug Discovery (NDD) platform.
In March 2020, the Company announced its intention to deploy its
network biology platform to identify clinical stage compounds that
either singly or in combination could be repurposed rapidly to
treat COVID-19. We chose to approach this by focussing on
therapeutic strategies that target host systems, thereby minimising
the risk of resistance and potentially being effective for the
treatment of other viral infections.
From our previous work using network models of SIRS (Systemic
inflammatory response syndrome) seen in indications such as sepsis,
we had identified a class of small molecule compounds, a mechanism
and target that was able to silence the 'cytokine storm' generated
in human blood cells by a range of inflammatory triggers. In March
2020, we undertook an in silico analysis of data sets from human
cells infected with SARS-CoV-2 and generated network models of the
cellular machinery that the virus had 'hijacked'. Analysis of both
our SIRS work and the SARS-CoV-2 networks revealed a key common
process which was simultaneously important to the virus and the
hyperinflammatory response. Our platform 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.
In May 2020, small molecule compounds predicted by our platform
were tested in validated SARS-CoV-2 in vitro assays at WuXi
AppTech. These compounds showed potent anti-inflammatory and
anti-viral activity. We report here that in vitro assays have
confirmed our in silico predictions and we have identified a clear
mechanism, target and clinical stage compounds. These compounds are
active against GRP94 and have anti-inflammatory and anti-viral
activity against Sars-CoV-2. This activity generalises to other
alpha and beta coronaviruses and is expected to be generically
applicable, raising the prospect of utility against both existing
coronaviruses that cause serious disease such as SARS and MERS and
against new emergent strains of coronavirus.
The clinical stage compounds identified have been developed in
humans for alternative indications and have an established safety
profile in man. These, and other selective compounds sharing this
target, could be rapidly deployed into clinical trials to treat
patients with serious Covid-19 disease. Given our mechanistic
insights, it would also be feasible to develop novel, highly
selective drugs against GRP94. We continue to work on repurposable
combinations using our platform and have compound combinations
currently in testing. We anticipate data that will enhance our
understanding further in Q1 2021.
Chairman & CEO Ali Mortazavi said:
" 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).
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. A presentation can be found on
our website at :
https://www.etherapeutics.co.uk/wp-content/uploads/2020/12/COVID-Project-Update-05122020.pdf
The company intends to publish this work in a highly regarded
scientific journal in the coming months."
-Ends-
For further information, please contact:
e-therapeutics plc
Ali Mortazavi, CEO Tel: +44 (0)1993 883
125
www.etherapeutics.co.uk
Numis Securities Limited Tel: +44 (0) 207 260
Freddie Barnfield/Duncan Monteith (Nominated 1000
Adviser) www.numis.com
James Black (Corporate Broking)
About e-therapeutics plc
e-therapeutics plc is an Oxford, UK-based company with a
powerful computer-based approach to drug discovery, founded on its
industry-leading expertise in network biology to fully capture
disease complexity. The Company combines network science, machine
learning, artificial intelligence, statistics and access to big
data with expertise in drug discovery and development to transform
the search for new medicines and intervention strategies.
e-therapeutics has developed an in silico laboratory that
enables the rapid screening of millions of compounds and the
identification of small sub-sets that are enriched for highly
active hits. Its proprietary platform also has novel applications
in functional genomics, being able to analyse complex genetic
datasets, provide a deep understanding of pathological mechanisms
and distil actionable insights for the discovery of novel drugs,
biomarkers and diagnostics.
e-therapeutics has deployed and validated its disease-agnostic
drug discovery platform both in house and with partners, including
Novo Nordisk, Galapagos NV and a US-based, top 5 pharmaceutical
company.
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