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ps no deaths in Scotland from Covid-19 for 19 days now as of yesterday.....something must be going on considering there's an average of 60 Covid-19 deaths each day in the UK over the last month, and Scotland had the third worst death record in the world, the first half of the year.....just an observation, but the tweet from Prof Chalmers does suggest that SFX-01's patient trials could have been up and runnung for several weeks now.;-)

Tayside Clinical Trials Unit Retweeted
James D Chalmers
@ProfJDChalmers
·
Jun 23
Thank you for @lifearc
and @Evgenpharma
for funding this important study
Mortality in severe acute respiratory infections like #COVID19 remains high. Collaborative research is the only solution @dundeeuni
@TASC_TCTU
@MereteLong
@GiamAshley
@KeirHolly
@NHSTayside
Quote Tweet
NHS Research Scotland
@NHSResearchScot
· Jun 17
Researchers from @UoDMedicine will work with drug developer @EvgenPharma to test whether the drug SFX-01 improves outcomes for #COVID19 patients. The study is being supported by @lifearc1 as part of its activities to address the need for new COVID-19 therapies. @ProfJDChalmers twitter.com/dundeeuni/stat…

Tayside Clinical Trials Unit Retweeted

James D Chalmers
@ProfJDChalmers
·
Jul 10

Research recognised as central to @NHSTayside

COVID-19 response.

550 patients enrolled across multiple studies.

So proud of our COVID research teams from the Clinical Research Centre @LesleyPeebles
@IcloLesley
@ml_crichton
and our COVID lab @MereteLong
@KeirHolly
@GiamAshley

PLANO, Texas, Aug. 03, 2020 (GLOBE NEWSWIRE) -- Reata Pharmaceuticals, Inc. (Nasdaq: RETA) (“Reata,” the “Company,” or “we”), a clinical-stage biopharmaceutical company, today announced that it will report financial results and provide an update on its development programs pre-market on August 10, 2020.

Maybe a date for the diary, no doubt there will be many Major pharma's keeping a close eye on SFX-01's development, and if there was a Strategic Investor in the pipeline which has been speculated over the last couple of months, then Reata's focus on Nrf2 activators makes them a likely suitor if they wanted to capatilise/monopolise on the Nrf2 space, and certainly have plenty of cash to make strategic investments, as per there statement 24/6/20...Gla ;-)

The huge gulf in valuation between Evgen and Reata, which was highlighted by Evgen's Executive Chairman in the latest Final results.

The gulf in valuation is truly staggering, Reata's two lead drugs ( Nrf2 activators) are more clinically advanced , but unlike SFX-01 haven't been confirmed safe ( as per their website overview, and now that SFX-01 is in phase 2/3 Covid-19 patient trials, the gap on Reata's clinical development is rapidly closing. It also appears that SFX-01 could have a wider therapeutic spectrum given that as well as its Nrf2 pathway activation , SFX-01 is also an inducer of the STAT3 signalling pathway associated with cancer and several other disease targets....and so the UPside potential opportunity here could truly be Transformational!!! :-)

15/6/20 Final Results

There remains a strong rationale for clinically testing SFX-01 in any condition that is mechanistically linked to Nrf2, as evidenced by the recent positive developments at Reata (NASDAQ: RETA). Reata is developing Nrf2 activators based on triterpenoids and with positive top-line results in pivotal trials in Friedriech's Ataxia and Alport Syndrome has a current market capitalisation of circa US$5bn. This illustrates that the fundamentals of Nrf2 activation as a therapeutic strategy are sound and SFX-01 is a potent and well tolerated Nrf2 activator; on this basis we advance with confidence in SFX-01 and believe that the main driver to ultimate success is perseverance.

....................

June 24 (Reuters) - Reata Pharmaceuticals Inc:

* REATA PHARMACEUTICALS - ANNOUNCED RECEIPT OF $350 MILLION RELATED TO CLOSING OF PREVIOUSLY ANNOUNCED STRATEGIC INVESTMENT WITH BLACKSTONE LIFE SCIENCES>

"It positions us to make strategic investments to further expand our development and commercial capabilities in preparation for the potential approval and launch of our drugs,said Manmeet S. Soni, Chief Operating Officer and Chief Financial Officer at Reata.

Coronavirus in Scotland: No new Covid-19 deaths for 19th day as 23 new cases confirmed

No new Covid-19 deaths for 19th day as 23 new cases confirmed

There have been no new deaths in Scotland overnight from Covid-19 for the nineteenth day in a row, as 23 new positive cases are announced today.

However, 15 of these new cases are in the NHS Grampian area.

First Minister Nicola Sturgeon announced that 270 patients are currently being treated for confirmed or suspected coronavirus in hospitals in Scotland - five more than yesterday.

and probably the very reason LifeArc and Dundee University selected SFX-01 from over 130 drug application candidates. ;-)

“There is evidence that Nrf2 activation can reduce the severity of acute lung injury and ARDS.

That's what I like about SFX-01's chances to treat Covid-19, although Professor Chalmers hypothesises its prevention potential, unlike many of the other drugs under evaluation, there's already documented and peer reviewed evidence that Nrf2 activation can reduce many of the severe lung conditions associated with Covid-19. Gla :-)

Covid-19 causes the development of slowly worsening lung damage called acute respiratory distress syndrome (ARDS) in around 10% of patients admitted to hospital.

When this occurs, no currently available drug can slow the progression of ARDS and patients ultimately require mechanical ventilation in intensive care until the inflammation resolves itself and the lungs begin to heal.

30% of patients with ARDS may go on to die, while the number of patients requiring ventilation for ARDS has been one of the major challenges for healthcare systems.

Finding treatments that can prevent the development of ARDS and improve patient recovery is therefore one of the top priorities for Covid-19 research.

James Chalmers, British Lung Foundation Professor of Respiratory Research at the University said: “SFX-01 is an anti-inflammatory medication that we believe may have the potential to reduce some of the worst outcomes of Covid-10.

“The body defends itself against inflammatory and oxidative stress by increasing levels of chemical called Nrf2.

“SFX-01 activates the Nrf2 system and puts it into overdrive to enhance defences against inflammatory damage.

“There is evidence that Nrf2 activation can reduce the severity of acute lung injury and ARDS.

“As such, we hypothesise that early treatment with an Nrf2 activator in patients hospitalised with COVID-19 may prevent deterioration and help to preserve precious ICU resources in the context of the pandemic.

Courtesy of Oranolio on advfn...Gla ;-)

From Evgen, I emailed them again about the covid-19 trial and again they responded very promptly....

The trial is being run by the University of Dundee. The study was expected to begin enrolment last month, in July.

Could've started on the 1st July.

19 days in a row!!! ;-)

Scottish numbers: 4 August 2020

23 new confirmed cases of COVID-19; this is 0.9% of newly tested individuals.
0 new reported death(s) of people who have tested positive.
4 people were in intensive care last night with confirmed COVID-19.
270 people were in hospital with confirmed COVID-19.
5,879 new tests for COVID-19 that reported results.

Highlights

The host inflammatory response is a crucial determinant of disease outcome and correlates with disease severity in SARS-CoV-2-induced infection, for which there is no treatment to date.

Activation of transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) promotes resolution of inflammation and, in parallel, restores cellular redox and protein homeostasis, and facilitates tissue repair.

NRF2 can be activated by pharmacological inducers that target Kelch-like ECH-associated protein 1 (KEAP1), the principal negative regulator of NRF2.

The available information on pharmacokinetics, pharmacodynamics, safety, and efficacy for the NRF2 activators sulforaphane and bardoxolone methyl (currently in advanced clinical trials for other disease indications) in humans makes them excellent candidates for testing in randomized clinical trials in COVID-19.

https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(20)30165-6?sf236269648=1

A.T.D-K. is a member of the Scientific Advisory Board of Evgen Pharma and a consultant for Aclipse Therapeutics and Vividion Therapeutics.

20 May 2020

News

Roche enters $135m drug discovery deal with Vividion Therapeutics

https://www.pharmaceutical-technology.com/news/roche-vividion-therapeutics-deal/

Published June 2020

KEAP1, a cysteine-based sensor and a drug target for the prevention and treatment of chronic disease

Abstract

Redox imbalance and persistent inflammation are the underlying causes of most chronic diseases. Mammalian cells have evolved elaborate mechanisms for restoring redox homeostasis and resolving acute inflammatory responses. One prominent mechanism is that of inducing the expression of antioxidant, anti-inflammatory and other cytoprotective proteins, while also suppressing the production of pro-inflammatory mediators, through the activation of transcription factor nuclear factor-erythroid 2 p45-related factor 2 (NRF2). At homeostatic conditions, NRF2 is a short-lived protein, which avidly binds to Kelch-like ECH-associated protein 1 (KEAP1). KEAP1 functions as (i) a substrate adaptor for a Cullin 3 (CUL3)-based E3 ubiquitin ligase that targets NRF2 for ubiquitination and proteasomal degradation, and (ii) a cysteine-based sensor for a myriad of physiological and pharmacological NRF2 activators. Here, we review the intricate molecular mechanisms by which KEAP1 senses electrophiles and oxidants. Chemical modification of specific cysteine sensors of KEAP1 results in loss of NRF2-repressor function and alterations in the expression of NRF2-target genes that encode large networks of diverse proteins, which collectively restore redox balance and resolve inflammation, thus ensuring a comprehensive cytoprotection. We focus on the cyclic cyanoenones, the most potent NRF2 activators, some of which are currently in clinical trials for various pathologies characterized by redox imbalance and inflammation.

Keywords: KEAP1; NRF2; anti-inflammatory; antioxidant; cysteine; redox.
Conflict of interest statement

A.T.D-K. is a member of the Scientific Advisory Board of Evgen Pharma and a consultant for Aclipse Therapeutics and Vividion Therapeutics.

https://pubmed.ncbi.nlm.nih.gov/32574549/

What's going on in Scotland!!!??? ;-)

There have been no coronavirus deaths in Scotland for the 18th day in a row, Nicola Sturgeon said.

The First Minister gave the latest figures at the Scottish Government's daily coronavirus briefing in Edinburgh.

A total of 2,491 patients have died in Scotland after testing positive for Covid-19.

Ms Sturgeon said 18,694 people have tested positive for the virus, up by 18 from 18,676 the day before.

She said 11 of these new cases were in the Grampian area, though she could not say if these were linked to the outbreak in Aberdeen.

There were 265 people in hospital with confirmed Covid-19, no change on the previous day.

Of these, three were in intensive care, no change on the previous total.

Cell  Press

@CellPressNews

·

1 Aug

Pharmacological activation of NRF2 could be a way to combat Acute respiratory distress syndrome #ARDS caused by #SARSCoV2. Albena Dinkova-Kostova

@UoDMedicine

, Antonio Cuadrado

@UAM_Madrid

and colleagues outline their strategy.

@TrendsinPharma

https://bit.ly/30h0iJk

SFX-01 or not, something is going on in Scotland....BBC TV news last night have reported there were an average of 56 Covid-19 deaths in the UK every day throughout July, yet Scotland have reported no deaths 17 days in a row, yet Scotland had the 3rd worst death record in Europe the first half of this year!!!??...Gla :-)

Coincidence or the SFX-01 effect??? :-)

BBC news have reported there were an average of 56 Covid-19 deaths every day throughout July, yet Scotland have reported no deaths 17 days in a row...Gla :-)

There have been no new coronavirus deaths registered in Scotland for a seventeenth day, as 31 new positive cases are announced today.

The total number of positive cases is now 18,676, according to the latest Scottish Government released figures.

Scottish numbers:

2 August 2020

31 new confirmed cases of COVID-19; this is 1.1%of newly tested individuals

0 new reported death(s) of people who have tested positive (noting that Register Offices are now generally closed at weekends)

3 people were in intensive care last night with confirmed COVID-19

265 people were in hospital with confirmed COVID-19

8,243 new tests for COVID-19 that reported results

Coronavirus (COVID-19): daily data for Scotland

Published: 2 Aug 2020

Directorate:Chief Medical Officer DirectorateCoronavirus in Scotland, Health and social care

This is updated each day to provide the latest available data on COVID-19 in Scotland.

Scottish numbers: 2 August 202031 new confirmed cases of COVID-19; this is 1.1%of newly tested individuals0 new reported death(s) of people who have tested positive (noting that Register Offices are now generally closed at weekends)3 people were in intensive care last night with confirmed COVID-19265 people were in hospital with confirmed COVID-198,243 new tests for COVID-19 that reported results

RESULTS SFX-01 reduced MFE of both ER+ primary and metastatic patient samples. Both tamoxifen and fulvestrant increased MFE and ALDH activity of PDX tumors, which was reversed by combination with SFX-01. SFX-01 significantly reduced tumor initiating cell frequency in secondary transplants at limiting dilution and reduced the formation of spontaneous lung micrometastases by PDX tumors in mice. Mechanistically, we establish that both tamoxifen and fulvestrant induce STAT3 phosphorylation. SFX-01 suppressed phospho-STAT3 and SFN directly bound STAT3 in patient and PDX samples. Analysis of ALDH+ cells from endocrine-resistant patient samples revealed activation of STAT3 target genes MUC1 and OSMR, which were inhibited by SFX-01 in patient samples. Increased expression of these genes after 3 months’ endocrine treatment of ER+ patients (n=68) predicted poor prognosis.

CONCLUSIONS Our data establish the importance of STAT3 signaling in CSC-mediated resistance to endocrine therapy and the potential of SFX-01 for improving clinical outcomes in ER+ breast cancer.

https://www.biorxiv.org/content/10.1101/2020.02.03.932194v1