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Assessment and interim analysis on the first 100 patients recruited to SFX-01's Covid/ARDS trial could now be underway, and so everything firmly crossed for positive data from Huw and the DSMB which would be transformational for all concerned.

SFX-01 was selected by Lifearc and University of Dundee from over 130 drug applications and so they obviously have high hopes for a successful outcome given SFX-01's potency and activation over the key NRF2 pathway, associated with multiple inflammoratory diseases and respiratory illness, and the recent exciting developments made by Prof Chalmers and his lab in understanding Neutrophil dysfunction could be highly significant in adding weight to SFX-01's chances of success, with the the trials exploratory objectives focused on the measurment of NRF2 activity, Neutrophil function, il-6, il-1 betea and TNF, all of which are well document research targets for ARDS/Covid, and all of which are well documented whereby Sulforaphane plays a part and has a signiificant effect.

Sulforaphane significantly inhibits ARDS in rabbits and plays a protective role in ARDS through upregulating Nrf2, and so let's hope this translates to humans.....EVG will move BIG on positive data. Gla ;-)

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COVID-19 and Neutrophils: The Relationship between Hyperinflammation and Neutrophil Extracellular Traps

4/12/20

The interaction hypothesis between neutrophil and hyperinflammation in COVID-19. After the host-viral interaction, the virus signaling leads to a cascade of interactions between the virus recognition mechanism, neutrophil activation, and inflammatory stimuli. The NETosis process can protect the host during the virus response or exacerbate lung hyperinflammation in COVID-19 patients. The figure is made with BioRender (hxxps://app.biorender.com/). Abbreviations: SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; PAMP: pathogen-associated molecular pattern; DAMP: danger-associated molecular pattern; TNF: tumor necrosis factor; IL-6: interleukin-6; IL-1: interleukin-1; IL-8: interleukin-8; ROS: reactive oxygen species; NE: neutrophil elastase; MPO: myeloperoxidase.

htTps://www.hindawi.com/journals/mi/2020/8829674/

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

Exploratory objectives

Analysis of Nrf2 pathway activity in isolated peripheral blood mononuclear cells

Neutrophil functional studies in isolated cells

Measurement of interleukin-6, interleukin-1 beta and TNF-alpha in blood

https://star-covid19.com/

Yep, the first 100 patients could be recruited by now ontarget, and so very exciting times as we await an Update from Huw on the DSMB's assessment, the greenlight will be a huge endorsement and any positive detail from Huw could be transformational.

We also have multiple potential newsflow stacking UP from the rest of the pipeline which could add significant value , and with the fund raise done and dusted by early March we should see a raft of TR1 disclosures from existing Major Shareholders but also from the new Major investors that Huw has already welcomed in his last UPdate which could be very interesting ( i wonder if Jim Mellon has taken a chunk, now that would be big news given his following, and certainly would speak volumes).

We should also see a flood of new pi's thereafter, attracted by a fully funded Bio for the forseeable, with undoubted transformational prospects and potential with multiple shots on multiple targets. Gla holders......Evgen could be the Star share of 2021 if all goes to plan....On and UP!!! ;-)

"understanding the function of neutrophils may be helpful in the treatment of ARDS."

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"Exciting developments in understanding inflammation and treating neutrophil dysfunction"

Abstract

Acute respiratory distress syndrome (ARDS) is difficult to treat and is associated with a high mortality rate. The most severe form of coronavirus disease 2019 (COVID-19) also leads to life-threatening ARDS.

Neutrophil counts are positively correlated with disease severity in ARDS.

Neutrophil activation not only plays a significant role in immune defense against infections, but also causes tissue damage and leads to inflammatory diseases.

Activated neutrophils rapidly migrate to inflamed lung tissue, releasing toxic granular contents and generating neutrophil extracellular traps.

In the last few decades, it has become apparent that neutrophils occupy a central role in ARDS pathology. In this review, we summarize the neutrophil inflammatory responses and their relationships to ARDS.

According to the current literature, understanding the function of neutrophils may be helpful in the treatment of ARDS.

Keywords

ARDS Neutrophil Inflammation

https://www.sciencedirect.com/science/article/pii/S2319417020301499

All in good time mrshoubs, its certainly got kingoaf rattled...ho ho ho Gl ;-)

25.000 

"Exciting developments in understanding inflammation and treating neutrophil dysfunction reviewed" ....the exciting developments made in Prof Chalmers lab could be highly significant for SFX-01 for Covid/ARDS and the reason why he has joined Evgen's Scientific Advisory Board at this pivotal stage as we await the assessment by the DSMB on the first 100 patients recruited. ....Gla Holders....Very exciting times for hose invested ;-)

ps the Smart Money is flooding in...;-)

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29/1/21

James D Chalmers
@ProfJDChalmers
·
51m
New in @ERSpublications

Neutrophil dysfunction in bronchiectasis: an emerging role for immunometabolism

Exciting developments in understanding inflammation and treating neutrophil dysfunction reviewed by the brilliant @GiamAshley

@Shoemelia
@dundeeuni
@UoDMedicine

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

SFX-01 Phase 2b / phase 3 Covid/ARDS patient Trial.

Exploratory objectives

Analysis of Nrf2 pathway activity in isolated peripheral blood mononuclear cells

Neutrophil functional studies in isolated cells

Measurement of interleukin-6, interleukin-1 beta and TNF-alpha in blood

https://star-covid19.com/

Evgen Pharma raised £10m with up to £1.0m possible through an Open Offer to
fund/progress SFX-01 to key valuation inflection points that will provide a cash
runway until at least mid-2023.

LifeArc’s selection of SFX-01 and funding of a 300- patient Phase II/III trial in Acute Respiratory Distress Syndrome (ARDS), including COVID-19 patients, is a significant endorsement of SFX-01’s potential value, with near-term interim safety and futility data analysis expected in Q2 2021.

Additionally, Evgen should have potentially three Phase II-ready programmes by
year-end 2021, a platform technology that can translate into further investigatorled studies and a royalty stream from the application of Sulforadex as a delivery vehicle in non-pharma applications (up to $10.5m milestones plus royalties).

With this number of shots on goal, any one of which would be significant, we increase our SOTP rNPV-based target price to 29p with a bear/bull scenario of 15-52p.

Placing raised £10m with Open Offer (up to £1m) by way of the issue of up to 137.5m
shares at 8p, representing 50.0% of the enlarged equity.

Net funds will be used for

(i) additional preclinical studies,

(ii) a glioma clinical trial,

(iii) formulation and scale-up manufacturing for SFX-01 and

(iv) work to file an IND for SFX-01 in the US.

This will provide a cash runway to mid-2023 and through multiple valuation inflection points.

Novel molecule that has been shown to directly modulate at least three unrelated
mechanistic targets; Nrf2, STAT3 and more recently SHP2, resulting in Evgen targeting four diseases in cancer and inflammation, all with high unmet clinical needs.

Acute Respiratory Distress Syndrome (ARDS) +/- COVID-19. An interim safety/futility
analysis for the Phase II/III STAR trial is expected in Q2 2021, based on the first 100 patients, 89 of whom are enrolled. This should be a meaningful valuation inflection point.

Pre-clinical data updates in H1 2021 should provide the clarity for Evgen’s positioning of SFX-01 in breast cancer (eg. CDK4/6 resistant tumours), glioma (brain cancer) and a third undisclosed oncology indication and the evidence to partners for monetisation events.

Not without risk, but multiple shots on goal provide investors substantial upside
potential, given the number of opportunities that exist for monetising SFX-01 and
Sulforadex.

Average licence deal values within the areas of focus have generated upfront
payments and milestones of $11-35m and up to $325m, respectively, in addition to longterm royalty streams.

Forecasts and valuation. We introduce new forecasts for 2021 and 2022 to reflect the costs of the CMC manufacturing scale-up activities, with year-end FY 2021 cash of c.£4.1m and a cash runway extending to year-end 2022.

We raise our SOTP rNPV target price to 29p to reflect the potential value in ARDS, Glioblastoma and Juvenescence.

Unlike kingoaf and co Finncap are looking rather bullish on Evgen's prospects and potential, and good news from the assessment of the DSMB on the first 100 patients recruited to the Covid/ARDS trial will see a mad dash for shares, including all of the placing shares, the majority of which will be tightly held imho...The Smart Money is piling in....Gla Holders ;-)

Lol....looks like kingoaf and Superboy atre worried about the sp heading UPwards....ha ha ha ha Gla Holders....On and UP!!! ;-)

 0

Prof Chalmers, Lead investigator of SFX-01 Covid/ARDS patient trials , has made exciting new developments with his team in understanding Neutrophil dysfunction, and has just joined Evgen as a Scientific advisor....Bring it On!!! :-)

In contrast, in the case of East Asia, Thailand has the highest at 19.9 per 1,000 individuals while it is just 8 and 5.4 per 1,000 individuals in Malaysia and South Korea, respectively.

“Even the lowest AAT protein deficiency level seen in the population in the U.S. and Poland is much more than the highest level seen in East Asia. This explains why the variant with the D614G mutation spread widely in Europe and North America and not in East Asia,” concludes Dr. Majumdar.

 0

UPDATED: 07 FEBRUARY 2021 22:44 IST

    

A study found that the variant with the D614G mutation introduced an additional cleavage site on the ACE-2 receptor for the SARS-CoV-2 virus to gain entry into cells

Kalyani-based scientists have found the biological mechanism behind the significantly faster spread of a variant with D614G mutation in Europe and North America but not in East Asia.

The variant with the D614G mutation seeded large outbreaks in Europe in early 2020 and subsequently dominated the outbreaks in North America, thereby largely replacing previously circulating lineages. The variant also spread worldwide.

A team led by Dr. Nidhan K. Biswas and Dr. Partha Majumdar from the National Institute of Biomedical Genomics, Kalyani found that the variant with the D614G mutation introduced an additional cleavage site on the ACE-2 receptor for the SARS-CoV-2 virus to gain entry into cells.

However, the presence of an additional cleavage site alone does not automatically lead to better efficiency in entering the cells. For the virus to enter the cells more efficiently, the additional cleavage site has to be opened. “The site is opened by a human protein called the neutrophil elastase. This protein is available in plenty in the lungs,” says Dr. Majumdar. “When the level of neutrophil elastase is high in an individual, the additional entry point created by the mutation opens up in a larger number of cells thus allowing more cells to be infected. Thus, the variant with the D614G mutation is able to spread better from one infected individual to another.
 
But an excess amount of the protein neutrophil elastase can damage the lung tissue. Hence, the amount of neutrophil elastase produced is naturally kept under check by a protein called AAT (alpha1-antitrypsin). In other words, the AAT protein inhibits neutrophil elastase production.

However, some naturally-occurring mutations in the AAT-producing gene result in deficiency of the AAT protein, explains Dr. Majumdar. The AAT protein deficiency thus results in a higher level of neutrophil elastase and hence enhanced ability of the virus to infect human cells and spread among people.

“Compared with Asians, we found a large proportion of Caucasians in European countries and North America carry natural mutations in the gene that leads to deficiency in AAT production,” says Dr. Majumdar. “This is the reason why the variant spread widely in Europe and North America but not in Asia.” The results of the study are published in the journal Infection, Genetics and Evolution.

According to the paper, at 18.7 per 1,000 individuals, the AAT deficiency is the least in Poland while in Portugal as many as 75.9 per 1,000 individuals have AAT deficiency. Spain has the second highest deficiency of AAT protein at 67.3 per 1,000 individuals while it is 51.9 per 1,000 individuals in the case of France. Canada and the U.S. have 32.1 and 29 per 1,000 individuals with the protein deficiency, res

Anyways, why would SFX-01's Lead Investigator, the highly respected and renowned Prof Chalmers take up a position on Evgen's Scienctifc Advisory Board, only days or a few weeks before the DSMB assessment on the first 100 patients???? Why now?????? Gla :)

Very interesting that Prof Chalmers has posted the above today...I wonder if looks in here and Advfn now he's on the Evgen Scientific Advisory Board!!!??? Gla :-)

James D Chalmers Retweeted

Neutrophil2021

@neutrophil2021

The program for #Neutrophil2021 is now finalised and live on our website https://theneutrophil.com Further details for registration & flash talks coming soon!

Quote Tweet

Neutrophil2021

@neutrophil2021

· 19 Jan

We are pleased to announce that Neutrophil 2021 is happening online. See announcement

#Neutrophil2021 "zoomed in" 31 May - 1 June 21, RT & follow for further announcements

ps great news from aTyr Pharma that further validates SFX-01's potential.....Exciting times!!! ;-)

"Exciting developments in understanding inflammation and treating neutrophil dysfunction reviewed" ....the exciting developments made in Prof Chalmers lab could be highly significant for SFX-01 for Covid/ARDS imho...and not too long before we find out....Gla ;-)

ps the Smart Money is flooding in...;-)

More on those neutrophils , that were highlighted by Prof Chalmers on Friday. Gla :-)

.......

November 2020

An opportunity has arisen for a Research Technician to support our internationally leading lung Infection laboratory at the University of Dundee. The group studies a range of lung infections including COVID-19.

You will be expected to provide high quality technical assistance to Professor Chalmers and the other members of the research team. Core tasks will include processing biological samples, isolating inflammatory cells such as neutrophils and measuring response to treatments using techniques such as ELISA and flow cytometry.

You will support the principal investigator, post-docs and PhD students as part of a multidisciplinary team, performing laboratory research to a high standard, organising study data and supervising undergraduates.

You will work collaboratively with team members to support multiple ongoing research studies including two national COVID-19 studies STOP-COVID (hTtps://stop-covid19.org.uk/) and STAR-COVID hTtps://www.lifearc.org/funding/covid-19-funding-2/sfx-01/

https://www.mendeley.com/careers/job/research-technician-1513565

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Drugs targeting neutrophils could reduce ARDS in severe COVID-19

Download PDF Copy

Dr. Liji Thomas, MDBy Dr. Liji Thomas, MDNov 15 2020

Coronavirus disease 2019 (COVID-19) cases continue to rise across the globe. Over 54.3 million people have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the causative agent of COVID-19 – and 1.31 million have lost their lives.

Scientists in Taiwan recently published a report on their use of anti-neutrophil strategies to treat acute respiratory distress syndrome (ARDS) – a life-threatening condition that can arise in critical COVID-19 cases – in the journal Frontiers in Pediatrics.

https://www.news-medical.net/news/20201115/Drugs-targeting-neutrophils-could-reduce-ARDS-in-severe-COVID-19.aspx

Giam Ashley

29/1/21

James D Chalmers
@ProfJDChalmers
·
51m
New in @ERSpublications

Neutrophil dysfunction in bronchiectasis: an emerging role for immunometabolism

Exciting developments in understanding inflammation and treating neutrophil dysfunction reviewed by the brilliant @GiamAshley

@Shoemelia
@dundeeuni
@UoDMedicine

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

SFX-01 Phase 2b / phase 3 Covid/ARDS patient Trial.

Exploratory objectives

Analysis of Nrf2 pathway activity in isolated peripheral blood mononuclear cells

Neutrophil functional studies in isolated cells

Measurement of interleukin-6, interleukin-1 beta and TNF-alpha in blood

hTtps://star-covid19.com/

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Press Release
Covid-19 brings research switch for Ashley

Published on 25 June 2020

When Ashley Giam left Singapore for the UK, she could not have imagined that the move would lead to her working on potential treatments for the deadliest pandemic the world has seen for a century.

The projects Ashley has worked on include STOP-COVID19, the clinical trial of brensocatib, an anti-inflammatory drug that is hoped may help to prevent the worst ravages of the novel coronavirus. Ashley is also now playing a leading role in the study of another new anti-inflammatory drug called SFX-01. This medication reduces lung damage through the pathway that Ashley has been studying during her PhD. She is now working in the laboratory to understand whether this medicine could reduce the number of coronavirus patients requiring mechanical ventilation and, ultimately, cutting death rates from the disease.

hTtps://www.dundee.ac.uk/stories/covid-19-brings-research-switch-ashley

As a double blind study, last week would have been a tad too early for any trial indications availableto Prof Chalmers, although every chance 100 have been recruited by now and so assessment by the DSMB could be underway, a process that Timbo intimated could take a couple of weeks, and presumably as the Lead investigator, Prof Chalmers would be privy to the interim data required by the DSMB and so Prof Chalmers might have a reasonable idea of any positive indications at this stage...more importantly Prof Chalmers decision to join Evgen's Scientific Advisory board at this stage could have been made on the the exploratory work being carried out in his lab, where exciting developments have been made in understanding "neutrophil dysfunction ", associated with ARDS/Covid and is part of the exploratory objectives of SFX-01 trial's, where blood and isolated cell samples are tested, and so judging by the excitement conveyed by Pro Chalmers and his team, this development could be highly significant to expectations on a successful conclusion to SFX-01 trial results. Gla holders...Exciting times...and fully expect the sp to continue its upward momentum...leaving behind all those that were selling up to and on the placing news...On and Up!!! :-)

Ps the green light from the DSMB will be a huge endorsement and no doubt will see a mad dash for shares...news of which could drop in the next week or so imho..;-)

Extremely encouraging that Prof Chalmers has joined Evgen's Scientific Advisory Board, and very interesting at this stage of proceedings that the following research by Prof Dinkova-Kostova, who also is a Scientic advisor to Evgen and one of the lead investigators on SFX-01's Covid/ARDS trial and has a lifes work focused on NRF2 and all things Sulforaphane, was also included in the newly released Evgen Investor Presentation...all bodes well imho. Gla :')

http://evgen.com/wp-content/uploads/2021/02/EVG-Investor-presentation-February-2021.pdf

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Can Activation of NRF2 Be a Strategy against COVID-19?

AntonioCuadrado

Albena T.Dinkova-Kostova

Acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 is largely the result of a dysregulated host response, followed by damage to alveolar cells and lung fibrosis. Exacerbated proinflammatory cytokines release (cytokine storm) and loss of T lymphocytes (leukopenia) characterize the most aggressive presentation. We propose that a multifaceted anti-inflammatory strategy based on pharmacological activation of nuclear factor erythroid 2 p45-related factor 2 (NRF2) can be deployed against the virus. The strategy provides robust cytoprotection by restoring redox and protein homeostasis, promoting resolution of inflammation, and facilitating repair. NRF2 activators such as sulforaphane and bardoxolone methyl are already in clinical trials. The safety and efficacy information of these modulators in humans, together with their well-documented cytoprotective and anti-inflammatory effects in preclinical models, highlight the potential of this armamentarium for deployment to the battlefield against COVID-19.

https://www.sciencedirect.com/science/article/pii/S0165614720301656