Member Info for Moneymunch

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He's been inside since day one, and so probably no window for the foreseeable with so much going on, anyways he was given a shed load of shares when he was appointed CEO and so lots of incentive to deliver shareholder value.....and plenty more news to look forward to in the coming weeks and months for Huw to realise that incentive. ...good news drop at anytime!!! Gl a:)

That's correct Ontarget, 6 trial sites originally and 10 trial sites according to the recruitment protocol, and Prof Chalmers also put an invitation out last week out for more potential trial sites to get in touch if interested. Tayside clinical unit also describes the recruitment now as Rapid , 58 patients recruited by 19th January from 9 that was confirmed 10th December, and so that equates to more than 50 a month, and so given the surging numbers of hospitalised patients, the recruitment of the first 100 patients to SFX-01 could be approaching fast....along with the Data and Safety Monitoring Board's assessment on the first 100 patients, Huw also confirmed that he will update the market on safety and if it's working and expects the trial to continue to Top line data, expected July...obviously the green light from the DSMB will be a huge endorsement and any positive detail from Huw could see a massive re-rate with any luck.....news of which could arrive much sooner than Finncap's April suggestion. Gl :-)

Tayside Clinical Trials Unit Retweeted
James D Chalmers
@ProfJDChalmers
·

Latest from the STAR-COVID trial announced today.

Rapid enrolment past 50 patients randomized.

Thanks @TASC_TCTU
@EvgenPharma
and funders @lifearc1

STAR-COVID is testing whether SFX-01 will improve outcomes in hospitalized patients with suspected COVID19
htTps://star-covid19.com

https://twitter.com/tasc_tctu?lang=en

No big sells as such, as Ontarget noted yesterday , and so maybe just flushing out short term traders and those betting short....before the next leg UP ...with any luck....Sooner or later.....;-)

Cheers compound, Evgen is all set for great things imho....multiple UPside potential on multiple targets, i really can't think of any other Bio with so much promise on so many fronts, from such a lowly sp and woefully and ridiculously undervalued market cap. .....Potential transformational news stacking UP, and sooner or later this will move BIG time imho, true and fair value and more , will prevail. Gl ;-)

Lol radar....you should try reading some then, to expand that pea sized brain of yours....ho ho ho ho ;-)

Consistent with this, SFX-01 significantly corrects the myeloproliferative disease found in Ptpn11D61G/+ NS mice. Thus, in conclusion, SFX-01 has potential as a new therapy for the treatment of NS.

Original language English
Awarding Institution

King's College London

Supervisors/Advisors

Philip Eaton (Supervisor)
Michael Shattock (Supervisor)

To assess if SFN-induced inhibition of SHP2 in the homozygous or heterozygous foetus could improve embryonic development, breeding pairs consisting of WT only or NS only parents were administered SFX-01 before conception and continued during pregnancy. SFX-01 treatment induced SFN-protein labelling of foetal tissue but also reduced litter sizes born from NS breeding pairs and genotyping showed only WT mice were born. This adverse effect may be due to SFN increasing the phospho-activation of ERK, which is deleterious in embryonic development of NS foeti.

However, SFX-01 had no adverse impact on the pregnancies of WT mice. Adult NS mice develop splenomegaly and myeloproliferative disease which can further develop into leukaemia. With this in mind, adult WT or NS mice were administered SFX-01 for 10 weeks to assess if prolonged treatment with the drug would inhibit SHP2 activity and reduce the incidence of myeloproliferative disease in the NS mouse model.

Using whole blood cell staining, ultrasound and flow cytometry, lower total white blood cell count, spleen size and myeloid cell count in the blood, bone marrow and spleen of NS mice by SFX-01 was seen compared to water only controls.

SHP2 activity was also attenuated in the spleen of both WT and NS mice, strongly suggesting this therapeutic action of SFX-01 was mediated by inhibition of SHP2 phosphatase activity.

Unexpectedly, even though phosphatase activity was inhibited following 4-day or 10-week treatment with SFX-01, this occurred without evidence of an SHP2-SFN adduct in the tissue of WT or NS mice.

Data from biochemical analyses involving biotinylated iodoacetamide (BIAM) labelling, the polyethylene glycol (PEG)-switch method or phenylarsinic acid (PAA)-binding, showed that SFN induced an inhibitory modification within SHP2 between two vicinal thiols within the active domain of the phosphatase, which to reiterate was not stable SFN adducts.

Data from complementary studies using site-directed mutagenesis of cysteines supported the concept that SFN adducts to SHP2 and inhibits it, which is followed by a proximal cysteine thiol mediating its removal or truncation, with the resulting modification maintaining inhibition of the phosphatase.

This SFN-induced inhibitory modification may be the formation of an intramolecular disulfide bond or perhaps the chemical modification of the SFN adduct to a dithiolethione.

Additional data has also shown that an SFN adduct can transfer from one thiol to another, so-called ‘trans-thiolation’. Using bovine serum albumin with an SFN adduct, which had been purified by large-format gel filtration on a protein chromatograph, transfer of the adduct to other cysteine-containing molecules such as haemoglobin or glutathione was observed.

SFX-01, a stabilised SFN variant in phase 2 clinical trials, inhibits WT SHP2 as well as a hyperactive Ptpn11D61G/+ mutant form expressed in many patients with NS.

Listening to Huw's latest interview, he talks about the potential of SHP2 over multiple cancer targets and "a very rare developmental disorder in children" and are now in the process of figuring out which disease to target to the one with the highest unmet medical need, which suggests that Noonan Syndrome would obviously under consideration given the following...Gla ;-)

https://youtu.be/xwflrBd83kg
......................

10/12/20

Blood cancer target

Professor Philip Eaton at Queen Mary University of London has shown that SFX-01 inhibits activity of the non-receptor phosphotyrosine phosphatase, SHP2 (coded by the ptpn11 gene). SHP2 is thought to be a significant factor in some cancers and we have recently agreed to support work in well-renowned university to investigate whether SFX-01 has potential in a specific blood cancer disease.

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

Prof Eaton was a supervisor on the following Doctoral Thesis. Gla ;-)

Sulforaphane-mediated inhibition of SHP2 as a potential pharmacotherapy for Noonan syndrome

Doctoral Thesis › Doctor of Philosophy

Joy Lynne Smith

Cardiovascular Sciences

Sulforaphane (SFN) is an electrophilic isothiocyanate which can adduct cysteine thiols within proteins. Protein targets of SFN were immunoprecipitated from cardiac tissue of wildtype (WT) mice following in vivo treatment with the electrophile using a validated polyclonal antibody developed in-house to pan-specifically detect SFN adducted to cysteines.

Combined with quantitative proteomics, this confirmed the non-receptor protein-tyrosine phosphatase, SHP2, as a target of SFN. SFN is intrinsically unstable at room temperature, therefore, a chemically stabilised variant developed by Evgen Pharmaceuticals (UK) known as Sulforadex (SFX-01), was used in subsequent experiments.

Using a commercially available phosphatase activity assay, SFX-01 was shown to inhibit recombinant SHP2 in vitro, as well as that in cardiac tissue of mice administered SFX-01 in their drinking water for 4 days. We speculated that SFX-01 may be therapeutic in diseases where SHP2 is hyperactive, such as Noonan syndrome (NS). Indeed, using an NS mouse model, Ptpn11D61G/+, a mutation resulting in hyperactivity of the phosphatase, SFX-01 time-dependently inhibited cardiac SHP2 activity. 100 % of homozygous and ~50 % of heterozygous Ptpn11D61G/+ mice die mid-gestation due to severe skeletal or cardiac defects, with the remaining ~50 % surviving to adulthood where they show non-cardiac features of NS.

Ps

Prostaphane® is a dietary supplement. It should not be used as a substitute for a healthy balanced diet and a healthy lifestyle.

Prostaphane® is not a medicine.

Composition

For one capsule: 10 mg of free, stabilized sulforaphane [CH3-SO-(CH2)4-NCS] from broccoli seeds.

Patented formula.

Ingredients: Maltodextrin, vegetal capsule (hydroxy propyl methylcellulose), broccoli seeds extract (Brassica Oleracea) titrated in sulforaphane, thickeners: acacia gum and magnesium stearate

Contact manufacturer

NUTRINOV

2 rue Julien Neveu

35531 NOYAL SUR VILAINE CEDEX

France

contact@nutrinov.com

15/6/20

INTELLECTUAL PROPERTY UPDATE

Our IP portfolio continues to be strengthened with a number of key patents being granted. The current status of the intellectual property portfolio is as follows:

-- From the "parent" patent family entitled "Stabilised Sulforaphane" patents are granted in Australia, Canada, EU, US, Japan and Hong Kong.

-- The principal manufacturing patent application, entitled "Methods of Synthesising Sulforaphane" is granted in Australia, China, Europe, Japan and further applications are pending in Brazil, Canada, US and India.

-- A second manufacturing patent which is directed to methods of isolating and purifying sulforaphane or analogues from natural sources has been granted in Europe, US, Japan and China.

-- The patent application providing protection around novel analogues based on sulforaphane, and entitled "Sulforaphane-Derived Compounds" is granted in Australia, China, Europe, Japan and the US and pending in Canada.

During the year composition of matter SFX-01 patents were granted both in Japan and Europe with a product claim for a complex of sulforaphane and alpha-cyclodextrin. The Group has long held broad compositional patent protection in the United States since patent grant in 2011 and in Canada since grant in 2014.

Furthermore, new composition of matter filings have been made which, if successful, would add a further 20 years of patent life to the key patent family.

Lol...how on earth can you have an IP lock on a natural botanical compound found in Broccoli etc....the whole point on the synthesis of SFX-01 and its analogues, is to provide a druggable clinical grade potent drug form of Sulforaphane that can be evaluated in medical clinical trials , and the strong IP protection in place, leaves SFX-01 and its analogues as the only druggable form of Sulforaphane that is of clinical patient trial grade .

Courtesy of Timbo from Adfvn. ...Gla :-)

Worth taking a look at the admission document (page 63 onwards) for the patent situation at the IPO and then the last update in the annual results (June 2020), see below, to get the full picture on the IP status.

Worth noting that they filed a brand new composition of matter patent application in April this year, the Chairman mentioned that they might do this at the last (physical) Investor update meeting in January this year. I think I recall the Chairman saying that the invention concerns a unique polymorphic form which is suprisingly more stable than the more obvious other polymorphic forms. If this application were to be granted, it would give protection out to 2040. The application was filed in April 2020, so it will publish in October 2021 (18 months after filing)

.......

SFX-01 is not "a natural-based product", it is manufactured through chemical synthesis. It is not nature identical either, as it comprises two different isomers (R and S) whereas natural occuring Sulforaphane consists entirely of just one isomer (R)

Sulforaphane

The isothiocyanate sulforaphane (SFN), originally isolated from broccoli, a cruciferous vegetable, as an inducer of the classical NRF2 target, NAD(P)H:quinone oxidoreductase 1 (NQO1) [76], is the most potent naturally occurring NRF2 activator, with well-documented antioxidant and anti-inflammatory effects [77].

The high bioavailability of SFN and its stabilized α-cyclodextrin-encapsulated version sulforadex (SFX-01) makes it an excellent candidate for alleviating excessive anti-inflammatory responses and protecting the lungs.

SFN has been found to be protective in animal models of respiratory disease, including an ARDS model in rabbits [78] and a hyperoxia-induced pulmonary injury model in mice [79].

It also limits RSV replication and virus-induced inflammation in the lungs of wild-type, but not NRF2-null, mice [80].

In HIV-1 transgenic rats, SFN increased GSH levels and the expression of NQO1, and restored the tight junctions between the alveolar epithelial cells [81].

In an in vitro model of influenza A infection, SFN reduced both viral cell entry and replication [82].

In addition, SFN suppresses HCV replication [83] and reduces HSV-1 virion production [29].

Interestingly, SFN inhibits nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)-, and pyrin domain-containing protein (NLRP) 1 and 3 inflammasomes (crucial innate immune components that shape host immune homeostasis) as well as pyroptosis, partly in an NRF2-independent manner [84].

Moreover, an interesting study conducted in smokers (a patient cohort with higher risk of lung infections, damage etc.) showed that SFN increased the expression of NQO1 in cells of nasal lavage fluid and, upon infection with live attenuated influenza virus, lowered the levels of IL-6 and viral load [85].

Sources of sulforaphane, including standardized broccoli extracts, dietary supplements, and encapsulated stabilized sulforaphane (Prostaphane and SFX-01) have been in numerous clinical trials for indications that range from lung disease to inflammatory diseases which are closely related to COVID-19 pathophysiology.

These include chronic obstructive pulmonary disease (COPD), asthma, allergy, rhinitis, aging, diabetes mellitus, Helicobacter pylori infection, and subarachnoid hemorrhage (Table 1). The clinical trials provide extensive pharmacokinetics, pharmacodynamics, safety, and efficacy information [77] that can be extrapolated to COVID-19.

Notably, most of these trials have recommended cruciferous-free diets during the study period to minimize baseline noise and accurately detect the plasma and urinary levels of sulforaphane and its metabolites [86].

htTps://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(20)30165-6

http://evgen.com/wp-content/uploads/2020/07/EVG-Investor-Presentation-06Jul20-FINAL.pdf

These novel analogues are also unstable and therefore require Evgen Pharma’s  Sulforadex®  technology so that they can be advanced into clinical studies.

The CEO confirmed in the following interview that SFX-01 is the only druggable , clinical grade form of Sulforaphan and is patented protected ...no one else has a clinical grade druggable technology. Gla holders :-)

16th December 2020

CEO interview.

"We're happy with our cash burn and we're happy with our funding well into the tail end of next year"

https://youtu.be/Pg2x00c9umM

TECHNOLOGY

Evgen Pharma’s core technology is Sulforadex®, a means of synthesising and concurrently stabilising the naturally occurring compound sulforaphane (or novel analogues based upon sulforaphane). Pure sulforaphane is an unstable oily liquid, which needs to be stored at -20 degrees C. A significant and growing amount of academic research has focused on sulforaphane but this work has been conducted either with frozen botanical extracts containing unstable sulforaphane or ambient temperature botanical extracts containing glucoraphanin, the chemical precursor of sulforaphane.

To date, the therapeutic effect of sulforaphane in academic research has focused on its ability to activate the transcription factor Nrf2 by covalently binding to Keap1. The activation of Nrf2 results in the production of a variety of proteins with antioxidative, anti-inflammatory and cytoprotective qualities.

Evgen Pharma’s Sulforadex® technology unlocks the medical and commercial potential of sulforaphane (and related novel analogues) by synthesising a stable, solid form, active pharmaceutical ingredient.  Lead product, SFX-01, is a patent-protected complex of sulforaphane and alpha-cyclodextrin in a stable powder. In addition to SFX-01, Evgen Pharma holds a world-wide exclusive licence to a series of novel sulforaphane analogues from the Spanish Research Council and the University of Seville. These novel analogues are also unstable and therefore require Evgen Pharma’s  Sulforadex®  technology so that they can be advanced into clinical studies.

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

Antonio Cuadrado

Albena T. Dinkova-Kostova

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.

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.

Dr Fahey also hails from John Hopkins University where the panacea qualities of sulforaphane were first discovered/established, the same background as one of SFX-01's lead investigators, who has spent a life's work on Sulforaphane and one of its key pathways NRF2 and obviously holds SFX-01's chances in high regard. Gla ;-)

Dundee researchers named among world’s most influential

Published on 18 November 2020

Six University of Dundee researchers have been named on a “who’s who” list of the world’s most influential academics.

hTtps://www.dundee.ac.uk/stories/dundee-researchers-named-among-worlds-most-influential?utm_content=buffer312af&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer

One of which is...... Prof Albena Dinkova-Kostova, Investigator of SFX-01's Covid-19 patient trials is also a listed Consultant to Evgen, and so no doubt has a vested interest in working towards a successful outcome and has a lifes work and research focussed on Nrf2 and the therapuetic potential and value of Sulforaphane. Gla ;-

Consultants

Professor Albena Dinkova-Kostova -“ Independent Scientific Advisor

Albena is a Professor of Chemical Biology at the Jacqui Wood Cancer Centre, Division of Cellular Medicine, University of Dundee School of Medicine. She obtained her PhD degree in Biochemistry and Biophysics from Washington State University and then joined the research group of Professor Paul Talalay, who discovered the anti-cancer effect of sulforaphane at Johns Hopkins University back in 1992. She has a core research interest in oxidative stress and inflammation and has published over 100 research papers including many on sulforaphane as an activator of the Nrf2 pathway and as a potential therapeutic strategy for protection against chronic degenerative diseases.

htTtps://evgen.com/about/management/

https://www.dundee.ac.uk/people/albena-dinkova-kostova

............................
Dr Rhonda Patrick, a big proponent of sulforaphane has organised a crowdcast featuring Dr Jed Fahey of John Hopkins on 7th Nov . Open to public.

https://www.crowdcast.io/e/special-qa-with-dr--jed/register

Profile https://www.hopkinsmedicine.org/pharmacology_molecular_sciences/faculty/bios/fahey.html
.....................................
Dr. Jed W Fahey
@jedosan
A very interesting paper from a very competent team at Texas Tech and elsewhere. Putting together #sulforaphane, #mitochondrial dysfunction, #oxidative damage and #Nrf2.

Aging Highlights
@aginghighlights
· Oct 17
Sulforaphane prevents age-associated cardiac and muscular dysfunction through Nrf2 signaling in mice.

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

ORIGINAL PAPER Open Access

Sulforaphane prevents age-associated cardiac and muscular dysfunction through Nrf2 signaling

First published: 17 October 2020

https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13261

ps bio******...where have you been hiding all this tim since registering on Lse yesterday?????

Lol...do you think Biobull**** is betting short by any chance......ha ha ha ha ha........SFX-01's saftey profile has been established in two phase 2 patient trial and is under evaluation by multiple high profile academia and was selected by LifeArc and University Dundee for Covid/Ards trial from over 130 drug candidates, and as ontarget states, unlike the vast majority of drugs already approved for multiple diseases, SFX-01's safety profile is confirmed favourable with mild to no side effects......Gla Holders......always a good sign when the detractors show their desperation......On and UP!!! ;-)