Member Info for Moneymunch

The gulf in valuation between Reata - Market Cap $5.35 Billion, and Evgen - Market Cap £12.7m is truly staggering. Reata's lead drugs are more clinically advanced but SFX-01 isn't that far behind in the current phase 2/3 Covid-19 patient trials and the phase 2/3 trial for Breast Cancer that are being prepared, and so plenty of reasons why a Major Pharma would be very interested in a strategic partnership to advance SFX-01's undoubted huge commercial potential which also inludes the lucrative non-pharma healthcare supplement industry.

Maybe Reata could be an interested party if they wanted to monopolise the NRF2 activator space, whereby they would advance SFX-01 as a stand alone therapy or potentially in combination with their lead drugs, although any Major player will do, and the chances of a commercial JV and/or stratgeic partnership for Evgen look incredibly strong imho. Gla ;-)

Reata....

Reata is a clinical-stage biopharmaceutical company that develops novel therapeutics for patients with serious or life-threatening diseases by targeting molecular pathways involved in the regulation of cellular metabolism and inflammation. Reata’s two most advanced clinical candidates (bardoxolone methyl and omaveloxolone) target the important transcription factor Nrf2 to restore mitochondrial function, reduce oxidative stress, and resolve inflammation.

Omav=omaveloxolone; Bard=bardoxolone methyl; ADPKD=autosomal dominant polycystic kidney disease; lgA=immunoglobulin A; CKD=chronic kidney disease

Bardoxolone methyl, omaveloxolone, RTA 901 and RTA 1701 are investigational drugs.

Safety and efficacy have not been established by any agency.

Overview

In Alport syndrome (AS), bardoxolone methyl targets molecular pathways that promote the resolution of inflammation, which if unchecked, leads to chronic inflammation, and ultimately, progressive loss of kidney function. Bardoxolone methyl is being studied in Reata’s pivotal, registration, phase 2/3 CARDINAL trial

In Friedreich’s ataxia (FA), omaveloxolone targets the chronic inflammation and mitochondrial dysfunction associated with this neurologic disorder. Omaveloxolone is being studied in the pivotal, registration, MOXIe trial

Reata’s lead drug candidates, bardoxolone methyl and omaveloxolone, have novel mechanisms of action that target the underlying pathogenic pathways involved in chronic inflammation. Research has shown that prolonged mitochondrial dysfunction and oxidative stress, including their molecular components, proinflammatory mediators called cytokines and ROS, are major contributors to chronic inflammation.

https://www.reatapharma.com/our-science/pipeline/

A weight of scientific evidence on SFX-01's potential and why LifeArc no doubt, selected SFX-01 for Covid-19 patient trials from over 120 other potential drug candidates. Excitement building. Gl ;-)

14/7/20

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 stabilised a-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 the GSH levels and the expression of NQO1, and restored the tight junctions between the alveolar epithelial cells [81] and in an in vitro model of influenza A infection, SFN reduced both viral cell entry and replication [82]. Additionally, SFN suppresses HCV replication [83] and reduces HSV-1 virion production [29]. Interestingly, SFN inhibits nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeats (LRR)- and pyrin domain-containing protein (NLRP) 1 and 3 inflammasomes (critical innate immune components that shape the host immune homeostasis), and pyroptosis, partly in an NRF2-independent manner [84]. Moreover, an interesting study conducted in smokers (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].

Standardized broccoli extracts and dietary supplements as sources of sulforaphane, as well as encapsulated stabilized sulforaphane (Prostaphane and SFX-01) have been in numerous clinical trials for indications that range from lung diseases to inflammatory diseases which are closely related to COVID-19 pathophysiology. These include chronic obstructive pulmonary disease (COPD), asthma, allergy, rhinitis, ageing, diabetes mellitus, Helicobacter pylori infection, and subarachnoid haemorrhage (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 in order to minimize baseline noise and be able to detect accurately the plasma and urinary levels of sulforaphane and its metabolites [86].

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359808/

Courtesy of Bumpa from Advfn.

A must read this...

“Can activation of NRF2 be a strategy against COVID-19?”

httPs://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359808/

“Nonetheless, the wealth of safety and efficacy information for NRF2 activators such as sulforaphane and bardoxolone methyl, that are already in advanced clinical trials for other indications, provides a clear route for their testing in randomized clinical trials in patients with COVID-19. If successful, this therapeutic strategy could be mobilized rapidly in order to improve recovery and decrease the need for mechanical ventilation in patients with severe COVID-19, relieving the enormous strain that is currently being experienced by intensive care units worldwide”

Anytime noix, and a bit more detail in the following link. Gl ;-)

https://www.nature.com/articles/s41388-020-1335-z

Noix, SFX-01 was confirmed to improve clinical outcome of patients on Tamaxifon and fulvestrant , Astra Zeneca's two blockbuster cancer drugs. Gl ;-)

Targeting STAT3 signalling using stabilised sulforaphane (SFX-01) inhibits endocrine resistant stem-like cells in ER-positive breast cancer

ABSTRACT

PURPOSE Estrogen receptor (ER) positive breast cancer is frequently sensitive to endocrine therapy. Multiple mechanisms of endocrine therapy resistance have been identified, including cancer stem-like cell (CSC) activity. Sulforaphane (SFN) has previously been shown to target CSCs but its mechanism of action is unclear. Here we investigate SFX-01, a stabilised formulation of SFN, for its effects on breast CSC activity in ER+ preclinical models and to study its mechanism.

EXPERIMENTAL DESIGN CSC activity was measured by mammosphere formation efficiency (MFE), aldehyde dehydrogenase (ALDH) activity, and tumor formation using patient samples and patient-derived xenograft (PDX) tumors treated with SFX-01 alone or in combination with tamoxifen or fulvestrant. Gene expression and SFN target proteins in treated samples were assessed.

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

Exciting prospects with the very real chance of a commercial JV at anytime, and quite amazing how far this is under the radar at the moment given the undoubted potential.

If SFX-01 was confirmed a therapuetic benefit for the treatment of lung conditions in Covid-19 , then this would literally go into orbit...£1 a share, £2 a share...even £5 a share would only equate to a market cap of £680m....which would still look cheap on the World stage for a confirmed treatment for Covid-19 at all stages of the condition...Fill Ya Boots... imho!!! ;-)

ps radar, just to let you know, off for another 18 holes soon with a few mates on a beautiful Surrey track and so will be otherwise engaged , just incase i miss out on any action....Scorchio!!! ;-)

pps Next week for news!!!??? Highly likely...;-))))

Major shareholder Number of shares Percentage holding

SPARK Impact 16,186,446 11.9%

Richard Griffiths & controlled undertakings 14,408,000 10.6%

AXA Framlington 11,848,884 8.7%

Seneca Investment Mgrs 7,243,097 5.3%

Mercia Fund Mgrs 5,913,818 4.3%

Newlands Capital 5,889,815 4.3%

TS Capital 5,078,334 3.7%

There are 136,382,241 ordinary shares in issue, of which 17% is not in public hands

This page was last updated on 13 July 2020

Investor Presentation June 2020

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

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

AGM Presentation 16th July 2020

http://evgen.com/wp-content/uploads/2020/07/2020-AGM-presentation-16July20.pdf

How good would it be if that was down to SFX-01...Gla ;-)

Zero confirmed coronavirus deaths in Scotland for a week

There are five new cases in Scotland overall, taking the country’s total over the course of the pandemic to 18,373.

A total of 611 people are in hospital overall with Covid or Covid symptoms, down five on the day before.

Of those, just six people are being treated in intensive care, a decline of six – and only two are confirmed to have coronavirus.

https://news.stv.tv/scotland/zero-confirmed-coronavirus-deaths-in-scotland-for-a-week?top

Another late reported buy from yesterday aternoon....5.6m at 9p....Gla ;-)

On and UP and back to double figures, amazing how so many were happy to give up their shares cheaply over the past couple of weeks...Gla Holders....Potential transformational news stacking UP!!! ;-)

A late 5.7m buy at 9p also reported after hours.....a BIG ble day ahead with any luck. Gla holders ;-)

On the golf course at the so missed all the action....a VERY BIG DAY TOMORROW IMHO Gla:-)

Lol radar, your post 8/7/20 suggests that you're the complete and utter clueless numptie, Evgen are not in the Covid-19 vaccine space and it's laughable if you think there'll be multiple cures for Covid-19 anytime soon....Do some research you moron. ;-)

radar

RE: Covid-19 Patient Trial08 Jul 2020 16:46

They would have been much better off sticking to what they know best that’s cancer treatment.

The covid vaccine space is packed out and at the way it’s going there will be multiple cures for covid.

They should stick to what they know best.

Not a good strategy to jump on every bandwagon passing.

Lol, just need some news...something BIG is going on behind the scenes imho......fingers crossed for a stellar Rns or two or three...;-)

Cheap as chips....Tick Tock...:-)

Lol radar, Evgen are not developing a vaccine you clueless numptie ha ha ha ha ;-)

 0 0

Remdesivir when compared with placebo was associated with clinical improvements in some of the outcomes and fewer serious adverse events.

The findings in the review suggest that factors to consider when using remdesivir as a treatment option for COVID-19 in patients with mild or moderate, or severe disease include the timing of initiation of treatment at the onset of symptoms, disease severity (this includes the need for oxygen support, non-invasive ventilation, invasive ventilation or organ support, most of the patients in the studies had severe COVID-19) and the underlying clinical status of the patient and age. These may have important effects on the outcomes of treatment. Remdesivir should only be administered by intravenous infusion which may limit its use.

.....

In the large-scale ACTT-1 study conducted by the National Institutes of Health, intravenous remdesivir already showed it could cut recovery time by four days, or about 31%, among hospitalized patients. But its benefits appear less significant for patients with mild or moderate disease.

Early positive indications from SFX-01's Covid-19 patient trials, will very likely be made public Imho... gla :')

....

Although the study is still ongoing, an independent data and safety monitoring board overseeing the trial reviewed the data and shared their preliminary analysis with NIAID. Due to the public health implications, NIAID made these primary results public, and they were published on May 22, 2020, in the New England Journal of Medicine.

https://www.nih.gov/news-events/nih-research-matters/early-results-show-benefit-remdesivir-covid-19

Early positive indications of the orally administered SFX-01 could be made public or at least information shared with other world health authorities, especially now that the US has bought the entire world supply of the only drug that has shown to be effective in current ongoing Covid-19 patient trials , so far!!! Gl ;-)

"Remdesivir, the only drug cleared to treat COVID-19, is given by intravenous infusion, making it a great choice for hospitalized patients, but less convenient for outpatients."

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

Coronavirus: US buys up almost entire world supply of COVID-19 drug remdesivir
American officials have bought up all of the remdesivir available for July and 90% of stocks for August and September.

Wednesday 1 July 2020

The US has bought up almost the entire global supply of one of two drugs used to treat coronavirus which UK patients helped test.

Remdesivir, which was developed to treat Ebola, is produced almost exclusively by US pharmaceutical giant Gilead Sciences - and it has been priced at $2,340 (£1,892) per patient in wealthier nations.

The company has agreed to send nearly all of its supply of the drug to the US over the next three months.

Nadhim Zahawi believes that competition for coronavirus drugs undermines spirit of making treatment available for everyone.

This means remdesivir will not be available for use on patients in the UK and Europe until October, Dr Andrew Hill, a senior visiting research fellow at Liverpool University, told Sky News.

He said: "This deal that's been struck by America means that people with COVID-19 in the UK can't get access to these treatments that would get them out of hospital quickly and might improve their chances of survival.
Advertisement

"So far, we know that for the next three months there will be no supplies of remdesivir - America will take the drugs and we won't have access to them. That's the case in the UK and Europe."

UK patients took part in the clinical trials that showed that the drug worked, Dr Hill said. "A lot of drugs haven't worked, so I think the people in Britain deserve something in return from the United States," he said.