Evgen Pharma Share Discussion Threads

[moneymunch] 22/12/2020 10:53

Makes you think what will happen if positive data is reported from the Covid-19 patient trial.....has 100 patients been recruited yet???? News on the Solid Tumour collaboration could also be close, along with an update on progress towards the breast cancer trial and the rest of the pipeline......the pick up in buying volume, especially the 3 x 300k buys one after the other bodes very well imho....Gl ;-)

[bumpa33] 22/12/2020 10:17

Makes you think too - our numerous shots on goal are at minuscule cost compared to the development and trial costs of many/most of the big players. Which reminds me of another interesting comment the CEO made in that interview re: coming up against the big boys...

[bumpa33] 22/12/2020 10:03

Hmm, not quite $1.35b down the drain, but not a great start... 😳

[moneymunch] 21/12/2020 19:23

I reckon Novartis would have been better off waiting for SFX-01's interim results for ARDS/ Covid-19...Gla ;-)

[moneymunch] 21/12/2020 19:19

Ouch!!!!

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The $1.35 billion deal recently signed by Novartis for a ARDS/Covid treatment still in clinical trial, has now received FDA fast track designation after the release of early interim results.....and so a striking example of SFX-01's potential value and prospects for ARDS/Covid, if positive data is observed. Gla ;-)


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Novartis Inks $1.35 Billion Deal with Mesoblast for Remestemcel-L for COVID-19 ARDS

Published: Nov 20, 2020

Novartis inked an exclusive worldwide license and collaboration deal with Australia-based Mesoblast to develop, commercialize and manufacture remestemcel-L for acute respiratory distress syndrome (ARDS), including when it is linked to COVID-19. The company plans to launch a Phase III trial in non-COVID-19-related ARDS shortly after closing the deal. The drug is currently being evaluated in a Phase III trial in COVID-19-related ARDS.



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21/12/20

Mesoblast’s stem cell therapy fails to meet primary endpoint in COVID-19 study
Remestemcel-L was being studied in patients with COVID-19-related acute respiratory distress

Australian biotech company Mesoblast announced on Friday that its stem cell therapy remestemcel-L failed to meet the primary endpoint in a phase 3 COVID-19 trial.

Remestemcel-L was being studied in ventilator-dependent COVID-19 patients with moderate-to-severe acute respiratory distress (ARDS).

According to Mesoblast, the trial was aiming to achieve a primary endpoint of 43% reduction in mortality at 30 days for treatment with remestemcel-L, in addition to maximal care.

However, following a third interim analysis of the first 180 patients, the trial’s Data Safety Monitoring Board (DSMB) reported that it is not likely the treatment will achieve that specified endpoint.

The trial has not yet yielded data on the secondary endpoints, which includes days alive off mechanical ventilation, overall survival, days in intensive care, duration of hospitalisation and cardiac, neurological and pulmonary organ damage.

Although Mesoblast maintained there were no safety concerns, the DSMB recommended that the trial should be completed with the currently enrolled 223 patients, rather than continue to enrol up to 300 participants, as originally planned.

The trial researchers will continue to evaluate all enrolled patients for 60 days of follow-up to study the potential treatment effects on these outcomes.

In a statement, Mesoblast said that it and Novartis “will both analyse these results to identify meaningful clinical outcomes that may guide decisions on the development programme for remestemcel-L in non-COVID ARDS”.

[amaretto1] 21/12/2020 17:48

Decent day :-)

[moneymunch] 21/12/2020 15:41

Sounds good Bumpa, and just the start of the UPside journey to fair value and beyond, and looks like someone close to the action has just picked up 900k shares on the cheap. Gl ;-)

[bumpa33] 21/12/2020 15:35

nice to see interest growing, but we’re a long way off fair value.

Forgot to mention last week that it’s great to see another mm getting actively involved, up until now it’s been too easy for a certain entity to control the play.

[moneymunch] 21/12/2020 15:22

Make that 3 x 300k buys just in...Tick Tock!!! :-)

[moneymunch] 21/12/2020 15:19

2 x 300k buys just in...Gla :-)

[moneymunch] 21/12/2020 13:05

Another recent deal on SHP2 that Evgen has under evaluation with 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.....endless UPside potential it seems...Gla ;-)


AbbVie pens cancer pact with U.S.-China biotech Jacobio

Jun 1, 2020

AbbVie has signed a new pact to focus on SHP2 inhibitors, which target a key node in cancer and immune cells, from early-stage biotech Jacobio Pharmaceuticals.

Under the deal, financials of which are not being shared, AbbVie nabs an exclusive license to the China and U.S. company’s SHP2 portfolio.

Jacobio will work on early global clinical trials of the two leading candidates out of this portfolio, namely JAB-3068 and JAB-3312, but now AbbVie will start covering R&D expenses.

[2seabass] 21/12/2020 12:48

Just added more given steady rise. Hopefully before the herd arrives shortly !!.

[moneymunch] 21/12/2020 12:43

Looking good and strong and still cheap as chips given the Transformational upside potential opportunity ahead. Gla :-)

[moneymunch] 21/12/2020 11:59

This was posted on Lse yesterday, if oncology and Ards had been mentioned, I'd be very excited, but you never know!!!??? ;-)

Ps sooner or later a Major player will Express an interest on the flow of positive data from Evgen's multiple disease pipeline. Gla :-)

Nolupus - Lse

Gsk and a UK biotech ...

Wondering if this is a possibility for EVG ?

[mesquida] 21/12/2020 11:49

Kingalf, can we pop the champagne corks now, or do you still think that it might be a bit premature. It is certainly a good performance today in a soggy market, but the volume is nothing special.

[mesquida] 21/12/2020 11:49

Kingalf, can we pop the champagne corks now, or do you still think that it might be a bit premature. It is certainly a good performance today in a soggy market, but the volume is nothing special.

[moneymunch] 21/12/2020 07:32

"reflecting evidence targeting SHP2 counters adaptive resistance to the red-hot approach to treating cancer."



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.

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Genentech pays Relay $75M for cancer drug, plans KRAS combo

Dec 14, 2020

Genentech has struck a deal to license Relay Therapeutics' SHP2 inhibitor for $75 million upfront. The Roche subsidiary plans to combine the drug with its KRAS G12C inhibitor, reflecting evidence targeting SHP2 counters adaptive resistance to the red-hot approach to treating cancer.

Excitement about finally being able to design drugs that bind to frequently mutated oncogene KRAS has been tempered by early clinical data showing the limitations of the use of KRAS G12C inhibitors as single agents. The reactivation of the inhibited pathway, known as adaptive resistance, is one source of concern for KRAS drugs and other targeted therapies. Researchers at New York University School of Medicine found SHP2 inhibition may help by boosting G12C-I accessibility to mutant KRAS.

Relay has done its own assessments on the combination, reporting in its IPO paperwork earlier this year that it has shown the benefits of pairing a SHP2 inhibitor with a KRAS G12C agent in preclinical studies. The SHP2 inhibitor, RLY-1971, began phase 1 development in solid tumor patients earlier this year.

[moneymunch] 20/12/2020 10:30

The ACE2 receptor appears central to the spread of Covid-19, and the research by one of SFX-01's lead investigators highlights the therapeutic potential of Nrf2 activators and influence over ACE2, and no doubt one of the compelling reasons why SFX-01 was selected for Covid-19 patient trials.....Gla Holders....Positive data will be transformational for all concerned. :-)

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What do we know about this new SARS-CoV-2 variant?

It’s been snappily named VUI-202012/01 (the first “Variant Under Investigation” in December 2020) and is defined by a set of 17 changes or mutations. One of the most significant is an N501Y mutation in the spike protein that the virus uses to bind to the human ACE2 receptor. Changes in this part of spike protein may, in theory, result in the virus becoming more infectious and spreading more easily between people.



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In the search for treatments for COVID-19, many researchers are focusing their attention on a specific protein that allows the virus to infect human cells. Called the angiotensin-converting enzyme 2, or ACE2 “receptor,” the protein provides the entry point for the coronavirus to hook into and infect a wide range of human cells. Might this be central in how to treat this disease?



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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.

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SARS-CoV-2 Biology and Potential Crosstalk with NRF2

The SARS-CoV-2 genome encodes non-structural proteins (nsp) that are required for replication, structural proteins including spike (S), envelope (E), membrane (M), and nucleocapsid (N), and accessory proteins ORF3, 6, 7a, 7b, 8, and 9b that interact with the host cells [38].

The receptor-binding domain (RBD) located in the S protein of SARS-CoV-2 interacts with the angiotensin-converting enzyme 2 (ACE2) of host cells to allow viral entry (Figure 1) [39].

The use of ACE inhibitors/angiotensin-receptor blockers, which are widely prescribed to patients with cardiovascular pathologies [40], is currently being considered for COVID-19 (clinical trial numbersi NCT04311177 and NCT04312009 for the use of losartan) because angiotensin II, the target of ACE inhibitors, has vasoconstrictive, proinflammatory, pro-oxidative, and prothrombotic effects [41].

However, these inhibitors alter the balance ACE/ACE2 and increase ACE2 levels, thus potentially increasing the number of docking sites for viral entry [42].

NRF2 deficiency is known to upregulate ACE2, whereas its activator oltipraz reduces ACE2 levels [43], suggesting that NRF2 activation might reduce the availability of ACE2 for SARS-CoV-2 entry into the cell (Figure 1).

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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].

[moneymunch] 20/12/2020 09:12

Presumably yes, which will be disclosed on patent filing and scientific paper publication , which potentially suggests a commercial collaboration rather than academic , would they need to keep it quiet if it was another University, maybe and certainly another exciting update to look forward to. Gl ;-)

[gimmetheloot] 19/12/2020 22:53

Is there a reason why he can’t say more?

[moneymunch] 19/12/2020 21:14

Ps the CEO stated that he would make disclosure of the collaboration on patent filing and scientific paper preparation, and so probably not associated with UoM,unless we get a RNS this coming week...something similar nevertheless, " the best preclinical data seen on very hard to treat condition "...Bring it on!!! :-)

[moneymunch] 19/12/2020 21:00

Could be, given the simalarites in the research article I posted about University of Michigan's Miracle treatment...though since then I have come across their patent filing , which revolves around the nanoparticle drug delivery method of passing the blood brain barrier which does mention sulforaphane amongst many other drugs, and I've also come across their white paper Scientific publication, that makes no reference to SFX-01 or Evgen, but is comprehensively in detail about the STAT3 pathways potential. Gl :-)

[gimmetheloot] 19/12/2020 19:42

What other tumours is Huw referring to in the proactive interview? Is it Glioblastoma?

[lovewinshatelosses] 19/12/2020 19:19

Historically, viruses tend to mutate into more benign strains, while also becoming more infectious. Clever and logical process to undertake.
Hopefully this will indeed refresh interest in this space. Still extremely undervalued, compared to similar outfits, some of of which are less advanced and have fewer strings to their bow than EVGEN. We shall see.