Evgen Pharma Share Discussion Threads

[bumpa33] 03/4/2021 19:17

Here, try this for a start on ARDS





Note the causes below, rather more than ‘just’ pathogens...


Causes[edit]
There are direct and indirect causes of ARDS depending whether the lungs are initially affected. Direct causes include pneumonia (including bacterial and viral), aspiration, inhalational lung injury, lung contusion, chest trauma, and near-drowning. Indirect causes include sepsis, shock, pancreatitis, trauma (e.g. fat embolism), cardiopulmonary bypass, TRALI, burns, increased intracranial pressure.[10] Fewer cases of ARDS are linked to large volumes of fluid used during post-trauma resuscitation.[11]

[bumpa33] 03/4/2021 18:59

If you can’t grasp the simple stuff, maybe stick to engine oil companies.

[bumpa33] 03/4/2021 18:58

You’re not preventing ARDS, you are treating and alleviating the symptoms of it ffs.

And btw, It is not Neuroblastoma (which originates in the adrenal glands and usually affects young children), it is glioblastoma and glioma (which are brain cancers)

[diamondstar1] 03/4/2021 18:52

Moneymunch - thanks for this valuable information. So, it’s a sink or float situation with the upcoming interim analysis.

Yet, the patient population is potentially very heterogeneous - you may get some with background viral infections (eg COVID-19, influenza, etc) and bacterial pneumonias (staph, strep etc). Problem is Regulatory pathway is not clear to me- how do you get a drug approved for prevention of ARDS with various underlying pathogenic causes? I’m really not sure what FDA and EMEA will ask for - in terms of a pivotal Ph3 design.

[bumpa33] 03/4/2021 18:39

The “STAR trial is a risky one”

Priceless 🤦🏼‍♂️🤦🏼‍♂️🤦🏼‍♂️🤦🏼‍♂️

[moneymunch] 03/4/2021 16:23

Evgen confirmed 17/2/21 that the Data Safety Monitoring Board would assess safety on the first 60 patients and results would be published early Q2, yet results arrived earlier than stated on 11/3/21 confirming no safety concerns and Evgen confirmed at 11/3/21 that the DSMB would then assess the first 100 patients and Prof Chalmers would assess for efficacy, with results expected during Q2, and so it's highly possible that this assessment could already be in progress and results could arrive sooner rather than later....Gla holders...Excitement building in anticipation, this could very likely multi-bag on positive data. ;-)

[moneymunch] 03/4/2021 16:14

11/3/21


Following this positive step, the next event in the trial involves an assessment of safety and futility by the DMC of unblinded data on the first 100 patients treated. In addition to the DMC safety and futility assessment, Dundee University has decided to review the top-level unblinded data in a preliminary assessment of possible efficacy. This may lead to adjustments to the design of the trial for remaining patients, including in-patient numbers, and possibly early termination for either safety, futility or alternatively, strong efficacy. It is expected that this initial data will be available during Q2 of the calendar year 2021.

[diamondstar1] 03/4/2021 16:11

Moneymunch - are you sure there is going to be a preliminary efficacy assessment - performed by Prof Chalmers? All I could find was some info suggesting that the DSMB would meet to discuss safety results based on 60 patients. Efficacy analysis after 60 patients - may not be very helpful in my opinion. Information from Evgen suggest that full efficacy results will be available late this year or early next year. Thanks.

[moneymunch] 03/4/2021 15:05

Lol...better wait for Prof Chalmers preliminary efficacy assessment then...a defining moment if there ever was one....Gl :-)

[diamondstar1] 03/4/2021 14:35

My simple analogy is like this. I agree that Evgen have clearly a pharmacologically active therapy - SFX-01. Let’s just say that Evgen were a oil company that developed engine oil products, that helped car engines last 30% longer. In the first study that Evgen conducted, they decided to run a study in cars, by replacing engine oil for cars that reached the garage (ie reached hospital) that had broken down. That was the SAH study. The study didn’t show benefit. Then they start another study in garages, looking for another type of broken down vehicle - that’s the ARDS study. Why not go down the proven route that other companies developing NRF-2 activators have taken and succeeded - ie target patients with chronic inflammatory conditions (in the general community) that don’t have a life-threatening condition?

[diamondstar1] 03/4/2021 14:14

Likewise, SFX-01 was shown to be effective in acute SAH in various animal species... not an uncommon finding, to see efficacy in animals but not humans.

Look at the 1000s of drugs tested in acute stroke in humans that failed at Ph2/3 - these drugs all had fantastic animal data to support development in humans! Even Big Pharma has lost billions here. The key here is that treating acute conditions with an interventional drug therapy - is a very risky trial, as historical information (eg from acute stroke trials) would show.

[on target] 03/4/2021 14:09

It has been shown to be effective against acute ARDS in rabbits, so the mechanism is there.

[diamondstar1] 03/4/2021 13:35

However, one big risk I’d like to highlight to all of you - is that this STAR trial is now building up to be very similar to the trial in Subarachnoid Haemorrhage (SAH) - that was unsuccessful a couple of years ago.
There is clear evidence that NRF-2 activators have anti-inflammatory effects, however these effects have been shown to be beneficial in a chronic and preventative setting (eg management of patients with multiple sclerosis, psoriasis, etc).
There has not been a trial with NRF-2 activator in an acute setting in patients, which has been successful. Example, you take a sick patient in hospital with SAH (or potential ARDS) start them on NRF-2 activators and expect a benefit. The pathological process involved in these patients may be different, and more difficult to reverse.
Therefore, it is my personal opinion that STAR trial is a risky one, but only time will tell...

[diamondstar1] 03/4/2021 13:19

OK - thanks for the info that ARDS of any cause is being targeted by the STAR trial. That is helpful information.

[on target] 03/4/2021 13:07

Regarding strategy and medical/scientific expertise, isn't this why they've recruited the new CBO and are in the process of recruiting a CSO?

Strategy is to prove up the data then sell/out-licence to big pharma, who have the funding to take it all the way as you said.

[on target] 03/4/2021 12:57

- Acute respiratory distress syndrome (ARDS) is defined as an acute process, which results in moderate to severe loss of lung function.

- Approximately 150,000-200,000 Americans will be diagnosed with ARDS each year. Worldwide, that number is approximately 2.2 million

- There is no known prevention for ARDS at the present time. Nor is there any known cure. ARDS patients are treated with supportive care, most often in the Intensive Care Unit.

- Although ARDS is always a critical syndrome, more than half of the patients who are diagnosed with ARDS survive.

[diamondstar1] 03/4/2021 12:17

I’m still pessimistic on Evgen at the moment- till I see them sort out their development strategy and medical/scientific expertise.

For example, in COVID-19 treatment - can anyone explain how SFX-01 will fit into the overall treatment regime or treatment guidelines for COVID-19? You’ve got large numbers of the population being treated with vaccines at the moment - what happens when herd immunity is achieved? You will have very little patients hospitalised with COVID-19 with ARDS. Moreover, emergency usage of monoclonal antibodies has been approved for use for treating people in the pre-hospital phase - to reduce the number of severe cases of COVID-19. Hence, in my mind, Evgen may even face a unique challenge of completing the STAR trial, as the number of COVID hospitalisations decrease, and the number of potential ARDS cases decreases. Even if the interims for STAR-trial are positive, and they do somehow complete enrolling 300 patients (example, in 1 years time when COVID pandemic is largely over), they still may likely need to complete a larger Ph3 trial, I am assuming? Then there is a question how SFX-01 will be able to compete with 1126 other drugs being developed for COVID-19 at present. Essentially, it is the big Pharma who have the huge pockets and abundant expertise who are succeeding in this game e.g. Pfizer, AstraZeneca, J&J. Because adequate funding means that they can accelerate development plans, and get drugs approved in a timely manner.
With regards to the cancer space. Evgen have not succeeded in the breast cancer space for the past 5 years. What evidence do we have that they possess the knowledge and experience to succeed in glioma, which has new therapies such as monoclonal antibodies and conventional radiotherapy?

[moneymunch] 02/4/2021 15:53

As well as SFX-01's focus on Nrf2 for Covid/Ards, its influence over STAT3 could also be of significance in proving efficacy. Gla ;-)




Contribution of STAT3 to the pathogenesis of COVID-19

Highlights

STAT-3 can be activated by numerous cytokines during COVID-19.

STAT-3 is hyper-activated and can play a central role in COVID-19 pathogenesis.

Activated STAT-3 can promote hyper-inflammation, lung fibrosis and thrombosis.

Activated STAT-3 promotes lymphopenia and impairs anti-virus immune responses.

STAT3 may be a potential therapeutic target for the treatment of COVID-19.

[moneymunch] 02/4/2021 10:37

We're also awaiting news on Evgen's new cancer target related to SFX-01's influence over the SHP2 pathway.....a RED HOT Oncology target for lucrative licensing deals....here's a few recent examples. Gla ;-)


TOKYO, Japan; 13 January, 2021

Taiho Pharmaceutical Co, Ltd., (hereinafter Taiho) announces that it and Astex Pharmaceuticals (UK), (hereinafter Astex), both Otsuka group companies, have granted an exclusive license under their joint, small-molecule drug discovery program targeting SHP2 to Merck & Co., Inc., Kenilworth, NJ, USA, known as MSD outside the United States and Canada (hereinafter MSD) through a subsidiary.



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Erasca Unveils Its First Strategy to Erase Cancer, Accelerated by Expansion of Precision Oncology Pipeline and Dosing of First Patient

Successful additions of ERAS-601 and ERAS-007, potential best-in-class inhibitors of SHP2 and ERK, respectively, enable “MAPK Clamp” approach to shut down RAS/MAPK pathway

Erasca doses first patient in FLAGSHP-1 study, Erasca’s first clinical trial
January 06, 2021 08:00 AM Eastern Standard Time

SAN DIEGO--(BUSINESS WIRE)--Erasca, a company whose mission is to erase cancer, announced the expansion of its pipeline of precision oncology therapies via two exclusive, worldwide agreements directed at targeting critical upstream and downstream nodes in the RAS/MAPK signaling cascade, one of the most frequently mutated oncogenic pathways in cancer. ERAS-601, a potential best-in-class inhibitor of the Src homology region 2 domain-containing phosphatase-2 (SHP2), was licensed from NiKang Therapeutics, Inc. ERAS-007, a potential best-in-class inhibitor of the extracellular signal-regulated kinase (ERK), the most distal node of the RAS/MAPK pathway, was acquired from ASN Product Development, Inc., a wholly owned subsidiary of Asana BioSciences, LLC.



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October 26, 2020

News briefing: AstraZeneca follows Amgen down KRAS/SHP2 combo path;

Revolution Medicines is adding AstraZeneca to its roster of clinical collaborators, lending its lead drug, RMC-4630, for a study pairing it with the pharma giant’s KRAS G12C program.

AstraZeneca will sponsor and conduct the study once its now preclinical drug is ready for human studies, an arrangement similar to the deal Revolution has with Amgen on sotorasib.

Drug combinations are likely to be critical for defeating inherent drug resistance mechanisms exploited by RAS-addicted cancers, CEO Mark Goldsmith said in a statement.


An allosteric SHP2 inhibitor, RMC-4630 attracted Sanofi for a partnership that involved $50 million upfront, 80% of the R&D cost, and a swath of milestones adding up to $520 million. Revolution is also working on a pipeline from its buyout of Warp Drive Bio of drugs that directly inhibit oncogenic RAS(ON) variants, including KRASG12C(ON) and KRASG12D(ON).



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December 21, 2020

Financing

China

Months af­ter strik­ing SHP2 deal with Ab­b­Vie, Ja­co­bio pulls in $174M+ from Hong Kong IPO


The sea­soned crew at Ja­co­bio has raised $174.1 mil­lion on its HKEX de­but, fu­elling a pipeline an­chored by two Ab­b­Vie-part­nered al­losteric SHP2 in­hibitors.

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AbbVie and Jacobio Announce Strategic Collaboration to Advance SHP2 Inhibitors

News provided by
AbbVie

Jun 01, 2020, 01:00 ET

Share this article

NORTH CHICAGO, Ill. and BEIJING, June 1, 2020 /PRNewswire/ -- AbbVie (NYSE:ABBV), a research-based global biopharmaceutical company, and Jacobio Pharmaceuticals, a clinical-stage pharmaceutical company, today announced a global, strategic collaboration to develop and commercialize SHP2 inhibitors, which target a key node in cancer and immune cells.

SHP2 is an important protein mediator of cellular signaling through RAS/MAP kinase pathway. Many tumors have genetic mutations, driving abnormal cancer cell growth which relies on SHP2 activity. SHP2 also plays a key role to control cytokine production and immune cell response. Therefore, inhibition of SHP2 is believed to have dual effects by potentially reducing cancer cell growth and modulating immune responses to generate anti-tumor activities. Jacobio's early clinical stage SHP2 assets, JAB-3068 and JAB-3312, are oral small molecules designed to specifically inhibit SHP2 activity.

"Identifying promising new targeted approaches for solid tumor patients is a high priority for us," said Mohit Trikha, Ph.D., vice president and head, early development oncology and Bay Area site head, AbbVie. "Jacobio's SHP2 program has the potential to treat cancer patients across many tumor types. By targeting a key node in both cancer and immune cell signaling pathways, SHP2 inhibition, both as a monotherapy and potentially in combination with other agents, may rapidly advance new treatment options for cancer patients."

"We are excited to expand our efforts in global development of delivering breakthrough innovation to not just Chinese, but global patients with cancer," said Yinxiang Wang, Ph.D., CEO and Chairman, Jacobio. "We look forward to a productive collaboration with AbbVie focused on rapidly advancing this novel SHP2 first-in-class therapy as a new approach for multiple cancer types. I am confident that this partnership will strengthen our R&D capabilities and ultimately bring benefits to cancer patients."

Under the terms of the agreement, AbbVie will be granted an exclusive license to the SHP2 portfolio. Jacobio will continue to conduct early global clinical trials of JAB-3068 and JAB-3312 with AbbVie covering R&D expenses. Upon completion, AbbVie will assume global development and commercialization responsibilities. Jacobio has an option, exercisable before the initiation of registrational trials, to exclusively develop and commercialize the SHP2 program in mainland China, Hong Kong, and Macau. Financial terms were not disclosed and the transaction is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act.

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Relay Therapeutics Announces a Worldwide License and Collaboration Agreement with Genentech for RLY-1971

December 14, 2020

Collaboration brings together clinical stage SHP2 and KRAS G12C inhibitors

Relay Therapeutics will receive $75 million upfront and is eligible to receive an additional $25 million in near-term payments and $695 million in additional potential milestones, plus royalties on global net product sales

[moneymunch] 02/4/2021 10:20

Yes indeed Bumpa, SFX-01 has been shown to directly modulate at least three unrelated mechanistic targets; Nrf2, STAT3 and more recently SHP2, all associated with multiple disease targets and all attracting huge interest from Big pharma in their therapeutic potential and all under numerous scientific research, evaluation and clinical trials and a raft of lucrative licensing deals to accelerate development. Sooner or later true and fair value will prevail, but near term it would appear the market is awaiting Prof Chalmers preliminary efficacy data from the Covid/ARDS trial...positive data will propel Evgen's prospects and potential towards global investor focus and appreciation imho. Gl ;-)

"Focus on breast cancer, acute respiratory distress including COVID, glioma and other cancers, SFX-01 has three molecular targets, STAT3, Nrf2 and SHP2."

[bumpa33] 02/4/2021 09:15

Too many people can’t look past the covid trial - because frankly all they can understand is ‘solve covid and I might get rich’.

I’m hoping SFX-01 is the key to unlock inflammatory responses in the body, period. Understand the role of inflammation in chronic disease, and then you’ll appreciate the real prize and the true scale of potential.

[moneymunch] 02/4/2021 09:14

Star-Covid19 Study

Strong evidence that Nrf2 activation is relevant in acute respiratory distress syndrome(ARDS).

The Nrf2 pathway has been found to be suppressed in lung biopsies from COVID19 patients

Sulforaphane is one of very few activators of the transcription factor Nrf2- via suppression of KEAP1, allowing Nrf2 to restore redox homeostasis, protect against oxidative stress and provide suppression of inflammatory mediators

SFX-01 is the only synthetic druggable form of sulforaphane suitable for clinical trials and was selected for the COVID study

STAR-COVID19 study is sponsored by the University of Dundee and funded byLifeArc

The study is recruiting patients with ARDS of any origin, is not limited to COVID-19 positive patients.

ARDS is a long-standing serious health problem and will remain so long after the current pandemic subsides.

Pre-COVID there were 190,000 patients and 30,000 ICU beds p.a. utilised in the USA alone

[moneymunch] 02/4/2021 08:50

Every chance that the potency of SFX-01 and its influence over NRF2 and oxidative stress could be of benefit in treating Covid/ARDS. Gla; -)