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Here's a publish of the same research from 2018.
But I think the actual research goes back further.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6216157/
I think it may be the same research that reported extended survival in mesenchymal GBM patients, though I'm not sure about this.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6216157/
And this may be the corresponding CT listing
https://clinicaltrials.gov/ct2/show/NCT01204684
I don't know why new abstracts pop up every so often, when the research is not new, though I suspect slightly different research groups are 'repackaging' the data so as to appear new.
Newly re-published, but the piece of research is a decade old, methinks...
23 patients again.
My sarcasm was in relation to the individual who blocks those who make critical comment on his Twitter feed.
(Mind you, I'm frequently sarcastic about management also.)
What's this groundbreaking news?
Do you know something that nobody else does?
That's 'in your opinion' presumably.
So now we have a product and very little upside.
When do these dilutions stop?
Nah, not really laughable.
Just a hint of sarcasm.
No, this is the infamous one.
Yes, we welcome open discussion and counterviews here, except posts that are repeated ad infinitum and beyond.
Just like he does on his Twitter feed apparently.
Well, I wonder how he sneaked that one in.
Unless he is restricted to one post every two years for now.
You wait two years to post that?
Boeing isn't up 10% yesterday, down 10% today.
It's traded in a 5% range today and ended slightly up in line with the rest of the market.
(Though I wouldn't disagree it's a target stock right now).
Well, it sure looks like concerted manipulation.
Up 10% one day and down 10% the next on zero real news.
Which F500 had a similar trading pattern?
None.
Though it used to happen every week with MNKD.
It's much easier to engineer this in a microcap.
Regardless of what you think about the shortcomings of the company, don't you think this sort of action smacks of shenanigans?
Scotty.
Your posts are obviously getting a wider readership.
TF. Just followed up on your lead.
Now I want to know who is the regulator approving the first trial of this candidate.
Whether it's the EMA or MHRA.
If it's the MHRA, then, as a UK body, they will also have an interest in doing their bit to ensure that more GMP / ATMP capacity is available in the UK.
Maybe they will expedite the inspection and licensing of any UK GMP facility that just happens to be nearly available.
Can't think of any.
Can you?
Bit more on the UK consortium that already has a vaccine candidate:-
UK gene and cell therapy group Oxford Biomedica has joined a Consortium led by the Jenner Institute, Oxford University, to rapidly develop, scale-up and manufacture a potential vaccine candidate for COVID-19, called ChAdOx1 nCov-19.
According to the firm, the vaccine is one of the leading candidates currently in development globally, and is expected to be the UK’s first COVID-19 vaccine in clinical trials later this month.
The Consortium is led by the Jenner Institute, University of Oxford and also includes the Vaccines Manufacturing and Innovation Centre (VMIC), Pall Life Sciences, Cobra Biologics and Halix BV.
The Jenner Institute and the Oxford Vaccine Group have recruited individuals aged 18-55 from the Thames Valley area in the UK to study the vaccine’s safety and efficacy.
Oxford Biomedica will provide access to its large scale GMP manufacturing facilities for viral vectors, including its new Oxbox facility, to the Consortium as required, which, along with other manufacturing partners in the UK and internationally, would allow for up-scaled manufacturing capacity if necessary.
The Oxford vaccine candidate has been shown to generate a strong immune response from one dose and it has demonstrated a good safety profile in pre-clinical and clinical trials conducted to date.
“While our current activities on this vaccine candidate are just initiating, should the Consortium confirm there is promise for this candidate in the clinical trial initiating this month, we will play our role within the Consortium to scale up manufacturing as fast as possible. This will help to provide significant access to the vaccine candidate for further clinical trials and potentially, if approved for use, for many people in the UK and beyond,” noted John Dawson, Oxford Biomedica's chief executive.
http://www.pharmatimes.com/news/oxford_biomedica_joins_consortium_for_promising_covid-19_vaccine_1337937
Very incisive analysis, Scotty.
Good spot, Truthfan.
Amazing that Cognate should acquire Cobra with their viral vector experience and capacity already in place, at just the right time!
(Admittedly it's looking ahead about five steps, but if some of the unused part of Sawston was re-purposed in a similar direction, NWBO would probably accrue considerable benefit.)
That's an interesting finding, HB.
Until there is widespread antibody testing, in any given country, it's anybody's guess to what extent the virus has penetrated to a wider community of citizens, who hadn't previously been part of the statistics.
And that will be those who were completely asymptomatic, or those who recovered from mild symptoms and either didn't get tested or for whom testing was unavailable.
What we're effectively talking about is the possibility of the virus becoming semi-endemic.
Which is not necessarily a bad thing in the long run (or at least until an effective universal vaccine is available to all, which is years away..)
Though it's an imperfect science. S Korea has reported individuals who recovered from the virus only to present again with active symptoms some weeks later.
And the antibody test is not as reliable as the infection test, I've read.
Anyway, the above is just one of the things that you have to have a handle on, before you can relax restrictions.
Another one is an effective treatment protocol. Of course all sorts of miraculous treatments are now being touted. But most haven't been through clinical trials, or haven't even been tested on human subjects, and are unapproved.
But, chloroquine / hydroxychlorine are long-standing approved drugs that just need repurposing. And it bugs me no end that the UK is still not authorising their off-label use.
A randomised trial in China demonstrated their benefits and safety for Covid-19, and there is also evidence of their benefit in previous virus outbreaks.
Lots of countries are trying to hang on to their own supply, and some have introduced export bans, including India and Belgium and there are probably quite a few more doing the same. I note that the US ordered a large amount of chloroquine just before India introduced an export ban and is trying to get India to release the order. India is one of the biggest manufacturers of the drug.
And I certainly wouldn't blame India for taking measures to look after their own citizens, when they may be just at the start of a local epidemic. Chloroquine has the advantage of being cheap, and no Big Pharma will make any big bucks on it.
Plus for acutely-ill patients with systemic inflammation, whether you call it CRS or cytokine storm, or SIRS, Tocilizumab is already approved for the rapid effective treatment of CRS that arises after Car-T treatment.
And now we have the SITC calling for its availability and use for critically-ill Covid-19 patients. That's what the BBC should be reporting, but not a word of it.
So we have the UK looking like the only country still disallowing physicians from off-label use of any approved repurposed drug.
And when I look at the total cases to total deaths ratio (not exactly the same as mortality rate) and I see that the UK is running at about 11%, I'm not really surprised.
So again, unless and until the UK gets on board with a treatment protocol that allows for use of these re-purposed drugs, they won't be able to begin to prudently relax current restrictions on movement.
I believe in the US, physicians have fairly wide discretion to use off-label drugs, and were using chloroquine even before the FDA officially sanctioned its use, as we know.
Thankyou m2p.
Thanks HB.
When I get to the virtual log-in, and am met by the Guardian of the Portal (tall guy, virtually 2mtrs, all dressed in Black), if all else fails, I shall try:-
"May the sauce be with you" (without the quotes, capital M, rest lower case).
That should work.
My understanding is they are going to apply for some type of accelerated approval in the UK.
I never get proxy papers from my Uk Broker.
Thus I doubt I will get access.
I guess it's possible that an 'in advance' log-on will allow a manual check of your name and email against company records and perhaps once verified, you will then be able to gain access again on the day.
And there is possibly two levels of access.
One that allows only one-way audio from the meeting, and maybe another that allows a degree of two-way participation.
It's all a bit uncertain, but hardly surprising really given the circumstances.
In any event, I think it's great that the advance question submission has allowed the company to pretty accurately know what is currently of most concern to shareholders (if they didn't know already, which they probably did).
Sorry GGB.
It was just my way of playing up the reference to 'virtual'.
Which I generally take to mean not actually 'real'.
In the UK, the world's greatest steeplechase the Grand National (familiar to any horserace fans or US oldtimers who remember 'National Velvet') was cancelled this year due to the virus.
So the broadcaster, along with the bookies, created a 'virtual' version, and it was broadcast last Saturday. Lots of cartoon horses and jockeys going around Aintree! And there was a winner.
It was all supposed to be based on genuine form analysis.
But it wasn't real.
But I'm hoping our ASM will be real, even without attendance, and using some sort of teleconferencing.
And did I see an official reference to it being a 'virtual' ASM?
I've already identified some of the key players with certain CGI characters...
I've clearly got too much time on my hands right now.
It crossed my mind as to whether it would be made available / offered to Boris Johnson, and my immediate second thought was; if it's made available to him, it should be available to anyone else in the UK in the same clinical condition.
I will take a look, Idunno, thought I note that link is the company promoting its own product.
But from their blurb, they do appear to be making a case, and it would appear others are beginning to look at it.
So I certainly wouldn't dismiss it out of hand.
But the thing about the anti-IL6 that I referred to, is that it's use in Coronavirus critical cases is already being advocated for by the SITC.
And you really couldn't get a body with more reputational eminence (certainly more than certain regulators imo, dare I say..).
And they would not state such a forthright view without it being arrived at by their international expert advisory board.
Plus, the SITC is the Society for Immunotherapy of Cancer, and it's really interesting that the field of cancer immunotherapy will likely play a part in identifying the treatments that could mitigate the consequences of the Coronavirus epidemic, and it brings it back home just a (little) bit closer to NWBO.
So I'm not entirely off-topic!
Don't really get what you're saying, Ex.
An RA sufferer who regularly receives Toci should presumably carry on doing what they're doing. I don't see how such an individual would have a new risk added on. Unless they also thought they might have coronavirus. Toci is ID or IV. IV would definitely be pretty difficult outside of a clinic/hospital setting.
I guess if an RA patient who regularly uses prescribed Toci might possibly already be sanctioned to self-inject, but I doubt it.
So, in reality, I can't see such an individual putting themselves at additional risk.
There is an issue with private individuals trying to get hold of Chloroquine / Hydroxychloroquine and self-medicating, because they think they might have Coronavirus, or they think they might have been exposed to the virus, and that really should be discouraged, because of hoarding, black markets, counterfeit versions, and people taking the variant intended for fishtank cleaning!
That's why Trump calling it a potential 'gamechanger' is not really helpful, because it leads to the above...
But then use of 'gamechanger' in relation to any drug is rarely justified.
But, I doubt that will be a significant issue with Toci, which is not widely available, and really can only be administered in a proper clinical setting.
So we have two different scenarios. And in respect of Chloroquine / Hydroxychloroquine, I agree that self-sourcing and self-medication comes with problems.
But I don't think that applies to Toci.
Unless Donald starts holding forth about that in gamechanger terms!
You can't stop someone who just happens to have a box of Chloroquine tablets in the cabinet, from using them without guidance.
But they won't have Toci.
As is the case with chloroquine / hydroxychloroquine toxicities, tocilizumab known toxicities (other than infection) for its main approved indication (rheumatoid arthritis) are generally associated with long-term use .
See here:-
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178374/
Far be it for me normally to advocate for a drug to be made available expeditiously (a BP one at that..), but these are not normal times.
The over reaction of the immune system might kill you in COVD-19, but turning it down makes you more vulnerable.
3.2.1Monitoring for CRS. CRS is an expected toxicity of CAR-T cells, related to the mechanism of action of the therapy. In clinical trials, incidence has been reported as being as high as 93% with a median time to onset of 2-3 days (range 1-12 days). Any organ can be affected by CRS. Diagnosis is based on clinical signs and symptoms. The following table lists common signs and symptoms associated with CRS:
Table 1 -signs and symptoms associated with CRSPyrexiaChillsTirednessRenal ImpairmentCardiac failureHeadacheTachycardiaMalaiseCardiac arrhythmiasTransaminitisDyspnoeaNauseaHypoxiaDiarrhoeaCapillary leak syndromeHypotension
Based on existing algorithms for grading and management of CRS, patients with moderate-severe CRS will require urgent treatment with tocilizumab (refer to relevant SOP(s) for management of SOP / use of tocilizumab). See section 3.3 below.
And:-
3.3 Availability of tocilizumab. Prior to any patient receiving their CAR-T infusion, pharmacy must ensure that at least four doses of tocilizumab are available on the ward where the treatment is to be administered. Consideration should also be given to ensuring that there is an additional supply of the drug available in a designated emergency/out of hours refrigerator. All pharmacists providing an out of hours service must be aware of the potential need for tocilizumab out of hours and understand the requirement for the drug to be provided in a timely fashion
SITC push for emergency/compassionate use of Tocilizumab for acutely ill Covid-19 patients.
Interesting that the experience of those in the cancer immunotherapy field will likely inform best treatment of critical Covid-19 patients.
It's well known that Car-T treatment can cause a Cytokine storm (and so can ICI's) and that is why countries that approved the Car-T therapies also approved the anti-IL-6 agent Tocilizumab.
And now SITC has come out and stated the following:-
The hypoxia and profound inflammatory response associated with the pneumonitis observed with the SARS-COV-2 virus responsible for the recent COVID-19 pandemic has overwhelmed intensive care facilities in the epicenters of infection including Wuhan, China, Northern Italy, and in the United States, the Seattle and New York City areas. The Society for Immunotherapy of Cancer (SITC) stands along with and supports our colleagues in emergency departments, intensive care units and inpatient wards in the global effort to overcome this unprecedented pandemic. It is becoming apparent that the “ground glass” infiltrative appearance seen on CT scans from COVID-19 patients with pneumonitis is reminiscent of imaging from patients with immune checkpoint inhibitor (ICI)-induced pneumonitis [1, 2]. Additionally, elevated IL-6 is a hallmark inflammatory signature seen in serum of patients with severe COVID-19 acute respiratory distress [3]. Many of us have experience with the administration of immune-modulatory agents, which is why the cancer immunotherapy community is poised to contribute to the current fight against COVID-19.
One possibility is to encourage the use of IL-6 or IL-6-receptor (IL-6R) blocking antibodies like tocilizumab (Actemra, Roche-Genentech), sarilumab (Kevzara, Regeneron) and siltuximab (Sylvant, EUSA Pharma) that are FDA-approved for various conditions including rheumatologic disease and the lymphoproliferative disorder Castleman’s syndrome. These agents could be used on easily and immediately available compassionate use protocols that could be approved on an emergency basis by all institutional review boards (IRBs) around the world for critically ill patients with COVID-19-induced hypoxia. Tocilizumab also is already FDA-approved to manage cytokine release syndrome (CRS) in patients receiving chimeric antigen receptor (CAR) T cell therapy [4, 5]. In addition, tocilizumab has been shown to reduce toxicity in patients treated with immune checkpoint inhibitors (ICIs) who were steroid refractory [6], and has been added to the ICI agents ipilimumab and nivolumab in an ongoing US phase II study (NCT03999749) to ameliorate immune-related toxicity. In Castleman’s disease, a lymphoproliferative disorder caused by Kaposi’s Sarcoma Herpesvirus, a pathogen that produces viral IL-6, tocilizumab has been shown to reduce viral loads [7]. Tocilizumab is also being explored as a potential supportive care measure for the management of CRS in cancer patients treated with a number of CD3-based bispecific molecules. Now, data from the frontlines of the pandemic indicates that the agent may offer lifesaving benefit for COVID-19 patients with respiratory distress.
Emerging evidence suggests that high levels of CRP and IL-6 are observed in patients infected with COVID-19 [1, 8]. Anecdotal experience on the use of tocilizumab at doses comparable to those used for the management of CRS from investigators in Italy [9] and from China [10] has reported rapid improvement in both intubated and non-intubated patients. In these reports, expeditious administration of anti-IL-6R therapy for patients in acute respiratory distress has been critical. A recent study protocol to evaluate the efficacy of tocilizumab in COVID-19 induced pneumonitis accrued over 300 patients worldwide in less than 24 hours. Additionally, Genentech will also provide 10,000 vials of tocilizumab to the U.S. Strategic National Stockpile [11]. Tocilizumab was also approved in China in March 2020, for the treatment of patients with COVID-19 with serious lung damage and elevated IL-6. Sponsors, investigators, and regulators have moved with unprecedented speed and collaboration to initiate protocols to formally study the safety and efficacy of antiviral agents and vaccines, as well as various anti-IL-6 antibodies in patients with COVID-19. In the US, a trial of sarilumab in the COVID-19 setting is ongoing [12].
Although randomized data definitively showing that IL-6R blockade benefits patients with COVID-19 induced pneumonitis are currently lacking, we propose that an effort should be made to maximize the availability of anti-IL-6 agents, including tocilizumab and sarilumab for use on a compassionate basis to critically ill hospitalized COVID-19 infected patients during this extraordinary situation. In addition, consideration should be given to focus efforts on rapidly expanding the ability of clinicians and clinical investigators to access investigational anti-IL-6 agents, in particular for those agents where Phase 1 and/or Phase 2 studies have been completed, and acceptable safety has been demonstrated. Even if the primary impact of a single dose of these drugs is to accelerate recovery and get patients off ventilator support and out of the ICU more rapidly, this could significantly decompress our severely over-burdened healthcare systems. We suggest that straightforward parameters including complete blood counts and differentials, serum LDH, ferritin, CRP and IL-6 be recorded in treated patients, that serum be retained for future analyses, and simple clinical parameters be assessed including time in ICU, days of hospitalization, and pulmonary parameters including FEV1 (for non-intubated patients), Fi02, PaO2/FiO2 ratio and type of oxygen supplementation need be recorded pre- and post-anti-IL-6R therapy. A simple compassionate use protocol could be assembled from existing templates, and all efforts should be made for emergency approval of the use of IL-6R blocking antibodies by local IRBs within 24 hours of the request being made. Additionally, consideration should be given by pharma and biotech to redirect the use of facilities and increase personnel involved in drug manufacturing and those serving as liaisons to the frontlines to facilitate drug availability. Extraordinary times call for extraordinary measures, and SITC calls on all involved, including pharmaceutical sponsors, health authorities and IRBs, to continue to move swiftly and creatively to remove barriers and increase access to agents like anti-IL-6R drugs that may improve our care for COVID-19 pneumonitis.
A sign that the treatment is working is that the patient becomes terribly ill, with raging fevers and chills — a reaction that oncologists call “shake and bake,” Dr. June said. Its medical name is cytokine-release syndrome, or cytokine storm, referring to the natural chemicals that pour out of cells in the immune system as they are being activated, causing fevers and other symptoms. The storm can also flood the lungs and cause perilous drops in blood pressure — effects that nearly killed Emma.
Steroids sometimes ease the reaction, but they did not help Emma. Her temperature hit 105. She wound up on a ventilator, unconscious and swollen almost beyond recognition, surrounded by friends and family who had come to say goodbye.
But at the 11th hour, a battery of blood tests gave the researchers a clue as to what might help save Emma: her level of one of the cytokines, interleukin-6 or IL-6, had shot up a thousandfold. Doctors had never seen such a spike before and thought it might be what was making her so sick.
Dr. June knew that a drug could lower IL-6 — his daughter takes it for rheumatoid arthritis. It had never been used for a crisis like Emma’s, but there was little to lose. Her oncologist, Dr. Stephan A. Grupp, ordered the drug. The response, he said, was “amazing.”
Within hours, Emma began to stabilize. She woke up a week later, on May 2, the day she turned 7; the intensive-care staff sang “Happy Birthday.”
I wonder if a VR headset is required?
I didn't realise it was a virtual ASM. I thought it was a real one.
I wonder who is doing the CGI?
Pixar maybe?
If I am right I should gather with some other disgruntled investors and make a move with SEC.
Well, if you're right then your right.
And if you're wrong, then you're wrong.
If you're convinced you're right, then do what you think you should do accordingly.
Meirluc.
If DI is correct to say trial timelines are out of their hands, then what are other possibilities?
Well the regulator themselves might have taken a peak at the unblinded data a year or two back, and maybe suggested a focus on a subgroup (meth is the obvious one) and wanting a further follow-up of that subgroup. Hmmm. Doesn't really fit.
Or the regulator might have said; 'your trial will have more OS statistical power if you wait for 85% of OS events and your projected long tail will be better elucidated'.
Then the end date would be out of NWBO's hands...
Or the MHRA is following this trial and its emerging data, and plans to advise on when to unblind.
All three unlikely, but none impossible.
I do think we will get something on the developments in the UK, and that might the be topic of 'interest'
They have gradually upped their public references to Sawston in the last few months, culminating in the SEC document about the loan and what it is intended for. That might be in preparation for telling us quite a bit more.
And if we do get a surprise announcement on a big partnership, my hunch is it won't be Merck or any other BP.
I'm not suggesting at all that they have had a fundamental disagreement with the FDA or other regulator. I just said that it wouldn't surprise me if a regulator wasn't hurrying things along.
The burger will have something in it.
I just don't know what.
At least the ASM won't be delayed (choruses of 'don't be too sure!'..)
Regards.
Hi meirluc.
It would be as well to realise that one of my hypotheses is that a certain regulator, is, how shall we say, not doing anything to speed up the end of this trial and subsequent approval.
(Which is why I don't really believe that the new guidelines and flexibilities will help NWBO.)
If that regulator advised waiting for full and final OS60 figures rather than extrapolating for the last few months, then my scenario is still plausible (even if wrong!)
But if it was at least nearly accurate, I would want NWBO to tell us.
If they said 'after feedback from regulators, we have decided not to unblind until all OS60 data is in and checked' and that they will unblind one month after that, I'd accept that, as it's preferable to 'what the hell are we waiting for' and waiting indefinitely with no idea when.
meirluc, I'm not saying I'm right. If they announce topline next week, then I will obviously be wrong!
But my point really is that I'm grown up enough (for want of a better expression) to be told frankly and factually what is actually going on.
And then I can accept it as a factual reality, or choose to sell my shares and be out of here (which I wouldn't do, of course) if I don't like it.
So basically it's my way of urging them to be as upfront as they can, about everything they can.
I don't think you are correct regarding testing in the U.S. Any supportive data?
Basically agree.
But, (there's always a but...)
What if, in the SAP submission, they made a proposal to make use of comparitive milestone survival rates as part of the OS statistical analysis, and perhaps they mentioned OS36 and OS48.
And in response, the FDA or another regulator gave an opinion that NWBO might be well advised, that having come this far, there may be grounds for extending the milestone analysis to OS60 pre-unblind, particularly given the small control group and the elements of confoundment to OS represented by crossover.
If something like that happened, then NWBO would really have to wait for OS60. If a regulator advises an amendment, whether you like it or not, you pretty much have to conform if you possibly can, or your regulatory submission (BLA / MAA) will suddenly have a much reduced chance of success.
Regulators don't like having their advice ignored.
If the above scenario actually happened, then you could say that the point of datalock/unblind has basically been dictated by what the regulator had said in feedback.
Thus, in effect, things could be said to be not 100% in their control.
But this doesn't tell us what they will actually feel at liberty to divulge, when shareholders ask the question (in relation to datalock / unblind;
'What are we waiting for?!'
Though I can't see why they wouldn't disclose that they are waiting for OS60.
(Is it sufficiently material to require advance PR'ing? Debatable.)
Just opinion.
Thanks.
Yes I will try to dig a bit on this when I get the chance.
Of course, a supplementary question at ASM could be quite simply; 'How is NWBO reimbursed for UK Specials?', or even straighter to the point; 'Who pays for it?'
But they may be reticent to answer the question directly, because they cannot be seen to be promoting their supplying of what is, after all, an unlicensed drug, and obviously don't want to jeopardise things.
Damn. Forgot to vote.
If it's not too late, five votes on Number 3, please.