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I don't think they are going to damp squib us with the late breaker.
Up until this development, I expected a somewhat ambiguous topline, one that posed as many questions as it answered.
But now, I can't see why we won't get a reasonably comprehensive report on outcomes, which will be positive in relation to the revised endpoints. And a stated firm intent to go straight forward with regulatory submissions in at least two jurisdictions.
All to be fully fleshed out shortly after in a top notch journal such as JTM, guaranteeing open access worldwide!
(They shoud avoid those shady journals like the Lancet and NEJM...)
Hey Abeta.
That's a very timely reminder of future potential.
Regards.
Ah, very good.
If that is the case, we should be way over the dollar.
Thanks.
And thanks to Anders.
Well...
Just catching up after a bit of a sabbatical.
EU Trial Database for MHRA:-
"The primary endpoint of this study is overall survival (OS) compared between patients randomized to DCVax-L and control patients from comparable, contemporaneous trials who received standard of care therapy only, in patients with newly diagnosed glioblastoma."
This suggests (as many have noted) that the MHRA are accepting of amended endpoints and will entertain historical comparisons.
EF-14 is the obvious comparable, contemporaneous trial, but certainly not the only one.
And in the case of the Optune control arm; well, it performed pretty damn badly in EF-14 (5% survival at 5yrs), which was fortuitous for Novocure at the time, but is even more fortuitous for NWBO...
It represents such a low bar that DCVax-L could only fail to clear it by accidentally tripping over it.
If we expect OS60 of L treatment arm to be ballpark 21-22%; well, that's a rather large 430% better chance of making it to 5yrs compared to Optune control. And it will be also superior to Optune control at earlier milestones, but obviously by somewhat smaller margins. I haven't looked at comparative median OS yet.
Stupp 2005, when the treatment arm added chemo to rad and became SOC, achieved 9.8% OS60, iirc.
But you are still looking at more than doubling OS60.
First secondary endpoint not so clearcut, because we simply don't know how effective L can be, when produced from original resected tumor but not employed until time of disease recurrence. And we have a much smaller sample size (approx 69 who crossed over?).
But I would still expect a comfortable statistical 'pass'.
Second secondary appears to be 'adjudicated' PFS.
Easy win..
Third secondary appears to be 'unadjudicated' PFS.
Wouldn't like to say on that, because the degree of confounding pseudo-progression is an unknown (to me at least).
Haven't given much thought to secondary (iv) and secondary (v) as yet, because the game will surely already have been won.
Unless I'm missing something, the German PEI version of the EU register still shows the original endpoints, with PFS as primary, and OS as secondary with no reference to historical controls. And the stance of the PEI may in fact be the current EMA stance....
Maybe.
So I am only able to conclude that it is the MHRA that have accepted the complete endpoint overhaul.
And possibly nobody else. At this stage.
Unless I've missed something, which is possible because I haven't yet read most of the last 1000 or so posts.
On the face of it, UK approval would now appear to be somewhere between very likely and very very likely. A small caveat on the whole meth / unmeth issue.
And I would expect an early positive NICE recommendation, because I think the quality-adjusted life years gained will stack up OK on the value front. Maybe after a little bit of price point negotiation.
(Which, dare I say it, fits with my previously expressed idea of the MHRA wanting a 'marquee' approval after Brexit, to demonstrate how they are able to reach expeditious approval decisions).
All very encouraging. And other regulators would be very likely to fall in line with approvals within a year or two, even if they are not currently accepting of the endpoint overhaul. Because otherwise you would have large scale medical tourism into the UK, which would make the FDA and perhaps the EMA look a bit silly, as time goes by. Maybe they will settle on some form of Phase 4 trial on clinical outcomes in the UK.
And if a UK green light is forthcoming, it would be a very significant validation for the whole DCVax platform and its future potential.
(Initial approval is always the hardest.)
Thus making it more of an attractive acquisition target.
Which won't do the share price any harm..
Not that I expect LP to step aside any time soon...
Hope I'm not jumping the gun here, and I haven't missed anything.
But on the face of it, things are now a lot rosier in my opinion.
(Assuming the UK doesn't completely self-destruct on the Covid front in the meantime.)
I will try to oblige at the right time.
I only indulge in a bit of self-back-patting every now and then. It could get a bit repetitive and monotonous, if I did it all the time.
And as you say, it's a prime cause of musculo-skeletal injury.
Ah, CD. So true.
But I believe in evidence-based medicine, rather than rent-a -model!
Just hope they steer clear of Neil Ferguson...
Regardless of whether they are obligated to PR datalock, why wouldn't they?
What purpose would it serve, other than keeping shareholders in the dark?
So I still reckon they will.
If I was in their shoes, I would want to put the flags out and tell the whole world!
It is fairly momentous, both for themselves, everyone associated with the trial, and for longstanding shareholders, seeing as it marks the end of the, ahem, lengthy trial, and the end of a long journey (even though the data analysis would be yet to come).
Not that I expect any big market move following such an announcement.
It would insure the FDA sees the changes as post hock* garbage.
*post hoc
I'll let the 'insure' go...
Yes, I'm just being annoyingly pedantic as usual, Senti.
LG has said 30 did not receive L a couple of times recently.
So it's 232+69+30=331.
About 90% of the entire trial population ultimately received DCVax-L, 238 - early, and about 67 - late.
Good for you.
JD. Are you now ahead on paper?
If you don't mind me enquiring.
1,400,000,000 shares = no upside.
It's a fact that cancer drugs frequently end up in the NCCN guidelines as recommended treatments for indications other than those for which they were approved. It happens.
Probably because nearly all the NCCN writers receive some form of remuneration from a pharma company or companies. And if the drug is recommended in NCCN, it becomes de facto SOC. And generally gets Medicare / Medicaid coverage.
I'm not suggesting that L could suddenly be widely used for a range of operable cancers, because it couldn't.
But it might be approved for ndGBM, yet end up also being used quite widely for recurrent GBM as well. That sort of off-label use is not much of a stretch at all.
Not that this sort of thing is necessarily good per se...
A point made by Vinay Prasad:-
Prasad: On a single day in March 2016, we froze the entire FDA drug approval list, and we gathered the entire NCCN 4,000-page document and froze it, as well. We compared these two documents and, in the month that followed, we painstakingly compared every time a drug was mentioned and how many times it was recommended by NCCN.
Q: What did you find?
Prasad: The first thing we found was that FDA had approved these new drugs for nearly 70 indications. Then we saw that every single indication the FDA had approved the drug for was in the NCCN document. It missed nothing. In addition, NCCN recommended another 40 or so indications for which these therapies were not FDA approved. We then asked what the evidence was for those 40 or so additional purposes. In most cases, NCCN offered no evidence. In some cases, the evidence was very weak and came from uncontrolled clinical studies.
Q: Did your findings surprise you?
Prasad: We were surprised that NCCN was recommending these drugs so often beyond the approved uses, and we were surprised that the evidence cited was poor, or that evidence was not cited at all. In the United States, we have a system in which officials are stating they are going to pay for all of these cancer drugs that are recommended by experts. Those experts are going to be recommending them beyond what they have been approved for and they are not going to tell you the evidence that they are citing to recommend them, or there is no good evidence, and you have to pay for them once they recommend it. The other thing that serves as sort of a backdrop for this is that many of the experts on the panel have financial ties to drug makers. When putting all of this together, we have to ask ourselves if this is the optimal system. The whole picture is what is concerning. There is the potential for bias here.
I'm sure there will be a doctor somewhere who might use it as a last resort, maybe for a patient with brain mets. If you were in that position and had the funds you could probably find a doctor to so prescribe. And if a miracle happens, you become a case study.
Although that is a long way short of a broader label extension.
I think their adds on 5 year OS of "complying" patients is pure crap. Post hock cherry picking is easier than finding Easter eggs in a lawn sowed for 3 year olds. The FDA should smack them, but they are still licking wounds from lawsuits like AMRN's.
Many of the fudsters on this board are supporters of this supposed treatment and Dr. Stupp's final slide which was “A new cancer therapy has been born.”
It's really astonishing to see just how powerful the force of confirmation bias really is. People see a posting for a presentation at SNO that looks literally exactly like every posting for a conference this company has ever made, and they immediately assume that not only is the company presenting Top Line Data (even though the posting mentions nothing about TLD), but that the company is presenting positive Top Line Data!
Case Presentation about Brad??
Rising incidence of Brain Cancer.
Yep, it's happening pretty much everywhere in the developed world.
In France it's quadrupled in 30yrs.
https://www.phonegatealert.org/en/press-release-brain-cancers-4-times-more-new-cases-of-glioblastoma-in-2018-according-to-public-health-france
Up 500% in Malta in 10yrs.
https://www.cureus.com/articles/31024-rising-incidence-of-glioblastoma-multiforme-in-a-well-defined-population
Denmark and UK doubled in 10yrs.
https://ehtrust.org/scientific-documentation-cell-phone-radiation-associated-brain-tumor-rates-rising/
Obviously reasons for the rise are multifactorial. And it's a huge hot potato to point the finger in certain directions...
But it sure isn't going to stop rising.
NWBO may design more integrated flaskworks with inputs from computers so the personnels don’t need to walk too far. Every human steps counts reducing productivity.
Yes, but this was competitive tendering for a loan from a Development Fund with limited funds to dish out. And NWBO won out!
(I'll brush over the fact that it wasn't 0% interest and it is a secured loan...)
I wonder if you have affiliation with the vendor because you mentioned crab cakes a lot.
Presumably that is when we get topline, or even a fleshing out of an earlier topline.
That's a date for the diary.
https://www.eventscribe.com/2020/SNO/fsPopup.asp?efp=S0taQ1hBSFkxMTYzNQ&PresentationID=772799&rnd=0.2810788&query=Dcvax&mode=presinfo
For those who do not get it, "may" is indicative that they do not yet see proof of extended survival.
Hmmm. 'Final contract negotiations'
So it may be back on soon with a new sponsor arrangement.
How else are you going to deal with adaptive resistance*?
PGSD. I don't rule out a BP buyout either. But a buyout by a BP to nurture Direct to an eventual approval? Ain't gonna happen (imo).
Especially a BP that has mucho existing revenue from a checkpoint inhibitor.
You could see the recent acquisition of Flaskworks and bringing that proprietary DC manufacturing process in-house (along with its developer), as a sign that LP wants to retain the independence and autonomy of NWBO for a good while yet.
That's the way I see it anyway.
I think the consortium that backed the Cognate management buyout, and then invested further for Cognate to buy out Cobra Biologics, could well be a candidate to take a stake in NWBO at some point down the line. And if that transpired, it would be OK with me.
Being a long-haul investor, I really don't want a lock, stock, and barrel buyout anyway. And the signs (that I see) are that LP intends doing quite a bit more 'hauling' yet.
JMO!
Regards.
I'm aware of these.
Yes, they are further reasons why Merck wouldn't buy NWBO.
Wise words, CD.
But I will still breathe a sigh of relief when datalock is confirmed.
I also owe you a more extended response to an earlier post, which I will get around to eventually!
I know it's a correlation and not necessarily a causation, but do you mind not washing your socks indefinitely, maybe for a year or two, or until they stand up on their own?
Flaskworks appears to be mainly one guy; Shashi Murthy. And he (I'm assuming he is a he) is clearly the scientist behind the development of the Flaskworks semi-closed system for DC production.
You don't get much for up-front cash of £1.65m these days. But LP knows a potential bargain when she sees one (witness real estate), so let's hope this turns out to be 'a pennies on the dollar' deal, as time goes by.
The 'technical team' that has joined NWBO is probably quite a small team as teams go. Somewhere between 1 and 2 (and probably nearer the former..).
The technicalities are largely beyond me. I don't know whether the micro-Den cartridge system was dropped by Murthy or just dropped by Corning, so Murthy decided to take it elsewhere. I don't know whether the bioreactor replaces perfusion-based micro-Den or employs it.
Is it a niche application? Of course. But it's a niche that's only going to get bigger. The whole CGT field is a burgeoning one.
But having this proprietary process and its technical specialist on board and in-house now, can only be seen as a massive plus in my book.
LP is no doubt acutely aware of the costly limitations of the largely manual DC isolation / maturation process that bedevilled Provenge, so is taking the necessary steps to reduce manufacturing unit cost, improve reproducibility, and reduce human error. And ultimately reduce the therapy price tag. This will all help down the line when HTA's, (notably NICE) look at accrued patient benefit in terms of QALY's in their cost / benefit analyses.
If one is looking for a multi-billion buyout to occur in the next few weeks, then this development has little relevance.
But for long-haul investors (such as myself), it's a very positive development, and is another demonstration of LP being ahead of (or at least up with) the game. She knows that all of this is an essential plank that has to be in place for approval..
(UK first??)
Here's a link to discussion about CGT process development coming out Phacilitate 2020, which just happens to feature both Mark Lowdell and Shashi Murthy :-
https://bioprocessintl.com/manufacturing/cell-therapies/discussions-at-phacilitate-2020-on-cell-and-gene-therapy-products/
And here is a link to grant-based seed-funding that Flaskworks has received in the last couple of years, which obviously contributed greatly to their process development.
From which:-
This project will address this major unmet need by leveraging advanced concepts in engineering and biology to design an integrated system for cost-effective dendritic cell therapy manufacturing. Given the large number of personalized cell-based therapies currently in clinical trials and recently approved, such a system is expected to address a major societal need and have significant commercial potential. This SBIR Phase II project will advance to commercialization an advanced bioreactor system for closed-system manufacturing of autologous dendritic cell therapies. Multiple technological challenges must be overcome to automate and integrate the unit operations associated with the manufacturing of these therapies. Because of their low abundance in blood and tissue, dendritic cells are typically generated from leukapheresis-derived monocytes. Adherent monocytes must first be converted into nonadherent immature dendritic cells via incubation inIL4 and GM-CSF, prior to maturation and stimulation with tumor specific antigens. In order to achieve automation and integration of these steps on a single platform, the proposed system will build on successful Phase I work in perfusion-based dendritic cell culture that enables reduction of process steps associated with cytokine infusion and achievement of perfusion in a simple and cost-effective single-use bioreactor design. In addition, an agile product development methodology will be utilized in conjunction with computational modeling to rapidly and iteratively create prototypes and test them in the hands of potential customers.
I've always thought it was a bit of a silly stat.
But there is every reason to expect that median to move up again.
What was the CI again..?
We do know the dollar value of NWBO's assets in Sawston and it is not very much.
Yes, Doc; similar thoughts here. If the right backer comes along, it will likely be from outside of existing Pharma.
Regards.
If TLD is wonderful, great then why not?
it would be of best interest to NWBO, its management and shareholders that, after TLD or approval, NWBO will be acquired for around 6-9 billion asap by Merck.
If you want to play it big and dont want to go home then you should have your home in order. NWBO has not. If NWBO wants to wear a big player suit, then the suit should have no holes and be iron clad otherwise you will not be taken seriously.
Its those problems that will lower the take over the price for NWBO.
After Merck has acquired Im sure the Merck legal department can iron all problems and LP can retire.
Actually Im expecting this scenario. longs with SP of above
$ 10 have to think again its not gonna happen for all problems NWBO has called upon itself.