While I was on Drugs.com, I had a quick look to see if there had been any new patient reviews for a certain ICI:-

“My mother had 2 rounds of radiation for stage 4 lung cancer. Then doctor said just to be sure it doesn't come back let's put you on *******. She immediately started having fluid on her lungs. They gave her 3 more ******* infusions until she developed pneumonitis. The doctor let her leave his office with a blood oxygen level of 91. Prescribed prednisone, 60 mg. After 3 days she had to be put on oxygen, which she needed until she died. She went from being totally independent to totally dependent within 2 weeks. She had so much fluid on her legs that the blisters popped open and her skin deteriorated. She needed bandages on both legs that needed changing everyday sometimes twice a day, She got weaker and weaker. She went from walking by herself to needing a walker and after 2 months a wheelchair and 3 weeks later couldn't even get out of bed. She died 2 weeks later. This is a fatal drug with horrible, horrible side effects. Do not take this drug unless you're ready to die. rating - 0.”

The reviews for both NSCLC and SCLC are truly appalling. Take a look..

No wonder I expect the L arm to do best in our rGBM combo trial.

'Remission rate' apparently.

The refrain from sceptics has long been that the FDA won't allow a comparison between an investigational drug and a historical control for approval purposes.
Well clearly, in certain circumstances, and on certain occasions they have done, and will likely increasingly do so. And yes, maybe a somewhat lower bar for medical devices may sometimes be in play here.

The door on this front is slightly ajar rather than wide open, I would suggest. But the FDA pretty much have the discretion to accept whatever evidence they see fit, particularly in the case of a rare disease without an effective treatment. And GBM is (currently), a rare disease. And certainly without an effective treatment.

That doesn't mean that if L has OS60 of 20% and SOC is around 5%, it is a shoe-in, because even historical controls have to be well-matched for all the variables. And you cannot simply compare outcomes for this trial population with outcomes for all GBM patients. Not even those in the US, the UK, and Germany.
But you can identify a closely matched control population, and make statistical adjustment for difference between covariates.
And yes ideally, you should have prospectively identified your historical control or controls.

If the FDA thinks that a valid comparison can be made between the L survival data and maybe the corresponding Optune survival data, there is nothing stopping them from doing so! Particularly if L demonstrates clearly superior milestone survival at all points beyond 2yrs. And if they recognise such a comparison as valid, then they may consider it as supplementary evidence on top of any in-trial comparison.

So the call of; 'the FDA never accepts historical controls' is clearly not the case.

True. Though price trends after unblind might be a little bit more indicative.

Lykiri; you are a tease..!

Well, if you can find said articles, we can take a look to see if they're worth the virtual paper they're written on.

The only thing I would say, is that there just may be some sort of expedited passage in the works, towards a UK MHRA approval after a Brexit crash out. It's a longshot admittedly, but they could pick up with a Scientific Opinion, and maybe use Specials RWE outcomes to supplement P3 data. Obviously it would need a facilitative MHRA, with a point to demonstrate.

Regarding the Brexit crashout; I am pleased to announce that my survival prepping is well under way..

You're mixing up Cognate with Advent / Toucan / NWBO.
Cognate has nothing to do with Sawston.

PIM is part of the EAM scheme. It didn't cost them much but they didn't pursue it. They never got to the Scientific Opinion stage.
Treatments under EAMs are not reimbursable anyway. So that was always a dead end.

HE. They treated 9 patients. Another dead end. Protracted and expensive negotiations with the German insurance companies. Certainly a net expenditure. They allowed the annual re-registration to lapse.

RTT. Another dead end. Enough said.

UK Specials. Very different. You need a UK Specials registered manufacturer or supplier / importer. They have that. Currently CCGTT. Will be Sawston. And a bona fide physician who makes bona fide referrals. They have that (one, maybe several). Every patient treated under UK Specials provides useful revenue. On a £250k treatment, their net income is probably £50-£70k. That would be with averaging a per capita payment to Advent (though they pay Advent whether they use them or not).

At five patients a month that would be about £3.5m a year. That is probably the max until Sawston is up and running. At a guess, Sawston could triple capacity. Then it would just be a case of whether they get enough referrals. But £10m annual net revenue (profit) is probably achievable indefinitely (until superseded by UK regular approval).
Or it was until Covid was introduced. That has totally kyboshed things in the last few months, but hopefully not for too much longer.

In summary, PIM and HE had some PR value at the time, but that has long gone.

RTT just a plain nope.

UK Specials completely different and very worthwhile.

Just asking you to evidence your assertion that:-

"NWBO did not disclose that the FDA had issued a hold until half a year later when it became available in Court documents."

I didn't even say that you were necessarily in error. I just felt it was the kind of bold assertion that should really be backed up with a source!

Don't worry too much if you can't find a supporting source... You can make unevidenced assertions if you like, though I wouldn't say it is particularly good practice.

Do you happen to know if the FDA actually make public a record of all trials for which they have ordered a hold?
I'm not sure, but thought that perhaps they did.

What we are trying to establish is whether and precisely when, the FDA issued a clinical hold order, and, if that occurred, whether NWBO failed to disclose it for 6 months, as you asserted.

That court document doesn't actually answer those questions.

They should have registered NWBOGbmH as a charitable foundation.

Charitable foundations get exemption from tax, and you can launder billions.

Still waiting on a link, Ex...

Well, we'll have to see.
I thought it was rather a curious PR to be honest. I'm not complaining, because I have repeatedly called for regular updates.
But this one kind of said:- everything is now in place for datalock, but we haven't yet datalocked.
Or words to that effect.
But they have confirmed that all the scans and bio assays are done, so it's now just a final scrub and polish.

Surely final, irrevocable, datalock is now only a week away. (Though I expect the CRO are going to want a chunky lump of payment before releasing the entire dataset.)
And only then will I breath a sigh of relief, because getting to datalock was always going to be harder than getting to a topline statement. They were dependent on so many different third parties coming up with the goods, before being in a position to datalock.

But then they have said the stat guys need a couple of weeks (or was 'several weeks' also used...?). Then lengthy consultations with their SAB and the trial steering committee...

One thing we can say; they will definitely meet the 'after Labor Day' prediction. I honestly don't really care whether they make the end of Sept, or go into Oct by a week or two. Just keep us updated as promised. Which they more or less have done.

JMO.

Ah. At last we agree. If they cannot meet their own stated timeline, then they need to update us. Which is exactly what I asked for in a post from yesterday. And previously stated on several occasions; update as much as necessary, and don't leave us in the dark.

And, unless you think we will see topline in Sept, then you never really disagreed with me anyway!!

Just being realistic.
Are you still expecting topline in Sept?

God. It must be a quiet day, if we have resorted to this discussion...

Of course I don't know.

I just think that it is more likely than not, that datalock hasn't happened, because they haven't told us it has.

Therefore, I don't think we will see topline in September.
Therefore I won't be on tenterhooks in September.

Rather I'll adopt the 'it'll come when it comes' attitude (on topline), and assume it'll be some time after Sept.

Do you really see things differently?

Just a reminder that NICE gave a positive rec on one of the Car-T's within days of that drugs approval.

They are not slower than the EMA.

In theory, the idea is to dovetail the two processes, so that NICE reports very soon after a marketing approval is granted.

I'm sure it doesn't always work as seamlessly as that. But it certainly can do, if NICE decide to prioritise, due to a recognition of an urgent unmet clinical need.

Well pgsd, if we don't get confirmation of datalock in the next couple of days, I will personally discount any real prospect of topline in September.
There is probably going to be at least six weeks between one event and the other.

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.

You think I'm joking?

Not at all.

I certainly don't expect a large company to buy NWBO any time soon.
Nor do I particularly want it either!

Yes. Datalock is due now.

I'm convinced they will tell us when it is achieved. So it hasn't been achieved as of now. But the week is still young...

If they don't achieve it this week, I would like a progress update from the company.

Which is not a problem. Following the last three updates, the market has edged up, in the following 24hrs.

Well, your reference basically concludes, in terms of making public disclosure; "It depends...".
And if they don't know themselves, when they are both lawyers, who in the hell does? Basically nobody knows. It's one of these legally arguable points, that can only be decided on a post facto case by case.

I always find it curious and somewhat ironic that the SEC will likely come after you (closely followed by a gaggle of ambulance chasers), if you fail to disclose something that is significantly materially negative, but in the case of whether you need to disclose what a SEC subpoena is about, the answer is; 'well, maybe yes, or maybe no..'

If the Board wants to continue discussing it ad nauseam and ad infinitum, then that is fine by me. It's not for an individual poster or even a section of Board opinion, to arbitrate on what should or should not be discussed!
It's just on this one, I think the discussion is likely to be somewhat circular.

Actually the debate on the legal niceties of what they should disclose or what they need to disclose, in relation to having received an SEC subpoena, is actually more interesting in some ways, imo.

As it stands, we have no idea whether it is something of limited significance (nothingburger), or something of significant significance (somethingburger). Which is why the discussion is likely to remain somewhat hypothetical and without conclusion, unless and until new information comes to light.

The company would surely be obligated to publically and accurately indicate to shareholders what the SEC subpoena was about. And unless I'm mistaken, they made no reference to it being about a late filing.
Who keeps bringing it up? Seems like posters from all over the spectrum are prepared to give voice on it.
It's the Board topic of the day, but that is all.

It's one of those topics where the discussion will be circular and not lead anywhere.

It'll all come out in the wash. In other words, a few months down the line, there will be a publically released resolution. Until then we won't know if it was a nothingburger or a somethingburger.

Can't see why it should preoccupy us too much, unless any new information comes to light.

Nope. Can't see it.
Being a bit dense today.
Another clue please.

That's the difference between weak antibodies and long-lasting T-cell memory. T-cell memory as elicited by DCVax-L in GBM, and by natural exposure to SARS-CoV-2. For GBM, the DCVax-L vaccine is necessary, for Covid the vaccine isn't!

I think that is the best you will ever hear about it!
If you define 'work' as preventing infection, then it didn't work in the animal study.

Here is an alternative viewpoint:-

Apologies; my mistake. I mean't the Oxford vaccine.

Mind you, I will blame Ex (always a good policy), because he threw me off, when he referred to 'the Cambridge monkey cough vaccine'.
Ex possibly also meant the Oxford vaccine.
Perhaps he will clarify.

(UK have thrown money at six candidates now....)

Cambridge vaccine didn't work with the macaques. No reason why it should work in humans.
Your Govt has now thrown another $1.6B at a different candidate; namely Novavax.

Yes. It has become de rigeur to have some identity symbols in the background when you're doing that Doom teleconferencing lark.
I guess some with letters after their name have earned the right to a full bookshelf. It fits with the 'following the science' mantra.

Like you, I go full screen and try and identify titles!
Lots of scope for subliminal messaging I guess.
Personally, seeing as I am several volumes short of a full bookshelf, I would probably opt for some nice 60's era European art ceramics, and perhaps a few old Beano annuals.
Yes, my mention of lights going out and winter nights and books was indeed a reference to their combustible value.

I found it particularly galling when the UK government spokespersons gave their daily Covid briefings standing at a goddamn lectern with several almighty big Union Jacks in the background, at the same time as announcing various crazy measures that will take us well on the way to national economic and social collapse.

The biggest mystery about the markets in general, is how and why they are holding up, at the same time as economies are already in unprecedented recession with a deep and sustained depression to follow.
Pharma is a bit of a special case, because they are having billions thrown at them by Western governments (as if they needed it..) for anything with a Covid connection, leading to a sort of feeding frenzy by speculative investors. Even that can't last.
Fauci and Gates are now telling us that the lead vaccine candidates basically don't work, with Hahn talking about just '50% effectiveness' required for approval. You're looking at short-lived symptom reduction at best. And at worst... well, I won't speculate here, beyond the well-known risk of disease enhancement.
(GAVI talks about their global agenda of overcoming 'vaccine hesitancy' Well I won't hesitate at all in saying 'thanks, but no thanks.)

When the vaccines (that Govts have sunk billions into) fail, then the same Govts will be told; 'you need to help fund us to develop mAb's, because they are the only way forward'.

Here is the NIH and NIAID preparing the ground:-
https://jamanetwork.com/journals/jama/fullarticle/2767383

Which brings us to gold. A gold tracker is probably a reasonable medium term safe harbour for the average guy. And it's ethical neutral imo.
But in the longer term, even gold will likely lose its traditional relevance.
Burning books has a certain utility if you want to deny history or keep warm, but you can't eat gold!

If AV hadn't made his post, I doubt everything else would have subsequently transpired.
Virtually nobody would have been aware of the good (?) Dr's comments. They've probably been out there for yonks.

Did AV, by bringing it to our attention that some random doc gave a pessimistic view about the trial move the market? I doubt it, but you never know.
Surely the drop was more about the financing.
I do find it amusing, because I'm sure AV didn't expect the rest to transpire. And I can't get uptight about anything to do with NWBO, because there are other things in the world to get uptight about right now.
I do maintain a high opinion of Al Musella, because in a world of mercenary types, I believe he is not in anybody's pocket, and he genuinely just wants to improve the treatments and outcomes for GBM patients. He would never make a politician! Well, not of today's type anyway.
I know he doesn't think L has failed, and indeed holds high hopes.
There are loads out there with a vested interest in L not succeeding, but one more conflicted Doc doesn't really make a lot of difference.