Replies to post #155788 on NorthWest Biotherapeutics Inc (NWBO)

[kabunushi]

The whole IA thing is water under the bridge. How easy the 'happy ever after' the publication is, remains to be seen. But I don't doubt that the publication of an analysis of the blinded data will cause quite a stir. That's why I'm pounding the table now, because I've heard enough said very publically, namely the fact that the article was accepted for publication by a respected journal and that it's due very shortly. I'm not sure of the exact verbiage but I have zero doubt what it meant, however Linda phrased it, wrt it being published in a reputable journal and that being 6-9 months from when they started the publishing process (i.e. from last June).

The iV gang all agree that such data would be meaningless wrt to getting any approval (not clear whether or not they include UK/EU/Canada in that, but FDA for sure). They all refused to even consider that any reputable journal (their term) would even publish such an article let alone that it could be an important step towards getting an AA or other regulatory approval.

Whether or not the data presentation is a slam dunk on the regulatory front or just a very important step in a still long journey very much remains to be seen. Exactly what happens to the stock then, how it plays out, how clear the road to approval will be after that, how well the market (the shorts, especially) can see just how much is changed by the article, will determine the short-term market follow-up to the initial very positive surprise when the article is published.

[biosectinvestor]

There would have been facts to litigate under that scenario. I don’t doubt there was possible discussion of what reactions meant. There was no safety halt. It was a partial halt. Patients enrolled could continue. But most importantly, I am sure there’d have been enough of a record to continue the case that was dismissed for Failure to state a claim. That is the lowest standard of evidence intended to allow cases with only a vague “scintilla of evidence” to proceed. That they could not meet such a low standard is quite telling. Doesn’t mean there were not questions, but the shorts have a view on what the medical professionals SHOULD have determined, but apparently did not conclusively determine... I think that is and was the issue. Sure there may have been discussion and questions, but there was no evidence of such conclusions being made. It must be frustrating to them, and they keep coming at the same issue on bulletin boards, Twitter, blogs and even maybe opinion columns (leading Bloomberg to need to correct an article that referred to one of those columns). But opinions and questions did not amount to determinations necessarily, and thankfully and reasonably so for all but the interests of shorts IMHO.

[exwannabe]

VuBru, though I think your post is reasonable, I see one minor issue.

The FDA halted new enrollment at initial screening (which is also when they sign the consent), not randomization when the treatment begins. If they thought there was possible harm, they likely would have stopped allowing those already screened to begin treatment.

A near identical version of your sequence is if the FDA's hold was because patients were no longer able to give proper consent to enter the trial. The consent form spells out that they are volunteering to provide data on PFS. Once PFS is messed up that consent was invalid.

So LP tried to work work the FDA for a while before giving up on this and just cutting the trial a bit short.

This would explain both why she hoped the hold would be lifted shortly, and why she said it not might be bad (as a change to OS would be good).

[Dan88]

Unlikely though the theory has been around for a long long time as those without shares by their own words were eagerly pointing this out as a possibility, and after some time "a fact", and happy to repeat at any moment they have had, contradicting an apparent flaw: if an interim analysis, if it were conducted at all, showed no effect in terms of PFS for whatever the reason, and the DMC thought it would be futile to complete the trial, it might recommend the company stop the trial. While the FDA might be notified, it was non of the business of FDA if the company wanted to continue the trial since patients would not be harmed and they were continually receiving the standard of care; FDA has even had no business to impose a partial hold for the company to screen any new patients;

On the other hand, if the vaccine seemed to speed up PFS events due to reasons known or unknown, such as pseudo progressions, only logic is for the FDA to order the company to stop the trial because patients in the trial were harmed. That meant the company had had to stop administrate any vaccines to any patients pending on the company to conduct investigation which could show that reason was false. Then, the FDA might allow the company to continue to administrate vaccines. It was in essence a safety problem. In such case, the trial had to be stopped while investigation initiated aiming to approve otherwise.

We know that was not the case,

In addition, it would put the company in a position of intentionally lied when it had said twice that it had not been aware of any company-wide news or events that could explain the sudden drop of share price in a significant magnitude.

Adding on top of that is Neil Woodford November 2015 multi-ten million dollar financing deal with the company at $5.5 per share, and his now famous words "nothing untoward" in regards to company's situation at that time.

So I don't believe PFS theory at interim has any truth. Instead, I kind of believe that one or two AF like minded investigators in the trial might report to FDA about some presumably irregularities of the trial, such as record keeping, manufacturing changes thus agent changes, suspicious screening criteria for earlier and later patients, etc., considering the trial had been up and down in a period of more than 10 years. The investigator(s) might be recruited by AF or the kind, or they might be just rebellion for unknown reason.

Anyhow, FDA for whatever the reason believed it was for the best interests of patients and the cause to impose a partial halt so that the company could not recruit any more new patients, so that the company might consider to start a new trial from scratch. But the company thought otherwise, and had always believe it had the winning hand: it can at end show FDA how patients treated with DCVax-L live longer, much longer than placebo patients even they later all crossed to being treated with DCVax-L, let alone the norm, including Novocure's (NVCR) Optune therapy device.

After a long back and forth between FDA and company, FDA lifted the halt last Feb, suggesting the dispute or discord has been fully resolved since then.

So I do feel the awkward position for the company in regards to whether such information (the reason for the halt) shall be released or not.

For the integrity of the trial, the company decided it better not disclose the reason until the trial integrity concern becomes no concern. That I would think is when final data are announced, or the company can choose never disclose it, and it is perfectly fine and legal.

BTW, my current sentiment for the stock is strong buy.

[this is my one post a day restriction imposed by IHUB admin and my lack of enthusiasm of posting more]

[Ultraz2]

Very likely, and is the basis for changes the FDA has made as evidenced by the study over the last ten years, imho...they have been working very closely together is my bet...

[biosectinvestor]

It's not a single treatment. It's an ongoing treatment for patients that are sick. In this case, if the FDA actually thought it sped the recurrence of cancer enough to halt on that basis, that would be a SAFETY ISSUE. A halt on that basis suggests that the FDA thinks the vaccine is making people sicker faster. They continued enrolling patients who had not yet received vaccine. Safety halts don't work that way.

Granted, the argument that they later convinced the FDA that what looked like PFS wasn't PFS and there was an OS benefit is very possibly an actual conversation that was being had across the trial, amongst many doctors and agencies, but if there was a halt on that basis, and it was not a "SAFETY" issue, I'd be deeply surprised.

I think the conversation was occurring, but I don't think they thought it was actual PFS. I think they had an idea that it was the vaccine working, and I don't think that was likely the cause of the halt. Possible, but not likely in my estimation.

Reasonable and appropriate scientific discussion and theory to be working through as the trial was proceeding, but an immune reaction was a premise of the treatment. So of course they'd expect an immune response and be looking for evidence of it from the very beginning. It's one reason some have also said, and I believe this is true, that DCVax-L is a little weaker, because you are operating within a skull, and causing a brain to swell too much is potentially dangerous. However, there were no indications that such events happened either, to a dangerous level. If it had, that would be a safety event the company would have had to have discussed.

I suspect the halt was for entirely different reasons, but even longs have given in to the non-stop drum beat of shorts, which of course show actual things and make it seem like those actual things are a bad thing... Over time, that was resolved into it could have been a problem... and now people may accept that as the likely cause of a halt. As I said, anything is possible, even that, but I don't think that is the likely cause of the halt, or there would not have likely been other arms, and humanitarian approvals that included people like Kat. The FDA doesn't work that way. They don't approve unsafe treatments for humanitarian care while halting a trial for safety and allowing patients to continue taking an agent that may cause recurrence of cancer. There would have been a very serious set of meetings and they'd have resolved that kind of a question long before last year. Long before.