Replies to post #63576 on NorthWest Biotherapeutics Inc (NWBO)

[eagle8]

Thanks Rk,

After reading this i'm 100% convinced you are right here.

Especialy this sentence i like most ( your words, but we know already this is most likely, thanks to great research on this board) :

" Their new TFF patented methods are said to reduce their manufacturing costs".

[Know-Fear]

Nice work RK. Several of us suspected (including myself) Germany was key to the hold with various good and bad reasoning and I give more credence to your work.

[md1225]

Wow great post! I encourage all to read this post and remember NWBO was trading at 10/share prior the screening halt. This registrational trial will readout in October of this year.

NWBO is the next CPXX 1 to 40/dollars in months.

[flipper44]

It appears that if the TFF machines were integrated into the phase III trial, it may have happened both in the U.S. and Germany around late May 2014.

Additionally, as you also just posted, sometime near the end of 2015, King's College was preparing to start scaling up commercial manufacturing level capacity for European distribution -- following negotiations conducted in October 2015.

Fraunhofer also added 5 more lab spaces and it appears Cognate just scaled up as well. Maybe some or all of these expansions were for NWBO.

It seems to me TFF incorporation into the trial was in May 2014 in Germany and the U.S. (if they were indeed integrated into the trial), and following that, TFF scale up to commercial commercial capacity levels has been ongoing since Fall 2015. Perhaps.

As NWBO pointed out back in 2013, these machines save money, time, resources and improve capacity to meet global demand whilst more naturally isolating monocytes and consequently improving the purity of pre-pulsed dendritic cells to assure there is no premature activation in some cells, thus improving overall potency per volume.

(All this occurring at such time that DCVax-Direct manufacturing capacity presently is apparently installed in Sawston.)

If such preparations did/have in fact occur(ed) along these timelines, it may very well be that the last few patients "enrolled" will have their autologous material processed through the newly installed commercial level capacity systems as opposed to the trial level capacity systems -- even though since May 2014, the TFF system (at a trial capacity level) might have been part of that trial system. If so, than any continuation of the trial may have, as you say, "reserved" patients to enroll later to test the newer equipment, but I suspect that if this is the case, they will enroll the last few in all three locations (not excluding Germany). If the trial is succeeding....running those last patients through (if that is necessary) might be more related to safety precautions, meeting release criteria and GMP rather then further long term trial outcome related to efficacy determinations for the phase III trial.

NWBO has, in the past, efficiently suggested overlap between trial and commercial infrastructure is necessary to make the transition to full scale commercial capacity. Perhaps we are seeing yet another way in which this philosophy is applied. JMO.

[doingmybest]

RKMatters, I will review the CTU link when more time is available over the weekend, but, at a quick glance it does not look like a manufacturing entity but a clinical trial services entity, providing some CRO type of activities.

[Pyrrhonian]

Wow, you put a lot of work into that!

Look, you just don't change process after 300/348 are randomized. Or any significant number actually.

Manufacturing issue was a viable guess as to the cause of the hold at one point. Though I never really bought it as they had gotten so far for so long without any issues, and even had the very thorough PEI vetting for hospital exemption. That's extensive, and Frau passed the test, with tech transfer and process exactly as done by Cognate. Suddenly Frau fails out of nowhere? Or Cognate suddenly fails after making that many vaccines for years? It just never sounded right to me.

"The Company (NOT regulators) stopped screening patients IMHO. That went unnoticed for a short time, and then the Company was forced to address why patient screening stopped." --RK

You just don't know that. The 10-K sure sounds like regulators placed the hold:

In addition, our Phase III trial of DCVax-L is on a partial clinical hold for new screening for enrollment. We do not know what will happen with this partial hold. We may not be released from the screening hold and may not be able to complete the planned enrollment in this trial.

The wording there is very interesting. There is only one kind of "partial clinical hold" in the world, and it's the one regulators impose on an IND. And "be released" is a passive stance. It implies a third party that has power over the situation other than the one speaking and would do the "releasing."

If the sponsor was halting screening of their own accord, the trials registry need not have changed at all. They've slowed to a crawl or stopped enrolling completely despite having dozens of sites open in the past. Remember in that 10-k where they had 20 sites or something and just "6 patients enrolled?" The sponsor controls that flow. They can tell the sites to hold off for a time and they will. And they have to do this if they run out of cash (like they did when they were stuck at 22 patients in 2008). I think they were all told to stop screening and that the trial was put on partial clinical hold, as is their responsibility to disclose to all of the IRBs. The German trials entry apparently is the most thoroughly updated out of them all and this reflected that. Partial holds are material and are supposed to be PRed when they occur from a publicly traded company.

Manufacturing issue was never all that likely, imo. And now it's been 10 months and is almost impossible to be the cause. But definitely not because of some patent and change to TFF (not for DCVax-L yet!) or whatever else they plan to do AFTER approval. IMHO ;)

On another point, I always found this mention interesting in the 10-k, which I think first appeared in 2012:

There is also some possibility that changes requested by the FDA and/or other regulators could complicate the application process for product approval.

I've always been stumped by that, and they've never clarified. I know there is a mention that says EMA "informally" told NWBO they would not approve DCVax-L even if data were positive from this study unless they also performed additional early phase studies and a study in juveniles. Makes sense because really, this is the first study under IND 10206. The FIRST. Crazy...

Listen, when you WANT a certain outcome or want something to be true, there's a tendency to seek out and find "evidence" that suits only the outcome or "truth" you want. It's easy enough to do. But you have to shield your eyes and mind from anything that may dispel that "truth." Your post that I'm replying to is utter nonsense.

TGIF!

[Dan88]

In the scenario you speculated, nothing would prevent the company to say what has been or is going on. It is as simple as that.

Manufacturing issue at best may be just part of the long-unprecedented non-communicating quiet period from the company.

BTW, Linda must give up something to make the company into normalization so as to have a fair governance now, not later! It is not only for the public or other shareholders but for herself.

If she doesn't understand this, she will be the most unethic, stubborn and greedy ceo I have ever know or thought of!

For the sake of giving a chance for the success of DCVax so that it will contribute to cancer treatment for patients, Linda, you must act now.

I have kept buying as I have promoted:

Either $0.4 loss or $30/$300 gain. No change.

No reply doesn't mean I agree with your opinion. Simply no time.