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"-They have added participating sites in Canada, UK, and Germany...and from the 10K the reasons for adding sites when the trial is almost enrolled is essentially to facilitate immediate market penetration in those countries...they have orphan drug designation and HE and PIM approval."
Canada is physically associated with the US, but in more ways, associated with Europe, specifically the UK and France, as you know.
The activity in Canada is great... but I don't know whether Canadian marketing approval hinges on FDA approval, or not.
Also not sure if the EMA and the FDA can end up with different decisions, given that it is a joint trial. This is a fundamental question. My excuse for not knowing... I guess I missed about 100K posts over the last year?
I do remember that the EMA usually takes longer than the FDA... which implies different decisions, but again, my understanding is that this is a joint trial, so not sure if that changes the rules.
I get it. Your an M.D.. That makes you (the Real Mc) Coy. He's right.
I think Flipper was just trying to clarify earlier, as he has done now with his underlines, that he was only talking about Les (and others) not having info about the actual trial results data.
He was clarifying something he said that I referenced, and may have referenced out of context.
Hope that clears that all up. smileface
Happy New Year to new and old Friends... including the mad chess player and his checkered mate.
Northwest knows a little more than we know. Even just knowing when patients got treated and how many continue to get treatment is more info than we have. People here have done models that lack that specific information, yet they still have some confidence in those models.
If Northwest's screening requirements were unique, than maybe they don't have great historical norms to compare too, but they could certainly attempt to model the difference.
They do know more than us. It is unavoidable.
Not saying they know the chances of success are great, just saying they know more than we do.
"I have been thinking along that same line and it would also agree with what Les said about them only getting the 12M toxic financing because the news would get the price up so they could get better terms. So..."
That does make sense, but I thought Les was probably talking about something to do with Direct.
Flipper said today that he didn't think Les would be in on any such details about DCVax-L, and that sounded right to me. On the other hand, if the proposed model of what is going on is accurate, how would you hide something of that scale. $ scale. Or for that matter, how would they explain to Les what was going on with the patents.
Thanks. I realize this has all been said by a lot of different people at different times; I am just adding the personality issue.
Northwest posturing for a default is not a bad sign. It makes total sense given LP's demonstrated style, if you believe they are currently in a look at efficacy.
First of all, the randomization and enrollment numbers line up perfectly for a look at efficacy in my opinion. If the data shows at least 6 months PFS likely, then they might get marketing approval with a confirmatory that requires no more patients to be randomized. If efficacy shows at least 4 months pfs likely, then they might get marketing approval with a confirmatory that requires no more patients to be screened.
If they are currently looking at efficacy, then LP's proven character would require preparation for all possible outcomes. She is a control freak. That is absolutely undeniable. As a control freak, anything she cannot control must be dealt with in some other way. The most likely result of an efficacy look is continue, but she appears to have prepared for the less likely marketing approval, and the still less likely halt for futility.
She has apparently prepared for the possibility of an early marketing approval by dumping huge $ into getting production capacity up to the levels that would be required, probably with all the automation they can come up with in the time alloted. And she has apparently prepared for the tiny chance of futility by putting some (key?) patents out of the reach of creditors.
If the above is true it doesn't mean anything nefarious is going on, nor does it mean a default is likely. But it does explain the bazaar things going on lately, in my opinion.
The only disturbing issue would be the apparent plan to default if DCVax-L gets called for futility. One might think they could survive that and limp along till Direct matures. But that is not the apparent plan in my opinion.
It would be in LP's demonstrated character to prepare for a finding of futility even if she thought the odds of such were very tiny.
Method B, though, remains un-identified, or did that change recently?
Makes good sense for selection. Do you recall any talk at all about tweeking to try to effect the cytokines or CD8 and CD4 balance?
"Hey check out the cap now under 300m. :). LMAO"
I am not purely a cheerleader here any longer. In part, I must admit, because my bank roll is 2000 leagues under the sea at another smallcap, and I am waiting for some miracle to pump it full of air. But I am also truely concerned about the apparent situation with NWBO. The enormous expeditures, and the posturing as if in preparation for a default. So I agree with what many of the bears are saying to the extent that it warns the longs not to bet the farm.
I expect to invest about half my roll here down the road. I don't have a family. I can do that.
But when I hear about AF and DrJrkl's "Investment "Thesis"", it makes my stomache turn a little bit, and my heart pound a little bit.
To me, that investment thesis is transparently a tool for manipulation of smallcap biotech funding. To the extent that they can get people to buy into the idea, they don't have to bash every new biotech contiously, they only have to hammer them down below a cap of $300M, then the unnatural forces they have conjured help drag the company down, and they can move on to the next potential competitor or possible future acquisition.
What flipper said made sense to me. Where they left of with the Direct trial was that they were able to predict the outcome fairly well for a given patient based on those markers.
So, are those markers under their control, or are they just a reflection of the patient's immune system health? In the next phase for Direct they will be trying to tweak the process to more repeatedly get the marker mix that they saw as successfull. Maybe they already know from tweaking in Phase 1 what worked in that regard, and what didn't work. If not, there will be more tweaking in phase 2. But they will see the results quickly, in terms of those markers. No gauruntee that accomplishing the successfull marker proportions from phase 1 will result in greater efficacy in phase 2, due to a question about cause and effect... but extremely likely that if they can tweak the process to get the marker balance they want then they will improve efficacy.
Once they have accomplished that they can start arms along those lines... and only then, likely, start adding a touch of blockade inhibitor, which is a tad dangerous, but may prove well worth the added risk, particularly when it might be needed in such low doses once they have the cytokine response they are looking for. That will be done in different trial arms from the optimized straight Direct arms.
Does that sound right Flipper?
I don't know Jack.
The biggest concern would be if L fails. Then as you describe, after bankrupty of NWBO, if they managed to transfer all patents to Cognate, then wouldn't that be the same thing as taking Direct Private?
Maybe they can't transfer all the patents to Cognate. I think some people have made strong arguments that is not possible. But because they are positioned to transfer many of the patents to whoever they want... I worry about it.
As far as the warnings in the 10K or 10Q about possible bankruptcy, I see those often for small-cap biotechs. Isn't that a standard caution?
Sorry sturmndrang555. I wasn't responding to you directly. I wasn't rebutting anyone on anything. Just trying to tie into the closest related thread.
I think most die-hard longs are in deeply. Hopefully not the farm, but deep enough that they cannot lift the SP at this point.
I think there is a chance of failure, but as you say, that is par of the course. I think the low cap really is due to very large $ not wanting the company to succeed. I used to think that was BP and or Hedge Funds, but after reading the recent write-up on trial costs that RK posted, I wonder if it is the insurance companies that were behind Phase V and other such efforts.
A big fish wandered onto the board a year or so ago and said that the lack of interest from many institutions was the unusual relationship between LP-NWBO and ... LP-Cognate. He did not say that the concern was the chance of failure.
That relationship with Cognate should worry people. Posters have said they see the recent arrangement as posturing against a takeover. It might be, but how do they know that LP is not just planning on taking Direct private? I think their biggest consolation is that Woodford is powerful enough to prevent it, if it would be illegal. And my guess is that it would be illegal. My residual concern is that she could work out a deal with Woodford, or all the institutional investors and leave retail holding the bag. Companies do it all the time. People are trusting that she would not do it to them.
I will not be surprised if LP turns out to be as trustworthy as most of the longs give her credit for... but if retail gets burned, it will be at least the third time in the last year for the small number of small-cap biotechs that I watch.
Maybe that $180M was already contracted for design + tooling/infastructure etc for the ramp-up in mfg. And of course a small part of that would go to regular old production of the vaccine.
I agree that $180M is an absolutely enormous amount of money and should concern anyone invested. I agree that it is almost an order of magnitude larger than what could have been spent on making the vaccine for the trials, so anybody who thought that is where it was going was out on a very thin limb.
But I have decided to rationalize the enormous expenditures as part of the enormous cost for a production ramp-up. Ie for further automation as well as expansion.
I don't know that such could cost $180M (or most of that), I just know that the costs for that kind of design work and subsequent tooling and V&V are uuuuuuuuuuuge! So it is conceivable from my perspective.
Maybe they hadn't found one yet.
Northwest is looking for a blockade inhibitor / checkpoint modulator for at least one leg of the Direct Phase 2 trial. That is what LP has said in recent webcasts. Why could the recent $12M expenditure not have been to purchase such?
Some companies setup partnerships to utilize BIs sold by other companies as adjuncts to their products... but that is not LP's style. If she can buy one, she will, and there are a large number in constant development by many different companies at this point.
Maybe they bought a Blockade Inhibitor with the $12M.
Fair enough. But I didn't say I thought the halt was for futility. I didn't say that regulatory asked for it. I said I thought it was for an interim look. Any such look could result in continue, AA, or a finding of utility. NWBO was apparently worried enough about the results to lower the bar, so I think you have to consider a decision of futility at least a remote possibility.
Though I really don't know much about these things, as advertised, as far as I know, a halt for futility can simply be a recommendation from the DMC that the odds of success are low enough that spending more money doesn't make sense. It does not have to come from an agency.
I retract my moment of clarity. Having rationalized recent enormous expenditures as preparation for large scale production, I can't see LP throwing in the towel in the very near term. I still think they are awaiting the results of an interim look, hoping for AA and or German reimbursement, and possibly fearful of the small chance of something far less pleasing. But the primary focus likely remains on completing the full trial. I don't remember when that is projected to happen, but if it is feasible by June 1, or before, then of course that is usually the focus.
There is no connection. That is what makes it so strange.
That's wierd. A golden cross.
I'm not supersticous, but I did the star charts for TPIV anyway as kind of a joke. I couldn't believe what I saw. So, I double checked with tea leaves... and there it was again. Being the doubter that I am, I triple checked with the Tarot cards... and they are all saying the same thing. They are all saying that the $TPIV SP is going to triple in the near future. I couldn't nail down the day, but it was sometime in the next few trading days.
I still thought I should just ignore all that hocus-pocus BS... but now you and your bald cat say that there is a golden cross leading forth. I don't know man. I think the stars have indeed aligned.
I wonder how people are viewing / modeling GBM recurrence after DCVax-L treatment? When you (-all) talk about a subsequent mutation allowing the cancer to recurr, what are you visualizing?
Are you thinking that a previous antigen target is now gone due to the mutation, and the loss of that target has moved the immune system balance in favor of the cancer, or that a resulting cancer functional change has occurred due to the mutation that puts the balance in favor of the tumor / cancer. Ie the addition of cloaking. Ie via hyaluronic slime... just examples.
The model that DCVax-L is attacking many antigens leans in favor of the second view, in my opinion.
While attacking many antigens may prove to be better than attacking a single antigen in greater force as AF claims, nobody is claiming that a cancer vaccine has to attack all antigens. Therefore it should be a little surprising that a mutation could be responsible for a cancer recurring, unless that mutation is substantially advantageous to the cancer, and thus upsets the balance.
Look forward to your views, (except from the two posters that always respond in an aggressive way to the first line without reading the rest of the post, thus making no sense).
Very useful post CherryTree. Educational. Thank You.
-------------------- Post with this info, etc -------------------
I am not sure why you are having so much difficulty understanding this. It is basic math, but OK let me try again per your request.
Here is the shares of common stock right of the IHub board site:
Common Shares Outstanding: 92,358,027 (as of 11-6-15)
Options Outstanding: 1,551,000 (as of 5-15: needs updating)
Convertible Notes: 2,343,000 (as of 5-15: needs updating
Share purchase warrants: 28,330,000 (as of 5-15: needs updating)
Total Fully Diluted Shares: 124,582,027 (needs updating)
Beneficial Ownership of NWBO Common Stock held by:
0.44% Security Holders - Employees/Directors 409,467
1.7% Security Holder - Linda Powers 1,572,500
.9% Security Holder - Toucan Capital Fund 804,145
2% Security Holder- Toucan Partners, LLC 2,211,784
29% Security Holder – Cognate BioServices (11-15): 27,194,366
28% Security Holder - Woodford Investment Management 25,915,937
4.5% Security Holder – Dennis Mehiel: 4,125,949
(under 5%, not listed on 11-6-15 Proxy)
Total (11-6-2015): 58,107,899
Woodford holding divided in Common Stock outstanding = 26,915,937 = 29.14%
----------
92,358,027
I agree that it seems improper that we have to guess what the money is being spent on. If it is the actual production cost, for example, then NWBO is in trouble, even if automation later cuts production costs in half.
But if the vast majority of the money is going to tooling for more automated production, then that might not be something the company would want to talk about. Investors might question the decision to spend at that level without knowing for certain whether the new production capabilities will ever be utilized. And LP might prefer to not have the debate.
And or... if I were to venture onto the thin ice of the hopefull and happy daze of yestermonth, I could quote Etienne555 quoting Sun Tzu from "The Art of War", saying,
“Let your plans be dark and impenetrable as night, and when you move, fall like a thunderbolt.”.
Yes. I forgot about the issue of crossing over. I now recall the debate. Certainly would make it messy analysis.
I don't understand why some believe that a failing PFS (if it were to happen) would not be spared by a good OS. OS would take longer, but... unless PFS was worse, does it seem reasonable that sufficient OS improvement, even as a secondary objective would not win approval?
I know there are statistical issues with changing trial requirements to fit results, that would not be transparent to a layman. However, there is also the real concern that regulators can become irrational, power drunk "Nurse Ratchet" / "you didn't say mother may I?" in arbitration. I don't see why denial based on OS would not be the latter in this case.
Sounds reasonable. They could use the down time and excess $ to
1) Build what new automated production tooling they have designed to date.
2) Install that new tooling.
3) Train the idle techs to use the new tooling (as you said).
4) Perform regulatory Validation and Verification (V&V) on the new tooling.
All that would be an accelerated effort, and would be very expensive.
But there would still be a longer, ongoing effort to design the next or final generation production tooling. That might pause to focus on this immediate effort that you suggest, but it would resume thereafter and would benefit from what they learn in this immediate effort.
As I pointed out a couple of posts ago, automation of DCVax-L production is ongoing, and will be ongoing for some time. That is a certainty.
Tooling charges can be incredibly high. That is a certainty.
iwasadiver has suggested that such charges might account for the spending to Cognate that appears far beyond what production costs should be. I agreed that it is possible. Hard to be sure, but it is a reasonable explanation.
(Not sure why we should be in a position to have to guess such things... but given that we are, it seems a good guess.)
All that communication happened in the last hour. Guess you had to be there.
Lets see... your short... so, that would make it about 6 months. Come back in 5 months.
We don't know what they are spending the money on, we just know the burn rate.
The point I was making about the money being late is that you shouldn't use the funding date (Oct 30) as the start date. You should use the date they were scheduled to run out of money the prior time. The date the needed more money, not the date that they got more money.
If Northwest pays for the tooling design, which is probably a larger cost than making the tooling, then they should own it, and have the right to move it to another contract manufacturer, for instance. And Cognate should not have the right to replicate it for another customer.
Not sure if that notion conflicts with what you are saying.
Why do you say that they had to have money left? They were totally stretched when they got that last money from Woodford. It was late. They were due for this last round given the posted burn rate. It was that simple.
"Buy low, sell high" has a corollary. "Buy when the shorts are high..."
At this point I suppose there only needs to be a plausible explanation to be ok with expenditures long enough to hear something positive or semi-positive back from the Woodford camp. As long as your not super-overweight.
Myself I am a gambler and take huge risks, so seeing the $ anomalies makes me worry for anyone doing the same here. The immunotherapies, and this stock in particular, draw in a lot of very good personalities that do tend to lead more with their hearts in spite of being very intelligent. Those aren't the kind of people that you want to see crying down the road. So anything that looks out of sorts begs caution against being overweight.
That said, I would agree that tooling is unbelievably expensive, and most of that expense goes to design. And I would agree that it would be reasonable for Northwest to pay for that tooling, both the design and the build, as long as they own it afterwards.
In mechanical, when people first learn what it costs to have a mold designed and produced they are usually shocked. In Electronics, the design of a test fixture for a circuit can cost substantially more, and take substantially longer than the design of the product itself. I know that for certain because I recently designed a test fixture for a product that I had designed.
Somebody could argue that Cognate was already in production before Woodford... but that is misleading. LP stated months ago that they were still 2 years from having full automation for DCVax-L. That means that a great deal of development is ongoing, and could be at peak levels at this moment. So... I would agree that everything lines up with your assertion / your proposed explanation for the recent high expenditures to Cognate.
I just don't know what magnitude of $ is plausible, but again... tooling is famously more expensive than people can imagine.
So this scientific american article is where you got the previous $312M from. I think you left out the link earlier today.
$2.5B !!!!! That's twice what it was yesterday! No wonder LP couldn't give a good estimate years ago, it's a fast moving target!
I will look at the article.
I was trying to stay as far from the detail as I could.
IMUC has put X patients through trials (all phase 1, 2 trials for all drugs). They have spent Y dollars in their lifetime. One would expect that trial costs would account for Z percent of total $ spent by the company from birth. So their trial costs per patient are (very) roughly ZY/X.
If your correction of roughly double the end-trial patients being cared for is right, then the estimate becomes ZY/2X.
I certainly agree that Northwest's trial costs are off the map. Something is wrong. However, I do not agree that their DCVax-L process should be relatively cheap. I don't think that is true, and many critics in the past specifically pointed to the high cost of dealing with both DC's and tumor samples.
In the end, I think the debate about cost will likely come down to exactly the issues you are debating with RK. What of Cognate's expenses should be passed on to Northwest.
I wouldn't agree that Northwest should not have to pay any of the mfg development costs. As far as I know, out here in Silicon Valley, the parent company does pay for test fixture development, and for the build of the test fixture, but in the end they own the test fixture and all associated patents. The parent company might design the test fixture themselves, or may contract the design out to the contract manufacturer. Usually more of the former, but something in between. But in all cases, the parent company would own the test fixture, and again, all associated process patents, as far as I know.
That may be where much debate lies in the future. That, and similar questions about land and buildings. If Northwest paid for it, but it is now in Cognates name, then something is wrong. I think that one has been pointed out.
I don't like moving down these paths while a bunch of people are under water. This is not a good time to say negative things. If you started saying these things long ago, while the SP was higher, which is likely, then you are in a different situation. So... I have to look for a silver lining and then back off I suppose. I wanted to go on random-walkabout through all these issues as I returned to focus on NWBO... but it is not a good time to do that. I add to much noise. Probably less significance than I realize... but still probably not a good time to randomly bounce around, loudly.
The silver lining is... months ago when Woodford came aboard people got very excited and the SP rose. It rose because his involvement meant the company had likely been thoroughly veted by a major leaguer... and because his large presence provided security in other ways. Well, one out of two isn't bad. He is seeing that these issues get resolved. He doesn't have preferred or otherwise special stock as far as I know. And he is not private owner of half of Cognate, as far as I know. So... he is going to set things right for people like him which includes regular old retail shareholders... probably. So... everything will be ok, probably.