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Caution is welcomed here. Unsubstantiated scare tactics are frowned upon….no wait….they are amusing.
NWBO -- the sponsor in this case (Think fire walled off Marnix Bosch) -- has limited but significant discretion to accept or stay a DMC recommended halt for efficacy. I'm not saying this is happening, I'm saying that there is a reason there are ethicists, independent statisticians, open review exchanges on limited matters, independent/firewalled committees, etc.
(I'm not talking about the individual clinicians, I'm talking about the trial sponsor)
"In almost all cases, a DMC is advisory to the sponsor; the sponsor decides whether to accept recommendations to discontinue a trial. FDA will rarely, if ever, tell a sponsor which decision to make. For trials that may be terminated early because a substantial benefit has been observed, however, consideration may still need to be given to the adequacy of data with regard to other issues such as safety, duration of benefit, outcomes in important subgroups and important secondary endpoints. We recommend that sponsors of trials that could potentially be terminated early for efficacy reasons discuss these issues with FDA prior to implementing the trial, when the statistical monitoring plan and early stopping boundaries are being developed. In these settings, consultation with FDA may provide the sponsor with important information regarding the regulatory and scientific implications of a decision and may lead to better decisions. Sponsors are encouraged to revisit these issues with FDA when considering DMC recommendations for early termination if new issues have arisen and/or if the regulatory implications of early termination were not adequately clarified at the outset of the trial."
Think this through just a little further. The events are not happening as quickly as even the company suspected. Thus safety can be evaluated to some degree without unblinding the data for a quick peak. Thus they can stick to the blinded trial, which means they will not compare treated to untreated patients except at predesignated interim looks.
The DMC can't say, "hey Joe, let's get 5 more events, unblind 'em, throw them in the statistical hopper with the others and see if separation is looking better or worse."
That is exactly what the entire field of statistical sequential analysis was meant to avoid because it creates the possibility for Type ! or Type 2 error. This is why the trial has predesignated DMC analysis points.
Statistical data for efficacy and futility are limited to preset "looks." This restriction on the DMC is done to prevent "Type I and type II error."
Sequential analysis is a major cornerstone in fields such as drug development, quality control in commercial production for things like airplanes, cars and ovens.
This is different from statistical data related to safety.
Thinking about sequential analysis again.
Warning: this is subtle.
This is the only "look" at data the DMC gets until the 2nd interim analysis. The 2nd analysis, as you know, will be triggered by 88 events. The DMC does not get an in-between extra peak. Thus, they are not waiting for a little more data to "see" if significance shows up. This would be strictly prohibited by sequential analysis.
That said, the sponsor could be waiting for a bit more data to accumulate that they will only "see" once the trial is unblinded. At 66 events, if they are confident there is statistical significance on their primary endpoint, and they also have statistical significance on their other endpoints, they may still want a little more "blinded" data to accumulate before the trial is officially unblinded. This would not be the DMC's idea, it would be the sponsor of the trial (those conducting the actual trial). They are certainly within their rights to think patients need this drug right now, and the trial should be halted for efficacy before the 2nd interim analysis, but they also may think once the data is unblinded, it might be very statistically sound to have accumulated somewhere around 70% - 75% blinded events in order to strengthen the powering for the FDA down the road.
This may seem counterintuitive, but I can see this playing out to protect current trial patients through early halt, in addition to protecting future patients by getting a tad more blinded data so that approval becomes a foregone conclusion.
Note: Futility does not become more probable as time goes on in between interim analysis, because the DMC does not get little "peaks" in between 66 and 88 events.
OK, that sounds more accurate, I knew I missed something. Thanks.
I do not write articles…but I personally use the market cap to compare with companies in the same area. I also keep track of the market cap right now because it recently surpassed the magic 300 million mark. I also think it helps to keep track of the warrants and options that are converting, because this likely reduces the immediate need for financing -- I think.
Fair Enough. I'll stay late after class too.
Let's take it back to the November prospectus and work forward.
After the November financing there were approx:
38.5 Million shares outstanding
25 million unexercised options and warrants.
But the January manufacturing Expansion added
5 million shares outstanding
for a total of 43.5 million outstanding.
It also added 2.43 million in unexercised warrants
for a total of 27.4 million in unexercised warrants and options.
---------
So, if Linda has been tracking options and warrants being exercised, and she gets 51million shares outstanding,
That means the amount of unexercised shares is 27. 4 million - 7. 5 = 20 million rounded off.
So maybe we are closer 71 (instead of 72) million once all warrants and options are eventually exercised -- but maybe I did too much rounding off in my head.
So Scottrade probably is the closest of the three stat. services on real outstanding shares, but it probably does not keep track of the warrants and options that are exercised on a day to day basis. So Linda is correct, but that is because she is up to date.
Does that sound correct?
I know….if they were students, they'd all be staying late after class.
Linda Powers stated on February 10, 2014, NWBO has about 51,000,000 shares outstanding. Listen to tape at 27 minutes 44 seconds.
I'll go with that.
I believe when I last looked, there are about 23 million in unexercised warrants and options. NWBO would ultimately have 72 million shares outstanding once they were all exercised. I think.
Long.
Not including unexercised warrants and options, I believe we are now at a 366 million market cap, does that sound right?
7.21 x 51 million = 367 million.
Definition of 'EDGX'
A high-volume trading platform owned by Direct Edge ECN LLC, the third largest market center worldwide. EDGX is a type of electronic communication network (ECN) that allows traders to trade with one another directly on an exchange instead of having to go through a middleman. NYSE Arca, Nasdaq, and BATS are examples of other high-volume ECNs. In 2009, EDGX traded more than 2 billion shares of U.S. cash equity per day.
Betweenthelines, you earned your namesake!
"Well, 4,000 ft2 at ASCO is the top of the roof!
Vivek Subbiah's statement confirms that NWBO submitted their Abstract through the standard ASCO procedure -- not the (TIP) 'Trial in Progress' Procedure. Had they gone the TIP route, Vivek would be restricted from sharing ongoing data at his ASCO presentation. MD Anderson knows the rules better than anyone else.
This is really good news. For those of you who were around last year, there was even a chance he was going to present data at a different conference last fall, but the slow start for first-in-human studies made this untenable. Consequently, I feel very confident he will share data at ASCO. The fact that it is now late February 2014 when he is making this statement carries a great deal more meaning.
Les Goldman reminds me of a nice Hawkeye (Alan Alda). I've seen this video numerous times, but its always worth another listen. Alan Alda could easily play Les Goldman if this 'hope' comes to fruition. Anyway, just the musings of an investor.
I also appreciate the way NWBO designed the trials. There is a cross-over arm and compassionate use is available for those who do not qualify for the trial.
ITMN went from 13.00 to 37.00 today on successful phase III trial for fibrotic lung treatment which doubles overall survival. The drug has been improved in Europe for a few years now, so the results are not that surprising, but the price spike is. Many people will live longer and healthier lives due to this drug.
NWBO: Unexecised warrants, options plus outstanding shares = 72 million
POTENTIAL APPLICATION: APPROXIMATELY 15 MILLION PATIENTS IN U.S.
ITMN: " " = 82 million
POTENTIAL APPLICATION: 135,00 TO 500,000 PATIENTS IN U.S.
Adam Feuerenstein.
I forgot to mention, Argos AGS-003 appears to be further early confirmation that dendritic cell immunotherapy works -- much to the chagrin of AF.
(Continued from post 4883)
There was a public breakout session in at least one of the recent conferences Larry Smith traveled to. I assume a little more color is often given during those sessions. Questions/Answers. Why go to San Francisco or New York if one can sit on their derrier and stream?
I speculate "interesting" "anecdotal" "information" might be something akin to Linda stating: from what we are seeing, "we are encouraged," as she stated about Direct in her most recent webcast that the whole world had access to.
I found the ARGOS prospectus for their IPO from February 12, 2014.
http://www.sec.gov/Archives/edgar/data/1105533/000119312514040941/d621316d424b4.htm
Initial thoughts:
1. They are behind DCVAX phase 3 trial by about a year.
2. AGS-003 treats Kidney Cancer, but both AGS-003 and DC-VAX appear to be capable of treating most or all solid tumor cancers.
3. They do not have the equivalent of DCVAX-Direct, so they may start a phase 2 trial for AGS-003 on various solid tumor cancers. Their lack of DCVAX-Direct like platform could create problems. There is nothing yet on clinical trials.gov related to a multiple tumor trial for AGS-003.
4. They do not seem to be close to the manufacturing advancements and certifications throughout the world that NWBO has.
5. One good similarity is that ARGOS is seeing that same 80% response rate from dendritic therapy.
6. Despite the NIH grant, it appears they do not have orphan status yet, which would otherwise extend their older patents. However, like IMUC, they could probably get orphan status.
Larry Smith,"Smith on Stocks," answers a couple questions on NWBO in his February 25, 2014 "Mailbox."
I think this section is open to non-subscribers. http://smithonstocks.com/comp/
Let's play a game. Find the word below in his "Mailbox" column.
Anecdotal
Well, the DMC decision was not announced this morning. FatCat is next up in the office pool for tomorrow morning.
In other words….
63 ft x 63 ft = 4000 Sq Ft.
Basically, that is bigger than a 1 story, 5 bedroom, 3 full bath home (Except in Texas). In other states, its an inner city residential lot. What's up with that?
I never win at office pools. Maybe this time I….no……who guessed Wednesday? Oh well, the DMC is an unpredictable acronym.
Ba dum tshhh:)
Red.
In the event we have a DMC continuance decision, your concern that there may be a sell-off of weak hands is certainly reasonable. However, I think institutions understand sequential analysis. The statistical hurdle gets lower each go around (aka: interim analysis) with the O'brien-Fleming method. Therefore, while uneducated hands might abandon ship, the big dogs will likely accumulate shortly thereafter as we await the 88th event.
So I hope for efficacy but plan for continuance. IMHO
German Clinics.
IMHO
1. If DCVAX-l does receive a DMC Halt for efficacy, what will transpire in all those German clinics?
I think the 21(?) German clinics prepared to open for the DCVAX-L trial would have almost instantaneous capacity to convert to compassionate use centers, and being that German approval for compassionate use reimbursement for the first year is nearly or equally equivalent to market approval, this could be very helpful revenue to complete EMA and FDA approval in addition to partially financing the ongoing DCVAX direct trial.
2. If the DMC instead rules on a continuance, the German clinics will surely open to increase enrollment and move NWBO toward full enrollment much more quickly. In the meantime, the eventual compassionate use reimbursement from the German Government will still help finance the DCVAX trials.
I'm not savvy on technicals, but….
I think we are near a top line 52 week resistance.
Agreed.
I think it has several benefits.
1. Awareness
2. Letting ASCO know they are very invested in this year's conference.
3. Handling a flood of people.
4. Ease for media interaction.
5. Contacts/Partnering.
6. Demonstrating Confidence.
Amazing!
Thanks for relating these examples to the board.
I am sorry for your loss. You truly represent what it means to be a long investor. Thank You for sharing your thoughts.
My comment was not directed at anyone in particular. I've just noticed we are all a little ornery right now.
I'm starting to think the ASCO submission went through the normal abstract process. I think Trials in Progress ("TIP") are reserved for blinded trials. Earlier, I was mostly going on the premise that NWBO filed under the "trial in progress" procedure:
"Trials submitted to this session are ongoing and have not reached prespecified endpoints for analysis. As such, inclusion of results would be improper and is strictly forbidden."
I never really give advice, but this board has been a nice oasis, so I thought I'd offer my 2 cents….
Dubious or hopeful, sometimes eliminating excess drama can lead to more constructive conversations. I still give into the soap-opera conversations as well, but upon reflection, I internally thank the person who intentionally or unintentionally pushed my buttons, because it taught me more about myself. Hopefully by the time I meet my maker, I'll not have so many buttons.
Excluding the current phase three trial, clinical and compassionate use over the past ten years = over 200 patients amounting to 1000 treatments. The Response Rate was consistently approximately 80% of the total pool. Only one possibly related serious adverse event. The compassionate use program covers a broad range of cancers including but not limited to GBM* cancer.
From January 2014 webcast.
* We know from other sources that GBM is one of the types of cancers treated through NWBO's compassionate use program.
Merci, toi aussi!
Its been a long week. I do not blame Linda at all for giving us her best guess regarding the timing of a DMC decision. If everyone else is like me, they've been watching for the pot to boil. Have a great weekend.
P.S. I'm not speaking on behalf of anyone else.
Agreed.
Thanks John and "BBking". Wouldn't you know it. That was the only post I skipped over today. Great to hear.
Let me be clear, I am not an insider. I get my knowledge from DD. I even gave you the minute on the public webcast to hear info. The Red Cross info was a news release a year or two ago. The "glimpse" language was from a public webcast….etc. I'm starting to agree with Bio, this is becoming a "brain drain." Anyway, have a good weekend.
The institutions and Governments I listed are the high level associations NWBO has.
The enrollment data on DCVAX-L is not specific at this time. If there is a continuance by the DMC, this will be an opportunity for NWBO to update us on enrollment numbers, because this is info the DMC is allowed to share at interim updates (under their Guidelines). See previous PRANA interim updates on imagine and reach trials for examples.
Results are certainly under wraps on DCVAX-L, phase III, because this is a blinded trial.
Results on Direct are "encouraging" but only a few have gone through early dosing. We will be updated with "glimpses" in the spring and summer.
Sarah Cannon has letter of intent to collaborate in clinical trials on upcoming Europe DCVAX-Direct.
I already gave you the response rate shared by LP in her January webcast, partially related to the Israel compassionate use program.
Note: Other associations with NWBO include:
10. UCLA.
11. University Hospital in Cologne.