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Expert Financial Analysis and Reporting

Northwest Biotherapeutics: Thoughts on Suspension of Screening of New Patients in the Phase 3 DCVax-L Trial

Reason for Report

On August 21, Northwest put out a press release that said that screening of new patients has been temporarily suspended while the Company submits certain information (unspecified) to regulators. Patients enrolled in the trial continue to receive drug treatment in accordance with the protocol which involves multiple injections over time. Screening involves the initial evaluation of patients to determine if they meet eligibility requirements for the trial. All enrolled patients in the trial continue to receive DCVax-L in accordance with the trial protocol. There were some reports in blogs that said the trial had been halted which might have meant that treatment would be halted for patients already enrolled; these were incorrect.

The Company also said that the phase 3 trial of DCVax-L is ongoing and that 300 of the 348 patients anticipated are now enrolled in the trial. The primary endpoint of the trial is the occurrence of 248 cases of progression in the combined drug and control group. Secondary endpoints include overall survival and other measures. When the primary endpoint is reached, the data will be collected and analyzed to determine if the trial is successful. This is the first enrollment update that we have had in quite some time. There has been some concern that the trial was having trouble enrolling patients but this is not the case as it is now 86% enrolled. Also the pace of enrollment speeds up as a trial progresses and centers become experienced in screening and enrolling patients so that completing this trial should be expeditious if the suspension on screening is lifted.

Conclusion or Lack Thereof

In this report, I go through possible scenarios that could have led to this suspension of screening, but none of them are sufficiently convincing so as to allow me to draw a firm conclusion. My basic feeling is that something unusual is occurring and that with the facts that we have available, I cannot offer a reasonable analysis of what that is. Northwest has said that “The Company is in the process of preparing the trial information for regulatory review and anticipates submission within the next couple of weeks.” The Company did not specify the type of information being submitted to the regulators might be. I hope that in a “couple of weeks” we will have more information that will allow us to better understand what is going on.

Based on available information, I can come up with the very favorable hypothesis that the trial has met its end point or the more dire hypotheses that: (1) there is a safety issue or (2) the results on an interim basis suggest that the trial is unlikely to successfully meet its endpoint. However, I have a feeling (purely intuitive) that there is something else going on that enhances or goes beyond these possible scenarios.

It seems to me that the request for more data by the regulators indicates that regulators believe that the resultant data could answer whatever questions have arisen and allow the trial to continue. If there were an unresolvable issue, they would (seemingly) have halted dosing in patients enrolled in the trial. This suggests that in coming weeks, the suspension on screening of new patients could be lifted and the enrollment in the trial completed.

There is another concern about the financial position of Northwest as the Company obviously needs to bring in more capital. However, the heavy involvement and deep pockets of Neil Woodford strongly suggests that if the trial continues that he and other investors who follow his lead will provide the needed capital. I estimate that Mr. Woodford has over $120 million invested in the company and is not going to stand quietly aside if the Company needs more money. Based on the experience of two past financings for Northwest, this financing would be done at a premium and without warrants.

My Thoughts on This Suspension of Screening for Enrollment

I have tried to think through the possible reasons for the suspension of enrollment, but none of them explain to me what is going on. The involvement of the regulators in this way at this stage of the trial is unusual. Before starting a phase 3 trial, companies confer with the FDA and other regulators to get a sense of what the FDA or other regulators might require in terms of conduct and data from the clinical trial in order to approve a drug. This is guidance as the FDA does not officially approve a trial design except in the case of a Special Protocol Assessment, which is not applicable in this DCVax-L phase 3 trial.

After a company begins a phase 3 trial a panel of outside experts called the Data Safety and Monitoring Board (DSMB) monitors the results of the trial. The primary goal of the DSMB is to monitor safety issues in the trial. It looks for side effects that are possibly attributable to the drug or perhaps unexpectedly high (or low) morbidity and mortality. FDA guidance documents state that the DSMB functions as an advisor to the trial sponsor.

The regulators and the Company are blinded to the results of the trial. In general, the DSMB does not look at the results of every single patient as they come in. It sees the aggregated results for all patients treated, both those on drug and on control. Again, it is looking for signals of potentially dangerous side effects or changes in expected disease progression or mortality. However, at pre-specified points in the trial, the DSMB does take interim looks at efficacy as well as safety.

Throughout the trial process, a regulator only becomes involved if necessary. Let me go through possible scenarios in which a regulator would become involved starting with safety. If there is any serious safety issue, the regulator is immediately alerted and if the danger is great enough the trial is halted and drug treatment probably would be halted for all patients. In considering whether this is a safety issue, I considered the following points:

  • Based on the phase 1 results, Northwest designed and began a phase 2 study in 2007 that was a 140 patient open label randomized trial which was stopped due to trial design issues. The Company then began a 240 patient randomized controlled trial. Financial issues associated with the market crash of 2008 forced the Company to halt new enrollment. After regaining its financial footing (the Company could have gone bankrupt without the financial support of Linda Powers), in 2011, Northwest resumed enrollment in the trial.  In the spring of 2012, the trial became a phase 3 trial. In 2014, in accordance with a pre-specified statistical analysis plan the study was expanded to 348 patients. I would think that if there were a side effect that surfaced shortly after treatment began or much farther in the course of treatment that this might have been detected much earlier than 2015.
  • If there was a serious side effect issue, why would the regulators allow patients already receiving the drug to continue with treatment?
  • All of the available clinical data on DCVax-L suggests a side effect profile in which side effects are a result of the injection and boosting of the immune system. This includes injection site reaction, fever and chills-none of which have been a problem and last only for a day or two. Indeed, one of the compelling features of DCVax-L has been the absence of severe side effects seen with chemotherapy.
  • There have been a large number of cancer vaccine trials using diverse technologies and safety has never been a serious concern. The general thinking is that cancer vaccines as a class do not have serious side effect concerns.
  • DCVax-L is a dendritic cell cancer vaccine and we have clinical data from two other such vaccines. Dendron’s Provenge was approved and its side effect profile was comparable to what has been reported with DCVax-L-injection site reactions, fever and chills when first given. Similarly, ImmunoCellular’s ICT-107 reported the same type of side effects as Provenge in its phase 2 trial. This suggests that there is no class effect that produces serious side effects.

One cannot rule out anything at this point, but these points argue strongly against there being a safety issue.

If it is not a safety issue, then it could have something to do with efficacy and I would remind you that the DSMB generally (always) does an efficacy evaluation only at pre-specified interim points in the trial. There has been no announcement of an interim review, but this is not always disclosed by a company. We can’t rule out that an interim review has been conducted. The DSMB after an interim review can then make one of three recommendations to the Company:

  • there are no safety concerns and the trial should continue,
  • the trial has met its primary endpoint, could be ended and the NDA  filed, or
  • the trial is unlikely to meet its primary endpoint and it is futile to continue.

If the trial has met its endpoint, the Company would likely meet with the regulators with two important points to consider. It might be unethical to withhold the drug from the control group so that patients in the control group should immediately be switched to the drug. This would explain the decision of the regulators to halt screening and enrolling any more patients in the control arm of the study. They would also want to carefully go over the data set to make sure that the decision to end the trial at this time is the right one. Ending a trial early can seriously impact gathering data that may be critical to understanding of the drug in actual clinical practice. There is only one chance to do a controlled trial with a drug to define how it differs from standard of care and ending a trial early has consequences. In this trial, patients in the control group who progress are switched to DCVax-L which lessens the ethical issue. I think that Northwest might elect to continue the trial for the reasons I just stated.

In the futility scenario, the Company can elect to continue the trial after conferring with the regulators. If there is no important safety issue, there is little risk to patients if the trial continues. It has now been reasonably established that immunotherapy produces a prolonged duration of effect in a subset of patients. It is possible that this could lead to final results coming in positive even in the event of disappointing interim results. The results seen in the phase 1/2 trial of DCVax-L and in the information arm of the phase 3 trial would argue strongly against the futility scenario.

In all three of these scenarios, I am uncertain as to why the regulators are requesting information while the trial is ongoing. My basic conclusion is that with the facts which we have available, I cannot confidently offer an analysis of what is going on. Northwest has said that “The Company is in the process of preparing the trial information for regulatory review and anticipates submission within the next couple of weeks.” I hope that at that point in time we will be able to understand what is going on.

Tagged as , , + Categorized as Company Reports


  1. Larry, I think that there is an assumption (which you also seem to be making) that the regulators are looking at data regarding the screening of patients. I believe the company has only said that there is a halt on screening of new patients while they submit data from the trial to the regulators. So, I don’t see where it definitively says they are submitting “information on screening of patients”. Maybe I missed that somewhere?

  2. Hi Larry and welcome back…..Hope you had a great vacation….Thank you so much for putting together this piece on NWBO and its fiasco of news day back on Friday the 17th…..Of course, you have zeroed in on the correct question that has no obvious answer and that is the reason for the sell-off in the stock….My humble opinion is that the leadership of this company is not shareholder friendly nor wise in the world of presenting clear and timely information….Hence, we have more law suits than we have patients enrolling in our trials….I really appreciate your efforts here and in the past to try and de-code what is actually going on….I want to write a letter to the BOD of NWBO….Do you think that is the way to go??? I have never written a letter to any company….I don’t know how to get them to respond to the many issues that they say they are involved in, yet never follow-up after the tease….ie: pricing of German treatments, private pay patients in Germany, part 2 of the UK submission, hospitals and treatments for phase II “D”, collaborations, and lastly, will they tell us when this material is submitted and the nature of it??? Hence, my desire to write to the BOD as calls and requests to Les have gone completely un-answered….I am frustrated and confused by this leadership, as you can read in my comments here….I hope you publish this blog on SA and get some other knowledgeable people to add their comments and opinions….I certainly am glad I subscribe to your reports and will continue to do so…In closing, I will publicly state I still have 100% confidence in their science and 20% in their press dept. cheers, longNWBO

  3. I’m not certain regulators requested information on screening. Instead, the company stated on Aug. 21 that they would provide trial information to regulators. They stated they were in the midst of a continuing dialogue with regulators. While breakthrough status was not given, the literature states rolling reviews can occur without that status. Also, EAMS would require phase III data review. If you think the trial might need to continue, and the situation (providing information to regulators) is outside the three primary possibilities, I’d suggest the review was either for EAMS review and/or HE/NICE price negotiations.

  4. Sooooooooo many possibilities……wish someone could find out what is going on……I am certain the company will NOT tell us cheers longNWBO

  5. I think what influences me in the net-zero conclusion of all the hints out there is that Linda said in a Reuters interview on 8/21 that the blog forces were trying to make good news into bad news. To me this casual slip of hers could mean that this is more about compelling interim data than it is about poor enrollment or screening. I can imagine the FDA would otherwise want to look into why enrollment still has not been completed by now, but then why stop the screening process for that kind of investigation.

  6. We are trying to put together a puzzle in which some of the pieces are missing.

  7. Something unusual is indeed happening. Who were the regulators that temporarily halted the trial? What was their motivation for doing so? Were outside organizations petitioning the regulators to halt the trials? Why hasn’t the company issued a press release that addresses at least some of these questions?

  8. NWBO temporarily suspended the screenings, (not the regulators).

  9. NWBO suspended screening of new patients, did NOT suspend the trial. Enrolled patients are continuing to receive therapy injections and follow-up as per the trial. One other possibility that occurs is that the screening was temporarily halted due to imminent approval of and contracting for reimbursement of treatment costs for new patients.

    If so, it is possible NWBO plans to put new patients into treatment for reimbursement rather than the no cost trial for the patient (and the chance of treatment by placebo rather than therapy).

    It is also possible the European agencies may want to look at the screening criteria in use to also impose similar eligibility criteria for reimbursement of costs to the patient. This would be designed to enhance the chance of successful treatment outcome and further justify agency reimbursement costs by making it more likely that survival and quality of life are improved by providing treatment reimbursement to those most likely to improve……a form of rationing.

  10. NWBO stopped patient screening in response to regulators requiring “something”, with that “something” remaining a mystery for now. Hence, the regulators were the root cause for why the patient screening was suspended.

    The silence for why is deafening at this juncture. That we’re all still scratching our collective heads as to why is indeed strange. An obvious precedence doesn’t appear to exist for comparison which is quite baffling. Very strange.

  11. I’m apparently scratching my head for a different reason. Could be dandruff, but while I’ve gone down most theories, I remind myself this is a first interim analysis. I know DCVax-L well enough to know there is a zero chance we are facing a futility situation at the first interim. Normal continuation is likewise unlikely in that it would be no big deal to announce at a first interim. This trial, imho, was structured to see efficacy at the 1st interim so that they could move towards accelerated approval. A recent post on IHUB presents an article on how the DSMB has gone about suspending further patient intake so that those within the system could get to approximately 3 months.

    LP stated recently, she expects to hit the primary endpoint a couple months after full enrollment. I thought that article found on IHUB was remarkable, because it showed a pathway wherein the DSMB could be the “bad guy” that kept a successful trial blind (for a while longer) to make certain they had enough data for the FDA. Larry Smith brought up in toddy’s article that it is very important to get that data and not end a trial prematurely.

    I think we must then ask what is a premature end? Is it lifting the blind before all 248 patients event, or lifting the blind before the entire 348 enrollment is complete and the last patient has been given their last therapeutic dose (not including boosters) — reaching the primary endpoint? Apparently, it is the latter. I am confident they are not keeping this trial blinded to additionally meet the overall survival analysis event trigger. It will be sufficient, IMHO, that they are enrolled through randomization for the confirmatory trial and reached the primary endpoint. I expect OS will be open label (as a confirmatory trial) from then on. Moreover, there is a UCLA phase II trial no one talks about using adjuvants (and no adjuvants) with what convincingly appears to be DCVax-L. Its data is likely nearly ready for publication. Could this be used by regulators to enhance their efficacy review for DCVax-L? You bet.

    Meanwhile, EAMS, HE and NICE need phase III data to resolve their reviews/negotiations. Did they get it when the documents were recently submitted to regulators? My thinking is that they did. EAMS appears to be a more accelerated process than AA. NICE and HE need the data to finalize pricing.

    So, there is far more than meets the eye to any of this. Trial integrity is first and foremost. What we learned today is that blinded trials can continue on a temporary basis at the bequest of the DSMB. Did that happen here? Don’t know, but I always wondered how they might take some heat off a CEO where a blind needed to be continued despite first interim success. A very able poster on IHUB found that article I cited. If one takes away nothing else from my rambling, consider the DSMB has some ability to keep a successful first interim silent for a limited period of time in order to collect more data and thus take heat off the sponsor for going against an otherwise halt recommendation. Far fetched? Not in this scenario.

  12. Your analysis is logically consistent and well reasoned.

  13. In addition to the above well reason comment it has been a long stated goal (see gov’t. trials website) that an interim assessment would take place in Sept. ’15. In the last earnings release the company made the comment that cash burn was higher then anticipated as more patients were enrolled faster then expected. Did the company accelerate enrollment in order to have enough data not only for the interim assessment but also accelerated approval?

  14. Interesting points.

  15. To the person with the long and interesting analysis above, could you provide a link on the UCLA phase 2 you cite?

  16. The reference to 348 patients is cited frequently and, from memory, I thought that was the figure on the website but having checked today it says estimated enrollment 300 – is this a change to the estimated enrollment or has that figure always differed from the 348 from other sources?

  17. 348 is the correct number.

  18. Appreciate the additional thoughts. The additional “comments” dialog provided good insight to what may be happening.

  19. Larry, have you heard about that UCLA phase 2, or can find out for subscribers what he or she is talking about?

  20. sentiment stocks says:

    300 has been the number listed on clinical since last year. But as Larry indicates, the number was changed to 348 in August 2014. If they had 20 patients per month (minus those who are determined to be rapid or pseudo) in the 3 month pipeline… maybe they could enroll the trial with the additional 48 patients needed and screening would end anyway.

    But… there are those 32 pseudo progressors in their own happy little arm. If the main arm trial shows the correct stat sig numbers at the first IA (or 2nd IA)… the 32 patients’ data gets to be added in. I know we all think now they are not part of the 348 as the 32 were separated out on the slide presentations from the 348. But I suggest it’s still possible that they hit the numbers they wanted to at first IA… thus added in the 32, and they have numbers they need to complete the trial. Just another fun theory I have to throw about.

    I do find it interesting that the trial enrollment in the US still shows 300 as the estimated enrollment… and they have been very busy updating all the clinical site names and contacts… giving them ample opportunity to change that number.

    And the Estimated Primary Completion Date still shows this month. They could have changed that too. And they haven’t changed either. I think they are up to something and I think it’s really good for longs. Not so good for shorts.

  21. Clarification. In the post above dated “September 9th, 2015 at 12:31 am,” on two occasions where I used the term “primary endpoint,” I actually meant to say “primary completion date.” Sorry for the confusion.

  22. I think the 32 pseudo progressors are from the DCDirect Phase I trial not the DCVax-L Phase III trial. So you are mixing patients.

  23. anyone know why we got crushed on Friday??? Hope it is not bad news waiting to come out on Monday…..Hope we hear some good news soon….too many lawsuits…..we need test results to put us back on track…..anyone care to wade in??? thank you….have a terrific week everyone….thank you Larry for good reports….I am holding and waiting to see something, maybe by Christmas….cheers

  24. I can only say one thing; read VERY carefully the answers to stockholder’s questions in the recently filed 8-K.

    I think a hand is subtly tipped. I spoke directly to Les the day this all went down. There was no fumbled news report. He tried very hard to be without emotion in what he said and simply told me to “hang in there, we’ll get a press release out soon”. The fact is someone noticed the “temporary halt” on the EU trials website where as no one from the company did (or probably anyone else for that matter) and started talking loudly. What was it that triggered someone to look at that website and then make an assumption from this? Someone let something slip (good news) I feel, and the shorts jumped on it pronto, putting out the “Halt” mis-information/interpretation. NWBO was hamstrung at that point because they had to respond without tipping their hat to any good news they felt might be occurring.

    Holding information while regulators are sifting through data is quite responsible, as tipping things one way or another is risky under the SEC scrutiny. With all the allegations by short bloggers from previous press releases where NWBO was trying to give investors something solid to hold onto I can completely see them trying to reserve word until they felt it was ok to do so. In this particular instance I feel it’s most likely possible that someone “spilled the (good) beans” and it got around to the shorts before it hit the longs.

    Things get out in these trials, there’s never a point when someone’s not saying something. I can see a scenario where people just keep living, feeling great, back to a healthy life; the rumors start to spread within the cancer patient community that this stuff is working. The voices start getting louder and louder and in an attempt to hold off a patient led campaign to get this drug to market the regulators feel they’d better take a look quickly to see if there’s something to the gossip.

  25. As to “why we got crushed on Friday”; I feel it’s just the market sentiment right now. People are panicky and NWBO still has mostly retail investors who can react just like someone at a black jack table in Vegas, move their money out of one thing trying to catch a hot stock going up in a crappy and volatile market. They’re skittish and can follow Herd trading based on word of mouth and blogs.

    I used to react much more to inane and irrational/emotional cues when I was a younger investor. I started investing my lawn mowing money back in the 60’s and early 70’s. When the economy was tanking I was buying more, while putting some in savings. By the time things corrected I had enough money to buy and fix up a house, sell it, use the proceeds to start a business, buy more stocks, sell it when I needed capital for other things like going to medical school, and buying both solid companies and volatile biotech’s.

    I’m a physician and have read almost all the studies I can get my hands on. I’ve looked into Linda Powers, seen her resume’ (which is almost unbelievably solid and amazingly impressive) and studied every move this company has made for the past 8 years. I believe they’re the Tesla of Biotech to be quite honest and have not only relentlessly and solidly designed and tweaked their processes but have also built, in the background, the necessary manufacturing systems, business infrastructure, and technology to make this an incredibly successful and long standing pharm corporation.

    Linda Powers is a genius in my mind. I think she had her eye on this company and used her skills and brains to put them in an exceptionally powerful position to be on the front line of this technology.

  26. Thank you whomever you are for the above posts and comments and opinions….You now sound spot-on after today’s news that Linda will be presenting on Wednesday in London…..I do hope it is good news…..I have picked up some-more shares today with the dream that echoes your opinions….I am sooo thankful that someone did get to talk to Les…..There are sooooooooo many irons in the fire with this company……collaborations, pricing, part 2 in the UK, hospitals in the US and in various countries for “D”, more evidence from the “L” group that is in the compassionate arm, more evidence from the “B” group in the “D” trial, just to name a few that I can name….So, I will listen in on Wed. and stay tuned to the progress I hope we are making in cancer research and treatment….thanks go out to all, Larry, for your articles and the comments of your subscribers….Wish I had something smart to add, but I am just a cheer-leader who hopes and dreams that DC science and NWBO’s technology band together to help people with cancer to get their own bodies to join in the fight against it without the terrible side-effects of some other treatments….cheers, and I’ll add more after Wed. presentation, although I think Larry will be out with an article in short order….cheers,

  27. Hi Larry,

    Can’t wait to hear your analysis of Linda’s presentation this AM…..I thought it was fantastic…

    Now we also hear that Max will present later today in NYC….. This presentation should

    be a real eye-opener…… I think things are going great at NWBO….what do you think??

  28. NWBO seems to be entering into a crescendo phase where good news, if it comes soon, could lead to a stock price explosion: if it doesn’t come soon there is going to be fierce downward reaction. Frankly I was rather disappointed with LP’s presentation today – seemed like just a bit more of the same data as in the last presentation. I didn’t hear any mention of the halt in new patient enrollments in the phase 3 DC VAX-L trial. I was hoping to hear some explanation for that but I guess we going to be teased on that score for a while.

  29. I happen to want to echo the above post……1. what is the screening halt about and where is happening??? Is it in all locations or only Germany??? 2. If no new news comes out in say, the next 2 weeks, people might lose confidence….. 3. I thought the news looked good, but was confused that some was referenced to Feb. 2015 and some to Sept. 2015…..3. I am disappointed in Larry that he has not written up his knowledgeable opinion on the presentation….4. Just as an aside, I really resonated with the word, “tease”. IMHO Linda and Les tease us shareholders with so many irons in the fire, but it seems to take forever to get to the bottom line….It could be that she is waiting for the FDA approval of ‘L’ to come out with pricing, UK approval for its special exemption, the collaboration, the hospitals that will be testing ‘D”….I know for a fact if they wanted to make the news, they could bring out the patients that have benefited from the “B” formula of “D” and are healing and living longer….They did with the National Geo report….How is that man doing today??? So, if anyone reads my post here, I do feel teased by NWBO,

  30. I agree with the above post, regarding feeling teased. Within the next few weeks, NWBO will have to come clean regarding the halt. If the don’t by the end of october, Im out.

  31. You’re way out of line calling Larry out on his own website and saying you’re “disappointed” he hasn’t responded within a timeframe you find acceptable. This is the best and most timely info on NWBO you’re going to find…and it’s not even close. If any new potential subscribers are reading, please disregard the comment above. Smith on Stocks is an excellent source of information and I’m betting the vast majority of us are extremely thankful.

  32. Everyone who comments on this site is a paying customer, so they should be free to state their opinions and concerns. However, it is not Larry Smith that the commenters are “calling out”. It is the management of NWBO who issued the non-informative press release without any subsequent follow-up. Perhaps they are constrained by the unnamed regulatory agencies from further comment. I’m willing to give them the benefit of the doubt. But I’m still distressed by their complete silence.

    Incidentally, I’m the commenter who first used the “teased” word above. I was referring to the NWBO management, not Larry Smith.

    Bob Roig

  33. A couple comments;

    1 – I understand everyone’s frustration with awaiting good news, or any news from the Phase III trial, but I dont understand why the finger gets pointed to L. Powers and NWBO management for “hiding” or keeping everyone in the dark. This is a blinded phase III trial, so there is nothing to update, other than when the endpoints, or mid-trigger points are met. They legally are not able to give out this information, and probably (or legally) are not supposed to even have access to that information. Once the endpoints are met, only then are they able to give an update.

    2- This is a question for Larry, very much like the Direct Phase I trial, would NWBO have patients (and perhaps they are paying patients, or those from Europe) that would not be included in the Phase III Blinded Trial, to which NWBO is able to collect data on. I would think that patients that do not meet the trial criteria, but perhaps pay for or perhaps NWBO has funds set aside, to be treated with DCVax-L and allow the company to monitor them. If that is the case, that data would be available, and perhaps provided to investors such as Woodford in order to attract institutional investors? Is that something that is done, and if so, would NWBO have done this?

    3- I believe that L. Powers to be very intuitive and as I have mentioned on numerous posts, I feel she has provided a business spin to her strategies with NWBO. First off, keeping the company independent of big pharma so that the pay off is that much larger, and the way she redesigned the phase III for DCVax-L, even though AF, and all the shorts criticize the PFS as the primary endpoint, what it does, in my mind, is provide the Phase III trial a higher probability of success, and here is why:

    – PFS for IMUC, DCVAC, and numerous other immunutherapies, all seem to show extensive PFS, particularly in subsets (IMUC phase II). This means reaching the primary endpoint of PFS shows much more promise than the difficult OS as a primary endpoint. Moreover, if the PFS primary endpoint is met, but the OS endpoint isnt met, or slightly under the 2 or so months, would the FDA not approve something that could be beneficial for various patients in those subsets? Moreover, the OS average from the DCVax-L Phase III Control patients, could be actually 1 – 2 months greater than the SOC OS (though this can not be measured as the control patients roll over to DCVax-L if tumor progression occurs). So NWBO could even argue that the secondary endpoint, OS, may not be a true reflection of the improvement that DCVax-L provides, since, if DCVax-L truly works, it could increase the survival of some of the control group as well.

    I truly think that the way this trial is designed, it has many chances of success, particularly if PFS is improved, which has been one constant seen in immunotherapy.

  34. The issue is the halt in new patient screenings, announced but not explained.

  35. Anyone interested in ( JMHO), a real analysis of the “halt in screening” that is really for all sites, not just Germany, I would urge you to go to the Yahoo Financial page and go to the NWBO quote and the message board in which someone has taken a lot of time and effort to break down the possible reasons for the “halt in screening”…..He (sorry you should really read his efforts and not my summation of them) says it (the DMC) has halted screening (which is the same as saying they are not enrolling anyone from that day forward till something happens to open enrollment again) because it
    A. works so well it would be un-ethical to continue to give patients a placebo, or B. it is not working and no one should get something that is not working, even if it not really harmful for them…..Since the compassionate use patients show ( over and over), (see ASCO and then the follow-up in NYC and the UK), he posits it is working and they (the DMC), are going through the correct process of un-blinding the data they have now and working out how to move the treatment forward in the approval process….I think he said that takes about 3 months from the time of the stopping to the announcement of un-blinding and then more time for the approvals to get organized and given….so, 1 and 1/2 months are in the books since the “halt of screening” so maybe in the next 6 weeks we will hear an announcement about the interim results of the blinded trial of “L”….Hope so….better you go to Yahoo….Could you do that Larry and give your considered opinions???? I trust you more than anyone I don’t know on Yahoo, even though I like what they are saying….Cheers, longNWBO

  36. 10/16/15……Hi Larry and anyone who reads this….Please comment on todays almost 30% sell-off…
    I sure don’t have a clue….Did AF or some publication say something negative???? Did the company put out bad news??? Is Linda sick or something internal or in Germany or the UK or some patient get ill from our treatment??? Please someone, shed some light on today’s huge volume and price decline that is the exact opposite of what I have been waiting for….Thank you….long NWBO

  37. I’ll speculate. It didn’t seem to be AF. In fact, he was asking the same question as you.

    When I started digging I found a SEC filing on NWBO’s site dated October 8th. I’m not sure if the file was posted on the 8th or later. I’ve pasted the entire contents below:

    “Shareholder inquiry: What is going on with the change in completion date of the Phase 3 trial on Is there a new change or delay in the trial?

    Company answer: No, there is no new change or delay in the Phase 3 trial. In all of our public presentations all year long, we have stated that we anticipated finishing the recruitment this fall, and reaching the primary endpoint around approximately the end of summer or September of next year. The profile was very out of date, and the change of date in that profile from September of this year to October of next year simply conforms the profile to the information we have provided publicly all year long, plus about a month of cushion to take account of the temporary hold on new screening for the trial as we announced in August.

    We are also updating the profile to correct the number of patients. As stated in all of our presentations for over a year, the total enrollment will be 348. The profile was very out of date in listing 300. We will simply be conforming the number in the profile to the number we have long presented publicly.”

    Personally, I take issue with this. Admittedly, if they are still enrolling new patients or need to, then they aren’t going to get data for awhile. However, I don’t recall the company giving any dates. I also don’t recall Larry changing his expectation from 1H2016 but maybe my memory isn’t so good.

    I also think that this might be a hedge fund attack. Volume has been very low of late, especially this week through early afternoon today when the stock plummeted on several million shares sold (10x “normal volume” for this week). Now small investors will have the weekend to panic and may continue the run come Monday morning.

    BTW, Woodford didn’t add shares in September and presumably hasn’t been in October since they are presumably going to be purchasing a big pile of shares directly from the company in the coming weeks. In fact, they would seem to be in a position to benefit from today’s drop as presumably that will impact their purchase price. I don’t think Woodford would do that given the level of detail they provide about their trading activities (the recent 13D and their monthly holdings report on their website).

    I think this is either the hedge fund wolfpack looking to cover their short or just going on the offensive against Woodford who has to decide if his new fund wants to double down on NWBO. He clearly knew that NWBO needs money and that the stock will go down if he doesn’t provide it. He also presumably was well aware of the naked short selling activity and knew that it could and probably would get nasty.

    I added a few more NWBO shares today. I hope Larry can shed some light on this situation.

  38. I just want to thank you for your detailed and complete response to my above questions….I REALLY appreciate it…..I am soooooooooo confused about when we can expect full enrollment for the “L” trial, maybe an “interim efficacy” announcement, news about what we are submitting to the FDA for our ‘D’ phase II trial, German activity for HE patients, part 2 for the Brits application, a partnership and on and on and on….Money is a huge over-hang….So, I am sitting tight, buying more distressed shares….feels like a “fire sale”……So, I wish the management, (Les), would put out some kind of reassurance to me (us) about everything is really ok and on track and stay tuned, or whatever….So, again, thank you (whoever you are) for taking the time and effort to break things down and give some plausible explanations to the disaster of last Friday….HOPE for a better week….cheers


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