Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
chinatown1980,
I'll leave Dr. Linda Liau, AVII or Pyrrhonian the chance to answer your concern about what happens after the 248 events occurs. Best wishes.
chinatown1980,
The "hopefully if they didn't get anything" comment by Dr. Linda Liau is a lament about the trial length and not about the desired patient outcomes. While it is possible that some patients chose not to cross over to the treatment arm this was not very likely at all do to patients knowing that crossover meant they would now receive an experimental and perhaps life changing treatment. This statement was Dr. Linda Liau's way of saying she wishes that a standard comparator arm could have been used but of course this was impossible as a standard SOC placebo had to be made by NWBO for this trial. As you know, SOC in the ICT-107 and Rindopepimut trials appeared to have been active so no help there either. Best wishes.
chinatown1980,
The biggest risks are always investor discipline with regard to risk tolerance, allocation (divirsification), hedging and time related opportunity loss. As Rkmatters pointed out recently, this trial appears to be designed to give it every chance possible to succeed and that can lead to a time consuming wait for trial completion to occur especially if slow eventing, PFS and OS, is the issue. I believe we have reached or passed the point that Pyrrhonian said 248 PFS events should have occurred so that puts us at a crossroads. Every day from here on out favors the patients and DCVax-L based on his assessment and that assumes the interim passed and was not reported. This does not change the need for cash which trumps all until positive news about HE or the Phase 3. The start time for the combo studies seems to be predicated on at least one or both of these 2 announcements being made. When the announcement we are all waiting for comes then whether it is positive or negative for the company, the biggest risk to any investor is in the plans and precautions they laid out for such an event. Best wishes.
iclight,
Thank you for using the word "probably" in your last post. I respect your opinion.
Many bear arguments have at the heart of them an underlying sense that Linda Powers is being deliberately deceitful. This may not be the focus of any particular point being expressed but this cloud engulfs it. Until we actually realize how the relationship between Linda, Cognate, NWBO and Toucan benefits long term investors with a successful trial, the cloud that has been created by less than fully explained actions and the inuendo surrounding them will not be lifted and the share price will suffer. With this I agree. It is the dagger held to the throat of longs that will not be removed until and unless trial success is achieved. I am of the opinion that Linda has been and is doing everything she possibly can to provide for trial success and that means using all available options to de risk the trial and provide positive news for patients and investors alike. I also believe that the backlog of news that will be released could be enough to create a tidal wave change of publicity that NWBO must be made ready for and they have been quietly been making preparations for just this. Best wishes.
sentiment stocks,
Thanks for bringing it back to the top. ;)
sentiment stocks,
Don't forget the supporting statements to the "..it seems like everyone's living longer" comment that point out the slow rate of eventing and potential of additional therapies which could be used at crossover or initially with treatment in the future to increase response rates.
HappyLibrarian,
A document dump would be bad but what we are talking about is more related to operational updates not documents. A document dump does not include a summarized conclusion and would lead to a massive scramble for the needles in the haystack which would eventually be found anyway. The folks Linda brought on would likely be willing to cooperate in that regard so a document dump is a very very unlikely scenario as it would immediately draw attention. Nice try though. Best wishes.
exwannabe,
I do not disagree with your assessments with regard to my post. The reason I stated the points I made as I did was to highlight 2 important points about this trial. The first point is what you pointed out and that is that a blinded comparator arm is needed for a registrational trial. There are some who have stated that this trial is not registrational and the way I presented my post demonstrated why some have come to this conclusion which is wrong. There is, as you state, a controlled comparator arm directly tied into this trial. The second point I was trying to make is that there are 2 trials that will potentially be tied into one final set of results which by default adds a third arm of comparative results for a specific subset of patients within a more general patient population. Best wishes.
iclight,
This trial only has a true control arm for PFS. For OS there are 2+1 comparator arms which are expected to act as control arms to some extent. These 3 comparator arms are SOC plus DCVax-L before recurrence or pseudo progression, SOC plus DCVax-L at recurrence or pseudoprogression (crossover) and the known early pseudo progressors in the separate trial whose results might be added into the main trial. The "living longer" statement mainly applies to OS outcomes but should/may also be related to when DCVax-L treatment begins and, therefore, to PFS as well. Since you do not know whether or not the PFS trial endpoint has been met or not or whether early treatment is superior to later treatment at recurrence and or pseudoprogression with regard to OS, your tacit claim that DCVax-L is a failed therapy (" waste of resources on DCVax") is an expression of foolish bravado at best.
Your assumption that DCVax-L is a failed therapy is counterintuitive to the documented evidence of synergistic effect noted between various types of previously failed therapies such as chemo/radio and even checkpoint inhibitors and DC therapies. Synergy will be awarded to DCVAX treatment by appropriate measure with regard to OS. To obtain the best chance for approval NWBO would need to assume PFS is only close to hitting statistical significance at 4 mos benefit and wait out OS results before unblinding. The 2+1 comparator arms will help distinguish where benefit is most likely to be found. None of this understanding changes the price direction until it is validated in this trial but when and if it is validated, being right about the price direction the day before won't save anyone at the opening bell. Best wishes.
sentiment stocks,
They sure have a strange way of demonstrating that they want and hope the best for the patients in these trials especially since they all seem to be living longer than originally anticipated according to Dr. Linda Liau. Best wishes.
Rkmatters,
That is correct and repricing of outstanding debt for services rendered is also correct by kabunushi. There was some discussion a while back about why Mr. Woodford wanted the outstanding debt paid off to Cognate. If he came to the conclusion that share price would diminish over some period of quiet time he would obviously not want debt converted to shares at a much lower price due to MFN during that time right? Looks like the quiet time is taking even longer than he expected. Best wishes.
BuyWhenISell,
Pyrrhonian's main argument is that the technology (whole tumor lysate loaded DCs) is older and ineffective as used in the Phase 3 trial protocol. Rkmatters and others agreed that proprietary info is not discussed in the protocols so to draw any firm conclusion about the technology being used is premature guesswork steered by evidence guided by known parameters being used to make assumptions about technology that is obviously proprietary and unknown. This argument along with downward share price direction caused by management's silence in the face of accusations about potential self serving financial agreements between related parties gives shorts the upper hand for now. Add in the constant need for new financing with related dilution from someone other than the person seen as a strong backer and the fact that other trials by competitors have failed and you have the recipe for where we are now.
AVII believes the trial will be affected by a greater number of pseudo progressors in the main arm than expected and cause the primary endpoint to fail thus creating a high probability that the trial as a whole will fail. Rkmatters, Flipper and others are still not so sure that PFS will fail but have also demonstrated how OS can be improved by a restart of more frequent dosing at crossover. This is also consistent with Dr. Linda Liau's statements about all patients apparently living longer and lack of eventing being a concern with regard to length of the trial.
FDA opened the doors to investor speculation when they peeked at checkpoint inhibitor data before the trial was completed and stopped the trial for efficacy. Regulators are obviously actively involved in the DCVax-L trial and the temporary screening hold has now been in place for over one year. We are obviously waiting for something definitive as FDA is want to let bad news remain undisclosed. With the numbers they do have, FDA has plenty to determine and announce futility if that were the case which seems highly unlikely given the length of time involved. Since regulators have apparently placed the temporary screening hold on the trial the onus is on them to announce why if the company is not required to do so. Best wishes.
Adam Feuerstein,
Let's try the new anti "Adam spin" game. Adam asks Merck and Bristol "Are you collaborating or partnering with Northwest Bio...?". Why would you ask what we already know? There has been no public announcement that an agreement is formally in place so we already know there is no final signed agreement in place and actively triggered. You offer no new information because you know there is none to be had. This would be the same as me saying that "Adam Feuerstein proves that active negotiations between NWBO, Merck and Bristol could be taking place." You realize, of course, that your opening denial about the possibility of ongoing negotiations is an appeal to authority which you do not posess. Some of your readers readily grant you this authority anyway because they do not take the time, like you carefully did, to separate statements with different paragraphs, which separates your inuendo from the actual truth.
I am in for the long haul here but September is a big month for biotechs because of renewed regulator decision activity and it seems you are staying tuned. Interesting how you just can't stay away. I guess you have succombed to the Powers that be. Lol. Best wishes.
chinatown1980,
Don't get too disappointed by that wording. Sometimes authorities don't want to reveal too much about their investigstions. Sometimes they have been actually known to point attention in a different direction just so the folks they are really interested in will keep their guard down. Best wishes.
chinatown1980,
Earlier this year a Supreme Court case sought the right to have cases against stock manipulators decided in state courts where a stricter pre-existing code of conduct is held. The Supreme Court upheld the right to return these cases to the state courts and more stringent laws in place there. I misplaced my notes but another small biotech like NWBO won their court case against manipulators and this now appears to be the beginning of an ongoing saga in state courts. In a separate matter, Goldman Sachs received a small fine and a cease and desist order with regard to what is essentially naked shorting. They also had another matter come up against them recently that is keeping their name in the news for the wrong reasons. If I can find my notes I will give you more details at a later date.
By the way, the FBI is also working on at least 3 major fraud cases according to the person who first tipped off folks abut Bernie Madoff. One of these cases is said to be much bigger than the Madoff case. Having bagged Martin Shkrelli sp? and an obvious eye on people he knows, the question being begged is who might be next. Best wishes.
Dan88,
As you allude to, and I also believe, we are waiting for an event driven end which may also be time oriented. In other words if less than x number of OS events happen by y time then regulators may stop the trial for efficacy and ethics depending on OS separation noted between arms. The trial could very well drag on if there is no ethical reason to stop it, ie minimal separation in OS between arms. I think this is unlikely which is why I believe a time element is involved. Regulators may be peeking, especially if they are interested in getting the trial stopped because the separate pseudo patients and missed pseudos in the main arm are doing exceptionally well.
Rkmatters,
The recommendations from good oncologists and especially neurosurgeons who work with good radiologists is quite different than what could be found with regard to VICL when I was watching that one closely. I have no problem with those who say they are watching closely here because I did the same thing with VICL but stayed out because the evidence and the science was simply not compelling enough. The oncologists commenting were also not convinced or even close to being so. NWBO is a different story all the way around as far as researchers and doctors opinions are concerned. I wonder what Stand Up 2 Cancer will show this year from all the more recent success stories. The show will be live on September 9th at 8 pm, 7 pm central time. Remember a certain employee of Nat Geo by the name of Allan Butler? Best wishes.
chinatown,
I'm pretty sure that the protocols shared show that all benefit from additional treatments will be granted to DCVax-L. That said, they certainly could look at ascribed benefit to each method tried based on their trial approval benefit to patient population and ascribe only the synergistic difference to L as a comparison. As discussed by flipper44, Temodar may have some short term benefit but hurt long term benefit as memory T-cells can be depleted. Bottom line, synergy is a very, very good thing and even Pyrrhonian has stated that 248 PFS events should have happened by now. I am guessing about 200 deaths would also have happened if no benefit was being observed. If the eventing is much lower than this and has been pointed out to regulators then FDA has had about 1 year to verify this and come to some conclusion. One year is a long time in a disease where MOS might be expected to be about 2 years to 30 months (outside chance) for this group.
sturmndrang555,
No need to purge all of your expectations for justice, just adjust your time expectations. Some very important legal victories have been won recently but the ramifications will still take some time to play out. I have no doubt now that the external investigation is heating up quite nicely and results from that investigation will help bring needed change to the investment community. NWBO history is probably just one of many that will contribute. Best wishes.
AVII77,
I think Rkmatters is just catching a little more of the skeptic's tone in your post than intended. I think we all appreciate your balanced bear outlook as the voice of reason with that viewpoint. Best wishes.
exwannabe,
Well stated. Being a well balanced investor matters at all times. CherryTree1 is right about how missed opportunity or poor appropriation feels though and this is where sober mindedness and discipline comes in to play. Best wishes.
iclight,
"BTW, those that aren't and crossover should know based on the companies (sic) own data that DCVax has no effect on established tumors (that's what progression is)."
This is a perfect example of your lack of understanding concerning synergistic effect. You see, there are multiple studies that have shown that DC treatments actually repotentiate failed treatment regimens like chemo and radiation. If you have been following the discussion from the beginning you could go back and pull those studies up. Just a few days of posts back there was plenty of newer evidence of this affect shared by another poster. BTW, tell all those patients that Dr. Linda Liau said were living longer that they are just dreaming and aren't really alive. I am sure you can convince them that they are just a part of the Zombie apocolypse lol. Best wishes.
Rkmatters,
Looks like they were looking for ~20% pseudos and 10% delayed confirmation progressors based on the original 240 patient enrollment numbers. The 3% mentioned does not even reach the 4% historical mentioned for 5 year survival which is probably mostly from younger methylated mesenchymal, neural or classical patients with good starting scores and near total resection. The bottom line is that a 3% pseudo rate was not expected by NWBO and most neuro surgeons and radiologists would probably not confirm seeing a rate that low either. Best wishes.
Rkmatters,
There seems to be an awful lot of "forgetting" lately. We need to put together a report of all the things that need to be remembered and then just punch a single cue up for retrieval. I don't mind the discussion around the need for financing or even what the ongoing silence might mean but all the points already proven that keep popping back up should be shot down quickly by reference to older discussions listed by sticky topic above. Thanks for taking the time to do the leg work until we get that taken care of.
iclight,
At crossover patients have the opportunity to receive DCVax-L treatments but this does not preclude them from being able to use checkpoint inhibitors along with this treatment. The open label nature of the crossover allows for a lot of experimenting and that is what many are failing to understand. Patients are living longer than expected and DC therapy has carryover effect that causes synergy with treatments that previously had lost their effectiveness. The sooner you figure out how the impact of synergy affects this trial the sooner your comments will align with the understanding of the scientific community. Best wishes.
Rkmatters,
Just wanted to add to your comment a litlle. Improved binding is determined mainly by better fit or stronger polarity(think magnet vs electromagnet). Better fit can be found with separating out high affinity T-cells from the rest. Greater polarity can be achieved by processing correctly. The right combination of conserved (common to many or all cancers) antigens and neo or newly created variant antigens will create a robust immune response with immune memory as long as the inhibitory effects of certain macrophages, Tregs and other cells and signaling are held off long enough to reach the tipping point. Checkpoint combos and or tighter spacing of properly activated DCs appears to be the key to achieving this outcome. We wait to see. Best wishes.
iclight,
Guess what controls the macrophage effect so that CD4+ and CD8+ T-cells can have a chance and then loses control when no longer around leaving checkpoint inhibitors the opportunity to take over? Bingo! We have a bunch of winners and it is more than investors or NWBO. It's the patients and their families. Best wishes.
Steppewolf_Speaks,
There is a bit more of a gamble here that should be aknowledged by shorts. If the bigs expect any news they will wait until about 3 weeks prior to really start a solid buying trend. You have seen this before so you know what I am talking about. Yes this needs to be balanced out by the need for financing which shorts have had a hay year with but at least suggest a better risk assessment plan if you are going to give investing advice. Best wishes.
exwannabe,
I think you are missing my point which is this comparator arm of which I speak does not need to be officially set apart for statistical purposes because it basically has already been acknowledged to exist as a separate group to some extent by way of manufacturing upgrade approvals and older resection techniques. Any resection technique improvement benefit should be clearly seen in SOC between vanguard and newer patient populations without any other confounding factors so no need for concern there. NWBO has also told us in general terms how the product has been improved by automation changes. Equal or better is the only bar regulators require and those tests were passed.
Dr. Linda Liau gave us the ~24 mo MOS expectation for newer GBM patients which takes into account newer resection and imaging techniques. The expectation for DCVax benefit was added onto that in the protocols which puts their expected MOS at about 30 mos or more. With all patients appearing to be living longer than at least the 24 month mark and perhaps beyond the 30 month protocol mark (thus causing expected trial OS eventing delays), the previous trial 3 year MOS mark seems to be within range of being reached or surpassed. If 36 mo MOS happens compared to a 24 mo to 30 mo MOS for SOC then I guarantee you FDA will be looking at early vs late treatment patients but mention of this in any part of their final analysis with regard to approval proceedings would be doubtful unless there is a striking MOS difference. As you say, that would be prospective analysis even if it looks very compelling.
Next we have the very real possibility of adding in the pseudo arm results to the entire cohort to bump up the overall results if the main arm is approved on its own. What do you think the MOS would look like after that? Do you think checkpoint inhibitors might have been given to crossover patients by big pharma as a way to pretest synergy before they start a combination trial? That would be a cheap way to look under the hood right? What if this combo was working really, really well so that all patients appeared to be living longer and it was causing the trial to be delayed due to a lack of OS events because the company wants and perhaps needs to wait for OS eventing. Win win for big pharma right? It buys time and keeps NWBO stock priced cheap. What if a serious adverse event or 2 caused by a checkpoint inhibitor crept into the picture? How would that impact Phase 2 combo plans and the Phase 3? I will be the first to admit there are plenty of questions that are begging for answers but I think the vanguard group will help answer some of them in due time. Best wishes.
pgsd,
Thanks and best wishes.
exwannabe,
The trial does not become flawed just because you have an additional comparitor arm added in during a trial resizing, it becomes an improved measure of outcome. Kind of like early vs late treated patients as long as the new manufacturing process compares equal to or better than the old process. The newer process appears to be better so why the beef? There is a clear timeline division so no confounding. Do you really think that FDA will not side with better patient outcomes if they have statistically significant beneficial OS outcomes between these 2 groups or between treatment and SOC plus crossover even if PFS was borderline?
Evaluate,
I had trouble at first reading this cyber code for math with other reading I had done. Just so all are clear, Rkmatters was attempting to show 10 to the 11th power or 10^11 or 10×10×10×10×10×10×10×10×10×10×10= 100,000,000,000=100 billion (cells) being reduced to 10^9 or 1,000,000,000 (cells). The carrot sign is used to symbolize upper placement of numbers for powering purposes. When no carrot is used the numbers are often run together as a type of shorthand code and can be confusing. Best wishes.
Pyrrhonian,
I would rather be called delusional by someone who thinks I am wrong because of current circumstances and end up being right in the long run than be called one of the best analysts of a company on the positive side by a respected analyst then switch positions and end up being wrong. Time will tell. Best wishes.
sentiment stocks,
Well said and thank you for sharing your due diligence with all here on this board. Best wishes.
AVII77,
Thanks. One of the things I really like about this trial, and I commented to Larry about this on Seeking Alpha quite a while ago, is that the trial design really seems to focus on achieving the very best outcomes possible for the patients involved. There is so much built in flexibility that points to keeping options available for patients no matter their financial situation that I would support this trial just because of this. As Dr. Linda Liau said, though, this does not help the trial end quickly. As an investor in the humane care aspect as well as the science of NWBO, I am more than willing to bide my time while waiting for the official outcome. If FDA is challenged by results to find a way to validate a new approach to awarding patient benefit to a novel treatment that helps patients live better and or longer with an insidious terminal disease then all the better. Best wishes.
AVII77,
There remains the possibility that because these combination treatments being discussed will be most likely given in alternating fashion and the Phase 3 crossover most likely had such alternating treatments given in some cases in a clinical trial setting, that the argument can be made that safety is already proven to a sufficient extent to allow for the Phase 2 designation. Duke would not necessarily have access to this information and would therefore need to submit as a Phase 1 especially since the priming mechanism and activation is different. Best wishes.
Rkmatters,
Spacing of treatments and or adjuvant therapy such as checkpoint inhibitors is absolutely critical. Properly activated DCs can and do regulate the tumor microenvironment for the short time (weeks) that they are there before their life cycle ends and they are replaced by uneducated DCs which do not have the same capacity. T-cells by themselves do not have this capacity and must have exposed antigens to target and this includes memory T-cells. This is why existing T-cells, including memory T-cells, spring into action once activated DCs show up on the scene. Activated DCs help expose buried antigens with their signaling but only for a short time before their life cycle ends. Checkpoint inhibitors add to the time that T-cell populations are able to remain active before additional tumor suppression activity begins to shut the entire process back down. Once the proper spacing for alternating treatments is determined for L, I would venture to say that it will end up being weeks apart, then results will be quicker and much more readily observed as continuous action.
austinmediainc,
I try not to draw too many conclusions but as you note I do try to think of the possibilities because I like to figure out the dead ends and continue to pursue the still open avenues. Those who do not see the possibilities often give up too soon and I am not speaking simply about investing here because investing requires a disciplined approach in order to be successful over the long term. The approaches can be different but discipline is the key to any approach. You rightfully have warned those who are taking a much shorter time frame approach to their investments as have others who have been criticized for their views. I look for forward steps in the science and operations which is different than the month to month focus on financial condition that captures price support for most early biotechs. Thanks again for your contributions here with regard to valid investor concerns. Balance is always good. Best wishes.
Rkmatters,
I am seeing what you see for where and when it is needed.
strmndrang555,
Linda mentioned "the gentleman from Roche" a couple of times in one of her presentations a while back so there seems to be a connection there. Roche needs something new in a big way as the are heavily weighted in oncology and will face serious challenges if they don't find a way to get up front with the newer technologies quickly. Best wishes.