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.
sentiment stocks,
There are some very interesting ideas that have come to mind for me over the course of my research into dendritic cell function with regard to the entire immune response. I believe that one of their functions may be missing or limited when DCVax-L is given initially which may be something that NWBO figured out was a necessary component of a more complete immune response. You see, normal circulatory DCs are designed to move towards areas of inflamation in the body as the initial responder. Once at an inflamatory signal site they can assess the situation with the specific assay of signalling and environmental conditions that they encounter there and begin additional signalling themselves. In this process they are normally able to regulate macrophage activity and function to some degree. Cancer cells also have the ability to affect function of macrophages. If these sentry type DCs do not have the capacity to induce proper signalling at the site of inflamation (unprimed or improperly primed circulatory DCs) due to confounded signalling caused by cancer or leave the area of inflamation too soon due to genetic changes from environmental conditions, their influence is lost. Their antigen presenting function on its own also loses meaning as Tregs maintain or regain control. DCVax-L skips around this initial scout stage by injecting primed and matured DCs into lymph rich areas away from the hijacked tumor draining lymph zones which then activates and perhaps reactivates the T-cell response. Direct essentially has the ability to overcome this lost step by having DCs being placed directly into the tumor environment so the scout signalling step is not lost. While priming of the entire immune system with a tetanus vaccine before treatment or using viral vectors along with treatments to essentially prime the cancer environment to drop it's guard show promise, getting primed DCs to stay long enough or renewed often enough for a cascade effect to develop seems to be the ideally safe way to overcome the tumor environment. The other option is to have alternating inhibitor treatment to extend the length of time that educated killer T-cells can remain unhindered.
I have seen the comments by researchers made about the mouse study which seem to indicate that checkpoint inhibitor build is relatively quick which would lead one to believe that this is an inevitable consequence of DC therapy. The way the comments are written also lends credence to this idea. I still wonder if the DCs utilized in the mouse study are influenced by the more rapid metabolism of mice and move out of the cancer zone more quickly than in a human host which would lead to this aforementioned conclusion. In other words one might ask whether or not more frequent dosing alone might be enough to overcome immunosuppressive responses. This would be a good question for the scientific advisory board to look into if it has not already been satisfactorily answered by data. Best wishes.
sentiment stocks,
Bravo. You sure know how to use the bully pulpit. Best wishes
koman,
Allan Butler is the only patient I know of who has received both DCVax-L and DCVax-Direct. Go to the Linked in site for Allan Butler and you will see that he has been Vice President of Development and Special Projects, with focus on NGT (Nat Geo Television) from 2013-Present (3 years 9 months). His Nat Geo Stand Up 2 Cancer video stated that he had been diagnosed with stage 4 pancreatic cancer and he was out of options until his participation in the Direct trial as validated by cameo of Dr. Vivek Subbiah. You can doubt all you want but as of right now the L/Direct combo is 1 for 1 or 100% effective and Allan Butler is living proof. Best wishes.
koman,
Maybe you have not been able to understand what the evidence of extensive necrosis found in some of the tumors injected by Direct is most likely related to and why. You may also not know how method A and method B might be similar yet seemed to show different outcomes. There are clues and those clues point to better specificity. Remember what Dr. Prins said about Dendritic cells paired with monoclonal antibodies LIKE the checkpoint inhibitors. Engineered T-cells are primed with monoclonal antibodies but having one part of the immune system over activated often leads to undesirable consequences. Dendritic cells used to prime T-cells won't have the same problem.
When you say "Any claims of efficacy for Direct are unproven..." You are correct with regard to final clinical trial approval but not with regard to actual clinical trial evidence based correlations. If you can show me a legitimate obituary for Mr. Butler, who had terminal pancreatic cancer, was given Direct and was last known to have returned to work at Nat Geo, then I will stop pointing to evidence based reasons to expect efficacy. If you can't produce this proof that it does not work in his case and perhaps others as well then I will assume you have less evidence that it does not work than I do that it does especially in light of inappropriate spacing, dosing and optimum method. Best wishes.
DoGood DoWell,
I have a feeling that a grapefruit juice truck might show up to make a special delivery someday. LOL
koman,
Grapefruit juice consumption can inhibit metabolic degradation and erradication of active ingredients in certain drugs. This can lead to higher levels of the drug remaining in the system at the next regular dosing leading to overdose. There are also some instances of Direct interactions between drug and juice. There are, however, very good reasons as related to evidence of MO why DCVax-Direct works much better on cancer than grapefruit juice and very few understand this. This can lead to statements like the one being discussed from those who believe they know better than others, including researchers, how to explain results. Best wishes.
afford567,
Your honesty and angst are both appreciated as angst from faithful longs can lead to corrections like what we just witnessed with the NASDAQ compliance agreement. Granted, bigger guns than ours may have been the primary motivating factor but nonetheless the angst itself was perhaps more visibly expressed on an ongoing basis by lesser hands and required resolution. Best wishes.
sentiment stocks,
Agreed and I believe lattices has a well thought out strategy with regard to time vs risk. Best wishes.
afford567,
I have not yet read Larry's latest piece but as you describe the attitude of uncertainty it is written in it sounds about right for where we are at with blinded data points. I believe in the science and experience advantage that UCLA and NWBO have but only undisclosed data points would be able to help lead to better conclusions at this point. Best wishes.
HappyLibrarian,
All of us have different experience and understanding levels with regard to this company and its potential. With this in mind, I see the defensive posturing for potential failure of this investment in this last post of yours as more of a response to current circumstances than to the real potential of their products. Your risk reward comment by default really underscores the inability of investors at large to really understand the potential breakthrough the DCVax technology represents. I have talked to a number of doctors (some respected surgeons and radiologists) and nurses recently and they for the most part have no clue about why this technology might work. In their minds it is related to the failures of past immunotherapy attempts and at best a salvage clinical trial therapy. Wall Street is and will be the same way until one day they will wake up and realize that they need to change their bets. The few firms that have already recognized this potential have been busy over the last few years and those who sense the potential are watching, waiting and have cash on hand. Don't lose sight of the big picture. The disappointments in results from other therapies have created an even bigger demand for something that works. The market has priced in silence on interim analyses. A statement from NWBO indicating that a second interim has not been reached would cause a shock wave as all thrir products would need to be given some weight. Best wishes.
sentiment stocks,
I think regulators here need to make sure they are certain they have interpreted the newer laws correctly and fairly if they are to find any chance if possible to allow conditional approval during an ongoing followup period to determine and ascribe full benefit. Best wishes.
sentiment stocks,
You thinking it's a group trying to help get someone out of a mess or maybe just a lucky stalker that waited for the right time. The odds surely don't favor a lucky stalker if they haven't been in before this. Best wishes.
sentiment stocks,
And on that note, didn't the Germans decide to push for end to end automation kind of as a requirement? Where might those best minds in automated cellular manufacturing equipment be located and wouldn't the country with the cowinner of the Nobel prize related to dendritic cells be motivated to get er done? Hmmm. Best wishes.
sentiment stocks,
I like the part where it states "In addition, the need for certain high-cost materials is eliminated." Kind of like maybe a more controlled environment might have something to do with Pyrrhonian's pet peeve about maturation. Best wishes.
woodrow5,
Thanks for the input. Best wishes.
pgsd,
Good news is being balanced out by need for cash. Waiting for other positive news has been given almost no weight due to history of company. Net net this 1st arrow is a wash until further notice. Best wishes.
flipper44,
Well put. Best wishes.
maverick_1,
One of "about 7 arrows" has hit the target. Ein. Still a risk with a raise but I still really like September. Best wishes.
lattices,
I believe your thinking is correct but would also add that there are long term smaller investors that this may be aimed at as well. These supporters are more likely to help stick to Linda's plan if their shares should ever become a critical factor. Best wishes.
Rkmatters,
Gee, why would they have measured CXCR4 receptor numbers? Oh that's right, it's a highly conserved and specific receptor related to mobility for several types of cells as well as a hound dog receptor that moves DCs towards inflamatory signal zones. Now why might NWBO patents with regard to CXCR4 and their antibody research be important with regard to getting cancer cells to drop their guard at those inflamatory sites while potentially getting their competitors to do everything they can to stop them? Those hound dogs have been, and are being, bred and trained by NWBO very well just as you have duly noted Rkmatters. Best wishes.
flipper44,
Yes. They would at least need to know something held as "confidential" information. I also believe the Street knows that DCVax-L is at the endpoint of any historical grounds for failure. Even blinded results are currently or will soon turn the corner into unprecedented territory hence the final attack before others catch on. Best wishes.
Pyrrhonian,
Do you remember what your expected SOC PFS was in those predictions? I didn't see the posts much under that handle. Your more recent posts seemed to point to around August/September as the end of the road for the idea that no benefit can be expected. Best wishes.
Pyrrhonian,
As you have stated on multiple occasions, one of the main reasons maturation of DCs is needed is for mobility to carry antigens to the lymph zone. Low dose and multiple site dosing of DCs has been demonstrated to improve mobility as well. flipper44 shared a few slides a while back demonstrating the low dose effects. Individual DCs or subsets of DCs may also respond differently to compounds released by non self cellular degradation in an opposite way than they respond to general freeze thaw degradation of whole tumor lysate. As you noted, multiple freeze thaw cycles releases maturationally inhibitory signals so that those that do migrate are more likely to be highly screened participants do to some type of prostimulatory response which created sufficient maturation. This would correlate to the observation that only small numbers of DCs are actually needed to create a full blown immune response. This is also consistent with your observation that only a small number of key antigens might be buried in a tumor mass. We must never lose sight of the fact that selectivity is a key driver for a functional immune response because otherwise there would always be overwhelming interference from the natural cycle of self cell death and replenishment. Best wishes.
kabunushi,
100% agreed. Best wishes.
HappyLibrarian,
The external investigation is tied to the findings of the internal one. I believe as you do that the internal investigation is done and recommendations are being acted on. I do not believe they will release one without the other as there will be crossover information released. Best wishes.
Rkmatters,
Thanks for the followup. I definately lost track of the BSSR point made about the trial resizing and should have made a mental note to maintain the connection. NWBO will do anything to keep their options open and this is a positive and a negative. Investors have lost opportunity cost due to time but longer term this allows results to benefit from the added flexibility and learning on the go without stops and restarts which is even more costly. Investors who recognize this can use this to their advantage one way or the other. Best wishes.
Evaluate,
Yep! Now add in a little grapefruit juice and you have a winner. Best wishes.
maverick_1,
Thanks for the effort and sharing. Best wishes.
duderaja,
I think longs here have a pretty good view of the big picture. Investigators on the other hand are having a bit of trouble taking it all in. Like a gnat trying to swallow an elephant. Best wishes.
HappyLibrarian,
The heretofore absent conference call would appear to be best done with investigators and legal counsel on hand as questions arise. My guess is that it might include guest appearances from investigators as well as CEO Linda Powers, Dr. Bosch and perhaps one or 2 other key players. When the investigation is done is when I expect it. Best wishes.
Rkmatters,
I think I understand your point here. I may have missed something which I hope you will point out but just to be clear, adding patients while adding a country is still resizing the trial unless all of those patients were expected to enter into a separate WBC analysis. From my understanding this analysis was supposed to be done at the end of the trial and not impact enrollment. Even your example shows the 108 patients added from the original protocols appear to be divided into both the regular Phase 3 and your WBC check down group. Now one can argue the risks and benefits of extending the trial time in the hopes of finding financing sufficient to cover preparation for manufacturing capability on 2 continents vs perhaps getting quicker approval and manufacturing faster on one continent and then deal with the delayed readiness later. That is something they were certainly dealing with in late 2013 and early 2014. I'll read your post again but this is what I came away with after reading it about 1.5 times. Best wishes.
HappyLibrarian,
What has happened to investors over the last year sure looks and feels wrong. When investors express their concerns about this I feel it is generally a healthy response to the circumstances but I personally would want to see the big picture the way NWBO has seen it to make my own final judgment. I expect the investigations and an eventual conference call to go a long way towards bringing an adequate explanation. If that doesn't get it done then I'm sure a multitude of long drawn out court cases will. Best wishes.
HappyLibrarian,
I agree regulations need to be tighter with regard to management accountability to all shareholders. After seeing the pumping by the VICL CEO right before terrible results, when he had enrollment numbers that told the real story, and the failed legal action to hold him and VICL accountable, I realized that until the judiciary has a mandate, they will not act on behalf of investors. I see Linda as having that same protection but having very different motivations as do those who she has joined with in this effort. She has also come under personal attack by commentors which the CEO from VICL did not have to endure.
Sure we can judge the situation as we see it now which we see as looking into a mirror dimly" (an out of focus reflection) or we can stand behind our positions as we see fit and wait for 20/20 hindsight. Best wishes.
hopefulsurgonc,
I think you are on the right track with your thoughts about the pseudo trial results because they are more mature overall. Primary data completion is expected next month but this does not necessarily mean that OS has been established with that trial. Both trials are similar in one respect and that is that neither has enrolled the original number of patients expected. When lightning strikes the same person twice in the same place and there is no one dead there is something very unique happening. This is essentially what appears to be happening to NWBO here. Neither trial has been stopped for futility and neither trial has been stopped for success. The pseudo trial stopped short of full enrollment before the main trial stopped the new screening. If success was being expected more for the pseudo arm than for the main arm this would make perfect sense since earlier strong indicators would be coming from the pseudo trial and the additional pseudos expected to be found would have been enrolled into the Early Access Protocol as has been documented by others on this board. The pseudo trial might soon report PFS and OS or at least a trend or strong trend in OS without compromising the main Phase 3 trial because it was run independently from it. They could and would do this if they expect the final results will eventually be added in to the main trial results which may have, as most believe, already reached a milestone of some sort with regard to the DMC. If NWBO has reached a milestone in the Phase 3 but the company does not want to unblind until full PFS and OS is ascribed to the entire combined intent to treat cohort then this may be all we will get for now unless this is enough for other contingency news to be released as well. Should contingency news be released, it may be like about 7 arrows all pointed at the same target and destined to hit at about the same time or at least in fairly rapid succession. Best wishes.
Shane Chowdhury,
This is exactly the dichotomy that is creating the angst. If you want a better answer you need to speak to the kinds of psychologists that help do profiling for jury selection and the FBI. Best wishes.
2014turnaround,
I believe you are close to right but that there might be a little more dripping down because the need for cash until news will weigh. Those who may want to cover will work to reinforce this argument to keep the price down as they do and there is really nothing longs can do to counterbalance it. Rkmatters shares the voice of reason on this. Unlike Rkmatters, though, I don't think the trial needs to end for there to be good news. I do believe that at least a confidential threshold of sorts needs to be crossed and that this may have or is about to be crossed. I also believe that NWBO has discretionary moves available to them when this threshold is crossed which I believe they think is in September. Rkmatters thinks it might be in October but neither of us can be sure. Best wishes
HappyLibrarian,
Hey, I don't disagree but whatever strategy they decided to put in place seems to be what they are sticking to. No amount of challenge to that strategy seems to be having any effect and so we wait for it all to play out. The independent investigation will report on its own timeline, trial updates on their timelines and business progress when they are ready to share that which is probably when trial news is available. The UCLA videos were helpful but with litigation pinning them down, we do need to read between the lines to some extent. Linda has put herself in a tight spot to some extent with some of the public comments to investors that she has made and financing moves that did not provide sufficient funding between bites to help support share value. This will be used against her if there is any final negative outcome and she knows this. Best wishes.
iclight,
Correct. This is the point at which Linda puts herself in harms way legally to some extent if she does not shut down the spending big time because litigants would seek to build a case that she is trying to sabotage the company for her own future benefit somehow. Small raises now and especially since late last year have actually worked to speed up this process. If she knew a definate time frame was in the works ie September primary endpoint data collection or other more specific reason and purposely did not get funding for that entire period knowing that limited information would be released by company strategy, then fiduciary duty could be found lacking. This is another reason why I believe she will be proven out. It's all on the line. Best wishes.
chinatown1980,
I remember seeing it in one of the comments posted but can't remember if it was on Twitter, ihub or somewhere else. I didn't write it down because I didn't think I would be mentioning it in a post. I looked back on some of the ihub posts around the time of the article and have not found it in my initial search. There is a chance that I remembered wrong or misread something but I don't think so. I'll keep looking. In the mean time let's see what shakes out. I'm interested to see if I remembered wrong or his silence continues for a while now. Best wishes.
HappyLibrarian,
I guess Rocky just quit and the story ended. Funny. There is a price to be paid for not giving up. Sure Cognate might find a way to survive but they certainly can not thrive without NWBO. Their NWBO stock is worth the same price ours is and sure they have the equity from their build out but that could start disappearing quickly. They would be so wrapped up in litigation from disgruntled investors that making a 5 mile long spool of tangled monofilament fishing line covered in pine pitch and mouse trap glue good again using only your bare hands would be easier. Then add to that the overhead costs of maintaining their manufacturing facilities while they are busy in court and trying to run a business sullied by default and things wouldn't be much fun at all. They do have a well known big investor who might not be too happy right? Best wishes.