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flipper44 and Senti,
Notice that Dr. Prins does not even mention the better responses seen when chemo is used to up regulate methylation in some non responders that Dr. Linda Liau mentioned in her video. When you combine all of these synergistic effects wow! These methods must now be encouraged to become standard practice while we await formal validation. I think the regulators have known this for a while now and I believe their demand for a crossover was serendipitous for cancer patients.
Ready4bluesky,
Have you considered the timeline of Mr. Woodford's selling of his AZN stake with Dr. Prins mention of a partnership deal with BMY and MERCK? If the negotiations with BMY and MERCK were with all 4 parties but final agreements are principally between UCLA and said parties then a formal announcement by UCLA may be necessary for NWBO to announce anything. Dr. Prins may be acting in the interest of NWBO investors without having UCLA make a formal finalized announcement until all parties are agreed upon the timing of such an announcement. If Mr. Woodford's intentions are still in doubt and or there is other news expected soon, the formal announcement might be timed to coincide with that other news. Mr. Woodford's cash in hand may also be pointing to this.
iclight,
That is really strange. When I went to that site there was no image at the top as a header like I saw before with the picture you and flipper44 mentioned only a credit.
Stillwell888,
I believe you are on the right track with your thought process. DCVax-L requires tumor lysate so L as it exists now may not be suitable for a vaccine such as the one you suggested, however, a partially allogenic (created outside of self vaccine) based on cultured T-cells harvested after DCVax-L treatment might be cloned and banked as a way to begin the process of creating an allogenic activated T-cell/DC primed vaccine that targets all critcal targets found in any given patient and will also have the capacity to hunt down mutated neo antigens.
Shorty on the move. Someone who hasn't been wrong in 2 years appears to have made a quick U turn. Who is selling their shares today? I guess someone had to sell the pearl of great price so that some one else could buy it. Maybe its time to set those high ask prices folks. Official validation from big pharma means there is a new base support price in the works generally at $5 and higher. FDA validation puts it well... from a failure price to a new technology platform leader price. Should that day occur soon, longs and cancer patients will lift their glass filled with grapefruit juice to celebrate a great victory. In one hand the victory toast in the other some very, very burnt toast to be piled high as a monument to the one who gave us the supreme placebo toast to remember hubris and distortedly disingenuous prose by.
sentiment stocks,
I also said last year that L would probably be partnered but not Direct yet because Direct had not been tested at optimal dosing amount or spacing which is needed to control immunosuppressive macrophages which are recruited by cancer. I have stated my belief numerous times on SA that Direct can control a subset of macrophages (M2) that are immunosupressive. I pounded on this with Pyrrhonian and he finally conceded that there might be some hope for this to happen. I did not show him my proof because I generally won't do that unless someone wants to show me and everyone else that they do not know what they are talking about and or are deliberately trying to mislead and refuse to concede a point they have no proof to contest. I also wanted the researchers who have spent so much time working on this to give their presentations on their timeline. Besides, I like to use a hammer only when it's needed because time by itself often brings the truth home.
While I am here senti, was there a direct reference to DCVax-L with regard to the talks about colaboration or could this just be a colaboration agreement with UCLA?
I ask because I don't recall hearing NWBO mentioned and I had heard or read something about a colaboration with UCLA and someone earlier this year. Best wishes.
Cherry Tree1,
One blessed word says it all....
SYNERGY
flipper44,
You are correct. Dr. Prins also mentioned using monoclonal antibodies " like" anti PD-1 in conjunction with DC therapy to eliminate tumors. Now if the tumor microenvironment causes DCs to revert to circulatory DCs that move away from the tumor environment in less than 2 weeks, how often do you need to inject new DCs to keep cytokine control of macrophage subset M2 from causing immunosuppression while tumor load is still present? This is why I lamented about Direct injection spacing in Phase 1 on Seeking Alpha. The conservative nature of the spacing kept results deliberately suboptimal with a treatment (DCs) that has a strong safety history. Some have even categorized it as a placebo. I am looking forward to what this "grapefruit juice" that can control immunosuppressive macrophages can do in Phase 2.
flipper44,
Lots of good clues about Direct hidden in this presentation as well.
iclight,
Where is Dan Kitwood's photograph that the credit is supposed to be for? I mean right at the top there is the caption for it titled Within sight then the credit but no picture. What happened to the picture that the credit is for?
austinmediainc,
Manipulation of stock price happens all the time as we have seen here. Whether or not it is illegal and prosecuted or in the best interest of the share holders is quite another thing and remains to be seen once some time has passed for good analysis. What also remains to be seen is whether Linda really had any other choices for funding or not. Once Mr. Woodford placed himself in a wait and see position with regard to the investigations, funding choices obviously became limited. With his own ongoing investigation taking place everything kind of hinges on what each party says and whether or not they make a joint statement.
austinmediainc,
I know the changes, missed timelines and apparently misleading statements you make referrence to seem personal here because we are invested but NBS was touted and VICL looked good from what investors wanted to see from management. They did updates and they did conference calls yet they still collapsed. With VICL, the CEO kept giving encouraging talks right up to the point of failure. He had the enrollment picture but did not share it though it painted a clear picture of failure well in advance. Still the courts sided with VICL. We have the advantage of knowing what we are dealing with. Adam and others have been warning for a long time about the risks so we really all should have been well aware of them for quite some time. I know I have. Best wishes.
austinmediainc,
I appreciate your concern but the science I have written about and hinted at is well past the theoretical stage. There is documented evidence from non NWBO preclinical trials that a lesser (incomplete) form of what I believe NWBO is trying to accomplish with Direct actually works to some very visible extent. NWBO is working to achieve immune memory and this takes more to accomplish than what the preclinical trials from these others I looked at have proven can happen. For obvious reasons I do not want to get into all the details but like I said, for those willing to dig and put 2 and 2 together, there is no small amount of comfort to be found. Knowing your risk/time/cash need tolerance and staying within it during any given investment period is still better comfort. Best wishes.
flipper44,
Hear, hear. Mesenchymal form utilizes the CXCR4/CXCL12 relationship for mobility and apparent site selectivity for relocation.
hopefulsurgonc,
Thank you for posting these thoughts about CXCR4 and thanks flipper44 for your post as well. There are plenty of positive things we all can focus on and this type of information will be helpful to many the way you are presenting it.
CherryTree1,
In my opinion, the share price is where it is at now because NWBO felt (feels) the need to ward off any potential hostile threat from Mr. Woodford. This is done by way of dilution and silence. I believe Mr. Woodford has learned a costly and valuable lesson about playing hardball with Linda in full public view. Perhaps now they are back on the same page for the most part but Linda will not take any chances that this is not the case. Crickets until regulators speak is the modus operandi.
Turtle65,
I noticed that the ClinicalTrials.gov site for L Phase 3 says at the very bottom that the record was processed on 3-31-2016. I don't recall seeing notes like this before without an update with it. Maybe you or someone else can comment on this. Best wishes.
Turtle65,
Some plant, others water (some remove weeds) but someone else takes care of the growth. While we wait for news, why not whistle why we work. By the way, Evaluate dug up some info on CXCR4 a while back and there is a whole lot more to find. We are past the time to accept the fact that they won't be saying anything until the regulators do. If you had kids you would know all about "Are we there yet?" and why asking that question doesn't get us there any sooner. Best wishes.
mapman1010,
Do you think we might be range bound for a while due to the election cycle or do you think biotech news in the next 3 months will be sufficient to carry the day through the summer months leading up to the election? Valeant might weigh? Just trying to get a handle on what I see happening and to me a quick rebound seems less likely than a normal cycle would create. Best wishes.
Doktornolittle,
My hope with their automated manufacturing process is that they have designed built in flexibility to add additional stages. There are very good long term reasons for doing this so I assume this to be the case.
As you mentioned, approvals are indeed different than having the process completed. Any additional stages added would need to be approved separately but perhaps with an expedited review. Best wishes.
Ready4bluesky,
When you concern yourself with what investors bought into 15 years ago and try to compare that with the risk associated with the same company that Larry Smith 1st recommended in 2012 and I invested in shortly before his recommendation, you are not demonstrating a balanced perspective.
Almost any startup biotech is inherently a very high risk for long term success. That is why there is so much volatility associated with them. Traders move in and out with the various cycles at play until the binary events are expected. Surely you understand this. You also understand that trial changes and delays are part of the landscape. Trial design combined with clinicaltrials.gov listed timelines are the only guidelines investors should ever give any credence to as all other possibilities are generally just wild guesses, some more educated than others. I have mentioned more than once that 20 years from business start to some type of validation was the timeline I have used for looking for my original entry point. The idea, of course, is to buy in before others have more fully caught on at the double dip. I bought right and could have made much more money by selling near the high when the technicals indicated a reversal was possible but my time and target goals still had and have flexibility enough to see the investment through.
If the goal is to buy low and sell high you must give your investment enough time to reach your target. If the time is too short or the target too high you will never have the chance to achieve that goal. This seems simple enough but setting realistic goals based on timelines guided by what I mentioned above seems to be where many investors go wrong. Becoming disgruntled is easy but changing investment behavior to a very disciplined approach is much more challenging. I hope your ARGS works out for you as at least the 1 in 10 winner Larry Smith's strategy suggested is necessary to break even with the speculative portion of your balanced portfolio. Best wishes.
austinmediainc,
Quote:
You can revert back to "I believe in the science" bs all you want but the truth is the company would need to answer questions about the info they have released for anyone to really objectively make any conclusion on the science or data.
-austinmediainc-
I respectfully disagree with you on this. If you would spend the time and got on the right track I can assure you that you can come to an objective conclusion about the science without NWBO commenting on it. The research path I followed led me to predict an incomplete response from Direct due to suboptimal spacing and perhaps duration of the injections. The MO including necrosis is also consistent with the research I looked into.
If you would spend more time looking into CXCR4 and how it relates to NWBO and multiple cellular processes, I think you will find that you will be rewarded with a much reduced stress level unless, like me,your wife is not yet satisfied with the kitchen remodeling project yet.€:j)
Ready4bluesky,
I know this may seem strange to you but do you remember the "grapefruit juice" comment by Adam? That was in response to a post by me over on Seeking Alpha. The reason I mention this is that I had postulated that NWBO might be pushing Direct to the forefront while the public focus stayed on L. If this is true, then all the manufacturing capacity needs to be ready for Direct as much and probably more than for L. If they are tweaking the automated manufacturing process for Direct to improve the concentration of DC subset cells associated with survival, then you would certainly want to go to the finish line with L to buy time unless the regulators stop the L trial early for some reason. The current delay could be for many reasons but manufacturing processes for something that may be expected to have a seriously high demand would certainly be an issue with the regulators.
The PIM approval process requires proof of ability to manufacture at commercial quantities (scalability) be given. Getting through the hurdles takes time and a great deal of money. Those who have their eyes on the manufacturing sites and job positions being filled probably have the best picture of what is going on with NWBO right now from a retail investor perspective.
Some on this message board have speculated that the news about Direct will not be extremely encouraging and that is why NWBO is witholding it. I think the opposite is true and that Mr. Woodford knows about this and the reason for the L screening hold as well. I believe the paper being worked on with regard to Direct and planned for publication in a peer reviewed professional journal will have data and observations that could significantly change the investment climate surrounding NWBO right now. I also believe that the screening hold lines up well with trial patient and long term investor interests one way or another.
Stillwell888,
Good observation but is anyone able to see if shorts that might need to cover used this restructuring time to mask their moves. I am not sure there is any accurate real time clues to check this. Maybe TC knows. Best wishes.
Sojourner55,
Well stated. Steady as she goes and in the mean time find a way to bless others. Best wishes.
john1045,
Mr. Woodford has cash in hand and probably a buy order planned for a date that he will hear about first. News that can be held is being held for a significant punch. Linda said she would take the trial to the end. Only regulators can change that plan. Best wishes.
austinmediainc,
First off I hope we all do well and do not fault you for feeling as you do. The silence certainly is deafening and I would like more transparency as well. I just don't need to vent. There will be plenty of those who will vent through attempted legal action should this company fail to live up to the promise of its science and public comments.
The timing of the "what ifs" you mention are not the basis for my investment. I am patient to a fault which is why I didn't invest until I saw an opportunity that provided a reasonable timeline for trial completion including additional time for resizing and usage of the extra powering reserved by design. I did expect Direct to move along a little more quickly but now I think they have a good enough understanding of what they have and the manufacturing wherewithal to make the final production changes to use the next Phase to finish it up.
austinmediainc,
The dilution you mentioned is why I waited until 2012 to invest at near the then all time lows. I have started to accumulate under $2.00 again but have some reserved for under $1.00 if the regulator decision or Direct news drags on much longer.
One question all investors ought to ask themselves is whether or not the general market will find price support anytime soon with baby boomers ready to start cashing out and China trying to reorganize it's economy. If the IBB is dropping to make room for newer technology not owned by the big bios that it is primarily made up from, what does that say about Mr. Woodford's strategy? Seems to me he understands what is happening and is preparing for 3-5 years down the road. When are manufacturing approvals for Direct expected?
TC Trader,
The manufacturing ramp up is one of the keys to approval for both L and Direct in my opinion. Direct may also be in the process of being improved upon even more. I believe NWBO may be working to achieve higher concentrations of a DC subset in Direct that is associated with better patient outcomes. This would also need to fit into the fully automated process they are working on. The delay of Phase 2 may be the price paid for the next trial to be shorter and the last one they need to run before potential approval.
sharpie510,
Some of my earlier research pointed towards the levels of certain growth factors that act as scouts in the body might be a determining factor in whether a genetic mutation is recognized early enough to prevent precancerous cells from becoming actively growing cancer or not. DCVax-Direct, I believe, attempts to reverse a central part of the masking and signaling process that develops once pre cancer becomes active cancer. That DCVax-Direct vial shows us that some folks understand this.
austinmediainc,
I think most longs here are go big or go home thinkers. If you have a balanced investment approach then you just wait for the science to be validated or not. As much as we would all like more clarity, our dissatisfaction with the current state of affairs will not change anything. I see no positive contribution in terms of discussion from a public complaint by me, especially when I had predicted this sort of price action scenario was possible quite a while ago.
The current price reflects dissatisfaction with management, need for ongoing funding, extended time for temporary hold, general trend in the IBB and lack of good available funding options for smaller biotechs. On the other hand, suppose Mr. Woodford rejoins the effort, the temporary hold is lifted and Direct Phase 1 has patients that are still alive and doing well. Or what if Direct has fully automated manufacturing completed or nearly complete and approval process for manufacturing underway. Maybe the DC subset that correlates to survival is being more highly concentrated with a new stage in the manufacturing process. Lots of things can happen during quiet periods and not all of them are necessarily bad even though the price can not reflect what we can not see.
Ready4bluesky,
I think the main risk here is wondering what FDA will say about the data or any requests made before data submission. Linda said they were in ongoing discussions with FDA and the crossover complicated OS readouts so.. once the data was submitted there was a new risk to acknowledge. Data was submitted in October apparently so the report needed to disclose any new known risk since the previous report. This risk includes regulator decision making based on complicated OS results which are now awaiting statistically significant separation and quantity to occur. This would reflect the early vs late treatment comment Dr. Linda Liau made.
Sub Atomic master,
You bet sorting all this data out is hard and time consuming. They must do it because OS is unlike anything they have ever seen before in GBM. The blinded trial might be having trouble ending early by relying on PFS alone or the trial was unblinded and they are seeking approval so they are waiting on OS events which is complicated from FDA mandated crossover delaying OS events ("..doesn't really help our trial..." Dr. Linda Liau). This will complicate the approval process as per Flipper's comments.
Quote:
His "tripping factor" comment is saying IF the entire trial is marginal, and the mesenchymal subset is strong, they might approve the subset. I have seen a case of this (forget who), so have to agree with him there. But it would not be normal for the FDA to do this. - exwannabe-
You are correct but FDA needs something that works for GBM and the OS appears to be greater than 24 months here as per Dr. Linda Liau's comments in her October presentation. Her OS referrence points for survival were from newer data indicating 24 months OS possible. Accordingly, this DCVax-L protocol is benefitting patients with OS beyond this mark as per her comment about all patients apparently living longer. Besides the stronger mesenchymal results, Dr. Liau mentioned how even some proneural patients can benefit at crossover by using the right kind of chemo. I am sure doctors at all clinical trial sites were made aware of her findings.
The questions surrounding the length of time taken so far with the screening suspension and the investigation has created shaky ground for investors due to time=money losses. Linda did say she intended for the trial to go to the end, perhaps in anticipation of needing to have more mature OS data. Regulators appear to be dealing with a good deal of information, some of which may be being reviewed in an ongoing process. I would think that a co-primary OS petition would not take this long but other reviews could take up to about 9 months. Multiple reasons for this delay seem to be reasonable. Though accounted for otherwise in disclaimers, there is every reason to believe this trial will finish enrollment and then finish on or near on schedule. Safety does not seem to be a cause of concern so finishing should not be an issue. This as a minimum brings HE revenue.
vator,
One of my posts was deleted and then restored evidently because the first moderator did not recognize the correlation between CXCR4 and NWBO. It was apparently restored because another moderator made the connection. The lesson to be learned for me is that the dots need to be connected fairly closely here or someone might misunderstand. Best wishes.
For those looking for something to do while we wait for news on L, what correlation might method A vs method B have from the Phase 1 Direct trial? Feel free to share supporting evidence for your thoughts.
Ready4bluesky,
Your handle says it all. I think we are all ready. My hint does constitute a part of the risk/reward÷time ratio so I will take up your query.
Biotech investing generally is best suited for traders that work the shorter term cycles. Those who do invest in this sector absolutely need to be honest with themselves about risk over time tolerance. If this is what you want me to agree with you about I do. What I don't agree about is the need to avoid the risk and potential reward involved with any small cap entirely just because a company has an unsettling management style or strategy. As for those who have held for a while, last year was a good year to mitigate risk near the high. For those who have held like me, we still see reason to wait and one of those reasons is all about CXCR4.
For now, NWBO is priced almost at failure valuation for L as the current situation they face with an ongoing investigation and regulator review of data necessitates restraint by Mr. Woodford and others. Retail has now had the opportunity to purchase at nearly 90% off the 52 week high. Failure of DCVax-L would take the price under $1 for a while anyway but this Phase 3 does not look like it will be a total failure. In all likelihood the trial will be allowed to finish enrollment as a minimum and HE reimbursement would follow. What is going on now with regulators seems to be separate from the opportunity with HE. In the mean time we might want to look at clues as to why Mr. Woodford likes the science. Care to share what you know about the importance of CXCR4?
Time for another hint as to why CXCR4 is an important target. In adults macrophages generally exhibit a primary function of consuming or phagocytizing their targets. In prenatal to neonatal situations macrophages are principally involved in the process of creating new vascular pathways to support growth. Many types of cancer are able to signal at least some macrophages to revert back to their original function to support cancer growth with new vasculature. When this function of cancer cell signaling is interupted, new vascularization in cancer can be interupted. Guess what important and basically non alternative pathway many cancers use for this signaling to macrophages.
exwannabe,
When I referred to the idea of "stand alone" in my previous post that was not meant to imply comparison to historical norms. This concept is based on evidence derived from other clinical trials that point to this potential with DC therapy but for the most part has been negatively impacted by slightly to moderately active "placebos", too broad of a target population and definately the pseudo effect. FDA is tied to this trial by their own insistance for a cross-over which appears to have been a blessing to those who are "living longer". Now FDA must do everything in their power to learn what the implications of this mandated cross-over means. I believe they want to verify the biomarker ties to longevity, verify a solution to the pseudo problem, want to understand potential synergy better and understand MO of DC therapy on various subtypes. I believe they are doing that right now.
Some here seem to think that FDA is so legalistic that they could care less about what is at stake for patients outside of this trial even though the trial will help them learn a great deal about the science. These folks believe this trial will ultimately fail to gain approval because of trial design flaws. I believe there is enough flexibility designed into the trial and motivation from regulators and research community now to see this through to the end. That means we will at least get to HE reimbursement as a minimum (trial fully enrolled) or better. This minimum would mean another trial but with income. Better could be up to much, much better and perhaps be more in line with the production capacity ramp up we are seeing.
Koman,
Quote:
So there is every reason for the regulators to tell NWBO to just design another p3 trial with OS as the primary endpoint and no cross-over if there was any hint of OS difference in this current p3 trial. Don't blame the regulators for doing their job.
-koman-
Well yes but.. the crossover was mandated due to an invasive procedure for the placebo and active treatments. The need to retain patients for assessment of secondary endpoints (with a change to OS co-primary in mind perhaps from the .03 alpha spend reserved) necessitated the cross-over as well.
This treatment may be showing efficacy signals on multiple levels. It may show stand alone efficacy with mesenchymal GBM genotype with regard to PFS and OS, stand alone efficacy in mesenchymal phenotype at crossover in OS and potentiation/repotentiation of checkpoint inhibitors and various chemo/radiation therapies with PFS and OS. With this kind of activity possibly going on, FDA will want to figure this all out especially with the biomarker correlations to survival in hand. The data from this trial is just too valuable given that patients are living longer than a 24 month median. Living longer is the gold standard right?