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austinmediainc,
What you wrote is absolutely correct but judicial interpretation allows so much slack as to make the definition virtually useless unless being used selectively to make an example of someone. I believe the recent court decision in favor of VICL and it's management vs shareholders made this perfectly clear. The laws as they exist now are essentially "buyer beware".
I followed a court case fairly closely a while back that had to do with eminent domain. A beachfront property that had been passed down within one family for many generations was basically handed over to local authorities for development just to increase the tax base. That is the way the courts work sometimes. Linda knows the laws and if NWBO finds success, most lawsuits against NWBO, if not all, will most likely fail. All these arguments about what Linda has or has not done reminds me of the movie "The Producers". The movie was supposed to fail so the money raised for the production would never need to be paid back. The only problem was that it was so rediculous that it became a huge success and created a whole new set of problems. Any naked shorts and or scheming CEO would have similar problems right now. The CEO here has had multiple chances to be vetted and still has the same accountants. Naked shorters, on the other hand, have had their wrists slapped recently. Best wishes.
iclight,
The strategy here appears to be to benefit the private investors first as they laid out the cash in the first place in a very risky investment. They almost were roasted themselves as Linda took loans from friends to keep things going at one point. The risk they took was real and it has paid off but not nearly as much as it could from success with DCVax. Their derisking diluted retail stock holders, and perhaps still does, but also held together the supporting network of companies. This network was designed to get DCVax to the finish line without the absolute need for outside help. In the mean time, the science became more compelling which brought in Mr. Woodford. This allowed NWBO to take the brakes off of ramp up. Prior to his interest Linda got NWBO listed on the NASDAQ and then on to index funds. These are accomplishments that many penny stocks never achieve. Now we wait patiently or choose to bring up every little thing that the company has done to stay in business over the years. These are things you look at before you invest and Phase 5 showed us many of the pertinent filings. For those who were inclined to make the proper due diligence effort, most of what they wrote was not new.
As to my best wishes adendum, this was not directed specifically at anyone, especially not you, even though the post was to you. This was just my poor attempt, from a quick thought that crossed my mind, to remind all of us to stay patient focused. If patients are doing well with any treatment then those invested in companies that make those treatments will have a chance to do well with their investments. Best wishes (no adendum and sincerely meant).
Rkmatters,
You are correct. Bases are covered but FDA has made no formal decision. This means that discussion of this matter may come up during FDA consideration of DCVax under certain circumstances. Under other circumstances the discussion would be a mute point if you catch my drift. I expect this issue to be a mute point.
iclight,
Good post! This clearly demonstrates the financial hardship that NWBO was in before Linda took the helm. This arrangement is kind of like getting free warrants on top of lower priced shares for financing right? Great cash flow strategy to minimize risk for financiers and spread out risk to other interested investors while the company gets back on its feet. Thank you for showing us all how creative Linda and Toucan have been to keep this company alive. Very resourceful people at NWBO. Those who don't think so should just wait and complain all the way to the bank or their favorite lawyer, whichever comes first. Best wishes, betting against cancer patients excluded ie. no safety issue here.
autologousvax95,
Awesome news! This is what many longs here have been hoping our investment would lead to on a wide scale. If patients do well our investment has a chance to do the same. Best wishes to you and your friend.
flipper44,
Freudian slip?=LOL=SYNERGY=GO NORTHWEST BIO=Turtle dance=Smiles for the board
foxhound02,
I warned on my Seeking Alpha posts more than 2 years ago to watch for DNDN type of manipulation. When Larry Smith was attacked I warned that character assassination was another ploy used and to expect lawsuits, hostile takeover attempts through potential board of director additions and or outright all out scorched earth attack on share price to wrest control out of Linda's hands. Sound familiar. Linda already had the patents protected, the antidilution clauses came in after I was already invested. I had hoped that Linda and Mr. Woodford were on the same page but it appears that was not the case. Mr. Woodford, whether "duped" or not, must take full responsibility for actions he took that caused damage to his shareholders investment. That is what good investment managers do.
The Direct Phase 1 trial did not reveal a complete MO so that the trial could morph quickly into Phase 2. This was most likely due to inadequate spacing of treatments more than anything, in my opinion, though number of tumors injected also plays a critical part in systemic immune response build up based on prior mouse model evidence.
Much has happened in the last 2 years with regard to DCVax-L and Dr. Linda Liau has allowed us to see a glimpse of that which puts the focus on OS and finishing the trial. Any action taken earlier than that would probably require an unscheduled look by regulators or petition for early regular approval which would be risky based on what NWBO has said they were planning to do. They have said they will let the data mature and finish the trial as scheduled. The potential then for an unscheduled look or data request by any of the regulators and or potential looks at other trial evidence from a parallel trial and more mature open label data could explain what is happening.
flipper44,
My understanding is that those thresholds appear to be the result of specific monocyte to DC maturation process. DCs act as scouts, sentries and messengers as well as generals. Various environmental factors, growth factors and inflammation signals cause specific types of maturation of monocyte precursors and DC response. Signaling interference can prevent a completely controlled DC response which is why the specific parameters you lsited are required for the observed response. Certain types of DCs are better at controlling this interferrence. Sorry but don't want to get too specific here. There are people who have spent lifetimes working on this and they deserve to have the light shine on their work when they are ready to present it.
flipper44,
You are correct. Manufactured confusion by any other name is still manufactured obfuscation lol.
flipper44,
Remember one of the Direct findings was survival benefit related to a certain subset of DCs. What do Linda's other businesses work with? One works with stem cells right? Interesting to note that at one point I found references to stem cells on the FDA IND#10206 site. That is not there now. Is this something else CLDX learned from NWBO or did they develop this on their own? Time will tell.
AVII77,
With regard to Optune, patient acceptance and quality of life considerations seem to be holding up its relevance to SOC. It seems to be an option but not necessarily an option that should be considered SOC, at least at this point, as many patients would perhaps opt out. This would seem to be a consideration FDA would weigh carefully with regard to possible alternate treatments with equal comparative benefit and better quality of life with regard to SOC as it currently exists. I'm pretty sure this would come up in their discussions don't you think?
flipper44,
My lol was for the answers found in your questions. I didn't explain myself with the response I gave to your test post. Best wishes, eh.
Quote:
No. Even what are considered fully mature dendritic cells actually still have the capacity to cross the blood brain barrier and uptake new antigens. Moreover, by simply increasing the frequency again, those critical DC expressed antigens in short supply get a second bite at the apple--whereas some may have struck out the first time due to attrition and batting average.
Correct and if chemo is concurrently used to promote lymphopenia to selectively retard Tregs in relationship to CD4 and CD8 build up.. badaboom badabang. Patients living longer.
AWESOME DUDE! (CA style response for the San Francisco treat)
All your answers are correct lol.
AVII77,
Very good post explaining the breakdown. A 10% dilution does not logically coincide with a 50% loss in price since that time, however. Any investor that ever thought Linda would allow a controlling interest in this company to fall into anyone else's hands without using every option available to her to prevent this does not understand Linda. I have mentioned this forced dilution clause on another site and your mention here is a good reminder. In my opinion, Linda would shut everything down to get DCVax to the finish line on her terms and that is one reason why I decided to stay invested until that time. That is a calculated risk on my part and I have some dry powder set aside for a scorched earth possibilty. Many have underestimated Linda's abilities and tenacity but but my analysis of her actions has led me to believe that she intends to reward those who have supported her efforts long term. I accepted the risk involved from before I first invested in this as an OTC company. Best wishes.
Pyrrhonian,
Correct me if I am wrong here but this study that you responded to koman about shows that later psPD appears to respond to TMZ better and these are being placed into the main trial. This is the opposite of what I thought I remembered was happening but then a light bulb went on or I just got sucker punched lol.
Early progressers are being removed either by actual determination or by indeterminate status and they do not respond well to TMZ. Some of the early psPD patients are being removed by way of psPD or indeterminate determinations as well and are also lower end responders of their group to TMZ. You and AVII appear to be arguing that this DCVax-L trial has been cherry picked to prove that extended use of TMZ will prove beneficial for a majority of patients and I agree. I also think that studies showing synergy between DC vaccines and TMZ indicate that treatment arm DCVax-L patients will have at least a 2 month OS benefit over SOC by the end of this study because of earlier acting synergy on lower tumor burdon. What say you?
By the way, the respect is mutual. I'm a truth miner. There is always more rock and dust than gold so you just need to keep digging. "He who seeks the truth with all his heart will find it." Best wishes.
koman,
I was hoping someone else could confirm my recollection about early psPD vs. late but if not I'll do some digging through my notes to see where I recall that from. As to the later psPDs being misclassified and placed into the main trial, I think a determination was made to aim treatment at those who fell into an expected range of PFS and OS to increase confidence level by reducing variance. Classification being less important for SOC vs. treatment than expected PFS or OS. Hope this makes sense.
koman,
If I recall correctly, there is a statistically significant correlation to OS based on whether there is early psPD or later psPD. This may be the rational for earlier screening vs. standard procedure as the Phase 3 trial focuses on eliminating the outliers. This may also explain why there was only one psPD found in the expanded access trial. Best wishes.
Pyrrhonian,
From a layman's perspective this reasoning would appear to be correct but doesn't this essentially cast doubt on the 3 expert radiologist panel that adjudicate these images? Haven't the images become more reliably interpreted by advances with image guidance and staining. Perhaps the 12 weeks needed in the past has been improved upon so that these experts are willing to attach their names to the readouts. I don't think they want to be known as quacks. I certainly would not jeopardize a well paid career for a single study for a no name biotech. Best wishes.
Rkmatters,
TMZ was approved based on a 2 month demonstrated OS benefit. No more benefit than this will be ascribed to it with regard to this DCVax trial since no other blinded trial proves there is more. SOC encorporates this benefit which is why any additional benefit is ascribed to L. This is why any synergy is low hanging fruit just waiting to be picked. DCVax is positioned very well to take advantage of a possible synergistic advantage in the measurement of OS and this is the reason why you decided to test the waters again right?
Rkmatters,
That study compared apples to hybrid apple/pears. The age groups were different and individual patient characteristics not revealed. How many besides the 2 month survivor didn't survive for even the 6 months of standard Stupp? The one outlier from a total patient group this size fell into the extended TMZ group. Good trend but this is why FDA requires blinded clinical trials for proof. Does this argument sound familiar? Glad you are smiling.
Rkmatters,
TMZ benefit is essentially low hanging fruit for DCVax to benefit from. Your concern about its use confounding the data is basically a non issue since no clinical trial was done to prove that potential benefit was as a result of its continued use. Your quote explains the undefined reasons why. DCVax protocol indicates that all benefit from additional therapies will be credited to DCVax with regard to OS outcome. So come on RK, it's OK to smile once in a while here.
Finding the Truth,
Educated T-cells work well in blood cancers. NVS and U PENN have a colaboration working on similar effect. The ultimate outcome of this news, in my opinion, might be a combination of DC and activated/engineered T-cells to keep the immune system in check and provide even longer term immune memory with memory B-cells involved. The trial you referrence and others have led to premature deaths from immune response. For now, educated DC therapy offers the safest way to regulate immune responses. Dr. Linda Liau has already hinted at this type of combination potential with the UCLA T-cell clinical trial for GBM they are looking at.
Remember when I wrote that the price of NWBO had hit bottom in anticipation of a new news cycle? Today marks the beginning of that cycle.
Rkmatters,
I am and have been extremely glad that this trial has a crossover option. While this is somewhat confounding, the reality is that FDA has the accepted monotherapy values for impact from previously approved therapies and those are the ones most likely to be used in conjunction with crossover. They will use these values to separate their potential added benefit from the total benefit observed. This is the way doctors and scientists operare. Dr. Linda Liau mentioned 2 chemotherapies and potential with checkpoint inhibitors that will show or most likely show synergy with DCVax-L and the chemo is relatively cheap and would be covered by insurance. This trial will measure synergies based on Stupp protocols during treatment and pretreatment and non Stupp, potentially optimized treatment, at crossover. This includes the potential use of check point inhibitors in combination without the full cost of a trial. I wonder if a company or 2 might be offering their checkpoint inhibitors to these patients for free. Win, win, win. This gives all patients a chance to benefit from the advances in research with regard to synergy and a look at what SOC may end up being later on. The flexibility at crossover is awesome. FDA has good reason to take their time with this and I understand AVII's concern with regard to stringent standards but this is where the flexibility that they have recently been granted will help if needed. Best wishes.
Sub Atomic master,
Angst does not even begin to describe what you have been through. No matter the names you have been called I admire your tenacity to stick with this company with the hope that they are truly on to something. My due diligence leads me to believe that they are. Steven and Adam do not want to disuss the absolute importance of injection schedule, amount of cells, number of tumors treated, duration of treatment, DC subset related to survival and the well established fact that DC treatment is synergistic with not only with checkpoint inhibitors but also various types of chemo and radiation. NWBO is on the right track. The only question is how many laps they will be made to run before they are accepted as proven. Safe effective synergy is king. RK figured that one out and I have had enough experience with it to recognize it when I see evidence of it. Remember, Dr. Linda Liau had 2 points of referrence in her video, the trial expectatations and 24 months OS now expected. In this context she stated all patients are living longer. Best wishes.
"Adam",
I see your journalistic prowess has taken a back seat to your enthusiasm.
Quote:
That's the most damning evidence against NWBO. If the company's technology was credible, there'd be a long list of investors owning the stock. Instead, there's just Neil Woodford, and even he's now come to the realization that NWBO was a mistake.
That first sentence belonged at the end of the previous paragraph. By the way, why did you use Steven's verbatim response to me on Seeking Alpha when answering another poster's question here on ihub around the time you first showed up on this board? Kind of interesting to me how the 2 of you seem so much alike at times with your responses here and you don't even say your response was a quote from Steven. Isn't that plagerism?
Now as to the points you presume to make in the quote above, what PROOF do you have that Neil Woodford has stated publicly or privately that his investment in NWBO was "a mistake"? The share price drop during regulatory review of data that keeps the company quiet is not proof of anything so don't try to use that as proof. Mr Woodford has said that it is too early to pass judgment on the company so unless you can show me where he has said differently you are putting words in his mouth that he has not spoken. Where is that journalistic integrity you sought to invoke upon yourself?
That long list of actively managed institutional investors that you are talking about is waiting for regulator validation to put the price over $5 and keep it there but then you already knew that or should have right?
One more tidbit for you to think about. Synergy is music to the ears of scientists and FDA is listening to a symphony.
flipper44,
I followed the Vical Allovectin-7 saga fairly closely, near the end especially. Their Phase 2 data was not nearly as compelling as what is available now with DCVax-L from all sources. Sad to see that the CEO at Vical got a free pass for "his interpretation" of the facts to shareholders. I followed his comments very closely and he knew the enrollment numbers which was critical info for investors but did not release that to them. Some of the last remarks he made prior to announced failure would be described by most as upbeat and encouraging. The courts decided to let this slide in essence saying buyer beware. Those who really believe Linda would do the same thing because she could are probably long gone but if not AVII has warned them even though the obscurred comparison to NWBO numbers from data is faulty.
I did not invest in VICL because data was not strong enough and consensus from oncologist commentors was imminent failure. My confidence level based on my personal understanding of the science was also too low to even take a small position. I only chose to follow it because it was immunotherapy based.
VICL is a poor comparison for AVII to use but if the message to us all is "NWBO is not a slam dunk so check down on emotional investing and setting short term time lines" then I am in agreement with that.
edwick709,
I will be glad to read through your suggested material. Good to have doctors and professors on board here and your contributions are much appreciated. I have no such credentials but strong interest has kept me glued to oncology related research. Historical cycles tell me we are nearing multiple scientific breakthroughs.
Steven brings great research ability to the table but tends to arrive at conclusions prematurely because of missing analysis and understanding of biologic processes. For example, I lamented the fact that spacing of Direct injections were separated by too much time. This was explained by NWBO as a safety related concession for Phase 1. FDA also slowed the trial down to assess safety related issues as first in man. This did not appear necessary based on historical evidence but probably acted as an insurance policy for FDA and is part of a fairly consistent pattern they have used in the past.
Spacing of injections and number of injections is critical to the immune response build up and immunosuppressive response to the treatment. I explained this to Steven before on a Seeking Alpha article. He conceded this point reluctantly by saying that this might offer a little more hope to eventually seeing clinical responses based at least to some degree on recist crteria. My main point was that dendritic cells on average only live a few weeks and educated Direct DCs will not last even that long in the tumor microenvironment as hypoxia causes lingering DCs to become circulatory DCs which leave the site. Some D Cs will pick up antigens and move to the lymph to educate T-cells while those that don't are still needed to regulate the tumor environment with proper signaling activity. If disregulation occurs too soon the immune response can not achieve sufficient strength even if immune memory with T and B cells has already begun to have an effect. This is a critical process to understand and why injection spacing, number and number of cells in each injection is so important. They need to get this right before they can reveal Direct's greater potential.
Quote: What's good here?
All patients are living longer and that is a GOD sp.? dilemma.
vator,
I may have misread the protocols when they were posted here but from recall I believe they allowed for great leeway with regard to treatment options. I also recall that all benefit received would count towards OS which is what this trial appears to be waiting on. An early regulatory decision based on data, if already received, is also possible right?
By the way, I am not a doctor nor do I pretend to be. It's a handle that I chose to use out of respect for those who are. I have a degree in a science based field and have been licensed in the past to use toxic to very toxic materials. I am familiar with scientific language though sometimes find that I must cram it in with multiple readings and learned familiarity with terminology. I am a big picture focused investor that is willing to burn my brain in the worm holes of the technical to gain better understanding when and where needed most. I also buy, hold and buy more if the opportunity presents itself with stocks that have passed a confidence threshold I assign myself.
On an unrelated topic and with regard to Mr. Woodford's involvement with NWBO, I accept that he is a respected investor but I believe his interest with regard to NWBO does not represent Linda's or mine well at all times. I would like NWBO to succeed on their own as much as possible and I believe this is possible. I would also like to see a movie or more likely a TV series made about this company someday and cancer survivors and their families causing theater box offices or TV ratings agencies reporting records for a documentary.
Evaluate,
I believe your conclusions are correct but I do not wish to hazard a guess as to how many might not take DCVax at crossover since Dr. Linda Liau did not. She only hinted that there might be some. This suggests a group of late progressers in the SOC and, to a lesser extent, earlier progressors in the treatment group that might think that they had already received the vaccine and would not have any more benefit from taking the option for whatever reason. This might include cost of checkpoint inhibitors or other treatments or desire to try another trial if permitted to do so.
edwick709,
I definately like "MECHANISM" and "ALL" in your post. I believe that Direct has the potential to reach that or almost reach that mark. Good catch.
I hear you flipper and some of all the ruckus with regard to big pharma seems to have occurred when Linda mentioned the "gentleman from Roche". Evidently Mr. Woodford thought NWBO was engaged to be married with him and his plans with British pharma. Whoops! Not all those who make plans are on the same page as the hedge funds found out last April with options. Lots of drama but don't count out PEI leverage over German insurance carrier resistance at this point. FDA is not the only one with a voice here.
Rkmatters,
Quote: I want press releases of information but in a fair and balanced format.
Here, here! You and Austin get my votes on this matter. Let others be the ones accused of bias and misinformation. The science can stand on its own 2 feet quite well if presented properly. Dr. Bosch is more than capable in this regard.
Dr. Linda Liau said "all patients are living longer". She then went on to say "hopefully" with regard to crossover option patients who didn't get anything, ie. DCVax, and may have gone on to other treatments without it. In my opinion, it is these patients who, as a group, are receiving some benefit from treatments like checkpoint inhibitors and are part of the "all", that she hopes will show that DCVax treated patients will benefit more than.
flipper44,
This KLH/placebo observation in the CLDX Rindopepimut trial you allude to might be the critical difference to trial success that has Adam on edge. His support of CLDX, and most of his recommendations for that matter, has much to do with the business end and not necessarily a good understanding of all the key components of the science utilized in each trial. That constant level of detail would keep him from being able publish with a wide net about so many biotechs. I believe one of the reasons he is here, though not the main one, is for the discussion of the science which is fascinating.
Dr. Linda Liau, in a round about way, really seems to be focused in her video presentation on the OS endpoints and how FDA will react to obvious synergistic effect seen between chemo, radiation, DCVax and perhaps TLR agonists with the parallel trial. There may even be crossover cures being seen with use of checkpoint inhibitors. Adam wants to paint all of this as a negative by assuming that FDA will be dogmatically rigid if the trial does not actually exceed primary endpoints and or provide a clear secondary endpoint separation of at least 2 months benefit in OS. This is fine to suggest as a possibility but FDA guidelines indicate to me that the 2 month OS benefit alone would be sufficient in GBM since there is a great deal of supporting evidence from multiple sources that DC treatments create synergistic effect.
edwick709,
I believe you are closer to understanding how DCVax-Direct works than you realize.
Evaluate,
I am not fully convinced that February or September are the only months that PEI would or could announce news but that seems to be when they do publish many of their decisions. They do an annual published update of aproved medicines, if memory serves, and I believe it is published in February. They also tend to make decisions over 1 to 1.5 years and more than 2 years would be exceptionally long. I also believe that the last German site added in the clinicaltrials.gov listing indicates that the last patients for the trial portion in Germany are now enrolled but at least 4 months beyond the enrollment point are needed to assure that data from these patients will be used for the trial as 5 treatments must be received for that to happen.
Ready,
A quick look at the long term charts tells you that Adam published his piece on the day that the long term bottom and short term double bottom would hit. This was, in my opinion, an obvious attempt to push the price through this point. The attack did not achieve its objective and now we have the rebound that is typical of a normal cycle headed towards good news and funds rebuilding their positions. I expect this may be a sign that many small cap bios have hit bottom and more specifically to NWBO, that the PEI may have something to announce soon as February is a big month for them as is September. If not now then September when the primary completion occurs. FDA may or may not be ready yet so that may cause some delay but perhaps not if they have made their review of data a priority with regard to cooperation with the other regulatory agencies.
I again bought near the low at $1.86 and have had the order in for about 1 month. I wasn't sure that a walk down to $1.85 would leave me enough shares to buy. MMs are pretty predictable. I have another order in at a lower price which was there in case market conditions and the expected hit jobs before options expiration created an even better opportunity. I told Steven I had a plan and now I'm telling you. If you want to see my cards you will have to wait for results just like everyone else. Best wishes.