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Rkmatters,
That is what happens when someone compares a year and a half or less of analysis and insistence on absolutes with 20 years of research that has led to proprietary patented technology. I enjoyed seeing flipper44's freight train like picture of DC migration associated with lower dose vaccines. Best wishes.
flipper44,
I didn't go through very much yet but immediately noticed their validated cutting edge ability to improve the cell selection process. That says it all right there. NWBO has the sauce and Frauhofer selects for maximum potency. Massive step forward. UCLA dream has just been bumped forward to present tense. Best wishes.
antihama,
There are enough hints from the company and from German claims that a closed system is the most desirable form of manufacturing for both safety and reduced cost of goods longer term. The delays leading up to German enrollment point to this as well as the potential need to restart enrollment as a backup plan for equivalency failure. I am pretty sure the Germans might have been interested in helping develop an improved closed system for Direct as well. Those systems may have already been installed at Sawston back in May. My guess is that Sawston equipment may be undergoing some fine tuning before the first approved run is performed for the upcoming trial. Best wishes.
flipper44,
So do you think TFF or possibly improved TFF is the reason for optimization and or that Fraunhoffer helped them finish and implement the use of a fully closed system for their part of the trial?
Rkmatters,
DC modifying terms like subsets, phenotypes, activation type, maturation stage and "in certain conditions" go to the heart of what DC specificity for safe immunomodulatory regulation is all about. Anyone who lumps together, generalizes with or discounts the importance of how these terms are used to describe specificity is not acknowledging the very nature of DC characterization. Researchers have known that specificity is intrinsically related to immune response for a very long time. Overlooking this in relationship to research with DCs would be counterintuitive and yet this is exactly what some have suggested has been happening because NWBO and UCLA didn't and still doen't know better. Even AVII concedes you can't cover up the fact that OS eventing has been slowed down in the earlier trials and seems to be hinted at in this trial as well. Best wishes.
john1045,
Thanks brother. I appreciate all you have done over the years to contribute here on ihub and elsewhere too. Death and Hades may be the last enemies to be brought to justice but when cancer is defeated it will serve as a good kick in their teeth before that day comes. Best wishes.
Pyrrhonian,
You are fishing if you think I say what I do for making money. I plan to make money when the science is validated not before. You are also fishing when you focus only on the T-cell response. There is much more to this than just T-cell response which is why I told you about the importance of spacing before and that is not even all of the story. Systemic response must be achieved and this requires a sufficient cytokine response locally and systemically and this must be controlled. There are indications that NWBO is very close to finding the proper balance. Best wishes.
reg2015,
Hang in there brother. We fight the good fight for those who have gone before, those who are currently in and those who will yet be called into this battle on the front lines down in the trenches as you have been.
I will not soon forget Ben Hodges who shared his wife's ongoing battles with us. I had hoped she would be one of the long term survivors but now he and his kids are without his wife and their mom. I believe her part in the Direct trial was inspired by hope but also in the willingness to try and help others from what would be learned from her experience. In a very real sense she shared her experiences and gave her life for all of us. For that I am grateful though saddened because of the price she and her family have paid. Her children may not understand now but someday they will know that she wanted the best for them and was willing to be a part of helping to change their future and that of others for the better by taking part in this study.
I pray that you and all cancer patients will one day very soon be able to say goodbye and good riddence to this hideous disease and the failed treatments of the past. Best wishes.
Pyrrhonian,
I do like the results from the Phase 1 Direct trial and it has to do with correlations mentioned and the distribution of longer survivors as related to likely trial design. It also has to do with correlations that I believe are purposely not mentioned but which appear to be very much related and biologically in line with the named correlations that have been observed. These undeclared correlations have to do with something more specific than just method type but are also related to some degree with method type. There is too much at stake to say more which is why I have not sent my notes to Larry Smith though I was about to send them to both of you over one year ago. When you took the bear case on I decided to wait and watch. When things started going South I realized there were things happening that began to call Mr. Woodford's plans and contribution into question. I have been around long enough to know what the play book looks like when it comes to targeted manipulation and to what degree some are willing to go to achieve their plans. If you have never seen the movie "The Constant Gardener" you should because it is based on real events that involved big Pharma executives from Great Britain. I am sure Mr. Woodford knows this history well. Best wishes.
Pyrrhonian,
Sorry about my last question about your investmemt strategy coming late. You explained yourself well in this post and I am just catching up but in additoon to that and after all I told you about spacing and expected MO I can't believe you are still doubting the direction these results are pointing towards. I am not saying this direction is a validated conclusion but it is following a predictable pattern right now based on correlated biological activity. I warned Adam a long, long time ago that he would end up wrong about this one. They have had plenty of time to find a way on to the life boats. Best wishes.
Pyrrhonian,
Have you moved back in yet on a straddle? Best wishes.
marzan,
There is quite a bit of emphasis on debt type structure and limitations. Maximum of all security plus debt is $200,000,000. Also multiple points of emphasis on needing 66 2/3 % of voting stock to overcome previously implemented barriers to unwanted takeover or other actions. I may have not recalled correctly how many times mentioned in prior announcements but this time there seemed to be more repetitions of same. Best wishes.
hankmanhub,
If an equivalency comparison was being done, they needed the option to continue enrollment if passing equivalency was going to be a problem. Silence would normally be maintained if ongoing communication between the regulators and the company was ongoing especially if more than just equivalency was involved. Best wishes.
hankmanhub,
Statistics help draw a reasonable conclusion about cause and effect. What you speak of is validation not predictive value. When validation arrives a stock price can change while the markets are closed and the unrealized intrinsic value becomes realized value. Observations, on the other hand, can be used predictively. The more accurate observations that exist and can be studied, the more precise a prediction using those observations has a chance to be. NWBO management has been investigating and observing DCs for over 20 years and much of the latest research with regard to DCs is demonstrating that DCs can indeed be trained or activated to respond in a very precise manner to given situations. They also have one of the primary costimulatory effects on the immune system. DCs have different roles depending on their activation and source type. Those who understand this best are those who have been studying them enthusiastically the longest and NWBO is one of the leaders in this regard. Recipes get refined over time and NWBO has the secret sauce. Best wishes.
hankmanhub,
flipper44, myself and others are looking at all of this as outsiders. What flipper44 is suggesting is what I agree with as well. We can not know what each step he speaks of entails specifically but if what we see along the way matches or comes close to our expectations then we have greater confidence of being on the right path. I expected spacing of treatments to be a problem. It was. I expected to see necrosis in responders. They saw that. I will not get into more specifics about why I expected these things to occur but it has to do with the observations NWBO has stated.
Let me share one other variable that flipper44 did not discuss. Besides there being 2 activation methods there were also 3 cell counts in each method utilized. That leaves 6 distinct combinations amongst 40 patients. Not all dose levels were administered equally to patients. The lowest and middle cell counts per vaccine had the most doses administered. Besides this, some patients were being treated too late because of first in man designation and some patients early on were allowed into the trial when they were too sick to wait through screening before treatment and they did not do well. Those would be patients found in the lower part of the results nto listed. The screening requirements were changed to treat slightly better prognosis patients to overcome this obstacle which the patient by patient rating for expected survival took into account. To answer your question in a few words.. too many variables to produce good efficacy results for MOST patients. That will change in Phase 2 big time. Best wishes.
Turtle65,
Mr. Woodford is not easily moved to invest. He is experiencing a temporary setback which was in no small part created by his actions. He did not invest based on misinformation about the science and I guarantee you he is excited about Direct no matter what delays this company experiences in the interim with L or Direct. He typically holds for 5 years. His fund is called Patient Capital for a reason. Hang in there buddy. The movie rights alone have to be worth about 5 million dollars and you might get a well paid minor role. Best wishes.
Rkmatters,
I agree with your rational and that of flipper44 and others who realize that by trial design the end of the trial was to fall within tighter parameters. I still believe that we will hear something soon but if something really strange with manufacturing happened, they would want the trial to continue while they got that worked out. AVII theorized that the PFS 248 event mark could be kept hidden by asking for a coprimary endpoint. Perhaps this could be incorporated into a confirmatory trial based on OS which, if granted, would allow them to chose to announce the PFS results at an appropriate time after the manufacturing issue was resolved. This is rather far fetched but seems to be possible and with this company and this trial quirky happens. Best wishes.
HappyLibrarian,
Linda said they would seek AA at the end of the trial. They said they did not plan to end the trial early even with DMC recommendation. The considerations for this have been discussed at length and focus on the long tail of survivors and delayed benefit. We are either very near to some type of news about the L trial with regard to primary endpoint as primary endpoint plus analysis would typically take at least one month past a scheduled primary completion date (ie October/November) or we are up to possibly another year away if we move into 2017 with no news as this would fit more into AVII's observations and assertions about a possible coprimary endpoint. Rkmatters filled us in more on this in her discussions with AVII.
One thing that investors need to understand is that the projections of demand will need to be matched to a realistic time frame to meet it. Specialized equipment, the right kind of space and certifications for use are needed. The need for clean room space must be replaced with automated processes if demand will ever have a chance to be met with a potential breakthrough therapy. Germany is notoriously diligent (slow) with this certification process but they do have an incentive to prioritize (move faster than normal) this time. Slow eventing mentioned may have given NWBO a cushion to get manufacturing processes lined up better while they wait. One of Germany's scientists was a co-recipient with Dr. Ralph Steinman of the Nobel Prize for his work with dendritic cells. National pride is at stake and that is a big incentive. Best wishes.
flipper44,
I am now starting to lean toward the screening halt having to do with rapid enrollment and needing to wait for a determination on manufacturing equivalency issues if both batch and TFF were being tested in the trial in Germany. In this scenario if they needed to continue enrolling due to potential non acceptance of TFF, they probably needed to petition to do so as including TFF would probably be considered their risk. Any problems related to either group would then mean screening probably would have restarted as early as last October if needed and allowed based on type of problem if there was one. Also in this scenario, the ongoing regular submissions being given to regulators may have included required data from both batch and TFF treatments. Delays in granting equivalency would obviously have caused strategical manufacturing problems if demand was increasing for HE patients. Best wishes.
flipper44,
How do you see your options for TFF encorporation into the trial fitting into the discussion about Germany wanting a closed system? There seemed to be enough of a delay before any German patients joined the trial for this to be put into place before they started. Could they have been doing side by side with batch testing and TFF based on prior safe use in Direct and are now waiting for results with additional patients to be enrolled if needed? Do you recall the timeline with regard to the German approval for their treatments being processed outside of Germany? I ask because that may possibly have had something to do with TFF though that idea seems strange to me. Best wishes.
Rkmatters,
And what they saw with all of the interactions between DCs and PD-1, possibly PD-L1 type, combos they also saw with just Direct in their mouse studies without giving us all of these specifics. Kind of makes my heart want to skip a beat or two and join Dr. Stupp and about a few hundred thousand patients to pound on the doors of Congress and FDA. Best wishes.
Rkmatters,
Thanks for clearing this up better for everyone. I just basically went with Dr.s comments suggesting pseudoprogression would not be a problem in this trial after perfusion analysis was done and because early pseudos were being removed. Best wishes.
momentum2play,
This may be true and the list of participants in the program might tell a story all by itself. If this ends up serving the purpose of monitoring naked shorts and their covering, there won't need to be a short squeeze to squeeze the naked shorts. Best wishes.
iclight,
Funny that you say they are waiting on documents when what you quoted said they were receiving "regular updates". Sounds more like everyone is waiting on a "all patients are living longer" kind of problem. Maybe you should just stick to reading what is written instead of trying to read between the lines. Best wishes.
maverick_1 and Stillwell,
Very interesting discussion the two of you have brought up. Perhaps something was brought to BNY's attention. Best wishes.
TC_Trader,
I am curious as to your take on today's action. To me it seems like some more short covering as Maverick_1 sees happening but the early big action seemed different than that. Thanks and best wishes.
Adam_Feuerstein,
I have seen much worse promotion and much worse short attacks. Chris could have found many better stocks to promote than what has been a falling knife until recently. He is here for the science with the hope of being part of the dawning of the age of an immunotherapy breakthrough. I hope you will take the time to peruse the science for yourself and share what you find about the capacity of dendritic cells to modify the tumor microenvironment. Grapefruit juice indeed. Hopefully your studies will lead you to an improved understanding of polarity. You do know that you can make a battery using grapefruit juice right? There is still time to turn from the dark side. Best wishes.
md1225,
Are the folks at Lahey clinic involved with the Direct trial? As far as I know, no one has specifically mentioned that top tier survivors in the Direct Phase 1 trial have had checkpoint molecules inhibiting their immune response. Please explain in more specific terms if you can because NWBO has only used general terms and numbers without the more detailed analysis of time frame responses. Then again, maybe better that we are all left guessing for now. Thanks.
md1225,
Has it been proven that the checkpoint molecules are having an effect before week 4 in the top tier survivors? Best wishes.
maverick_1,
Yep. They are quietly walking out of the theater right before someone yells "fire". Also, notice how quiet some of the more analytical bears have become lately. November was the outlier month for results to come back negative on L and it will soon be upon us. The mood has obviously shifted.
By the way, with your experience what would you guess are the percentage of shares on a daily basis that are going to be locked up for the longer term and essentially removed from the float for a while. Best wishes.
md1225,
Or that the partners are with L only because sufficient immune response occurs early on without checkpoint blockade in more optimized situations with D. Of course if the optimized conditions were created by patients moving on to checkpoint inhibitors after trying D then that would lead to what you are saying. Best wishes.
Sojourner55,
You are correct. Many on this board are not aware that the grapefruit juice comment by Adam Feuerstein came as a result of his responding to a comment I made on Seeking Alpha about Direct coming from behind to take the lead and focus over L as a possibility. The buoyancy we are seeing in the share price now is probably beginning to reflect on this as well as the probability of success for L improving without news on the 248th PFS event. As I said before, IF method B is the reason for the survival at the top of the chart and NWBO makes that news public then everyone and I do mean everyone needs to be ready for the consequences. Did Mr. Woodford see that correlation last year if it indeed exists? I don't know but that would be a very good reason not to be able to trade. That might also have been a good reason for his October financing no matter what his motives might have been. After that point NWBO appears to have called his motives into question. Now he may be preparing to buy on the open market again from those who want or need to breathe. How NWBO releases news may ultimately decide who owns enough shares to influence the company the most. End game strategy in play here folks. Best wishes.
beachlifeisfun,
Fair enough. I just think the correlations have been renamed and adjusted for an unexpected variance. Best wishes.
Turtle65,
Which is exactly why I am excited and less than specific. Best wishes.
flipper44,
The updates on IP would definately help clue us in. I think NWBO was using a cocktail of immature DCs in their Phase 1 Direct trial. There is a phenotype that appears to respond to activation differently than others. Some phenotypes are better at cross presenting to T-cells than others and some are better at releasing cytokines than others. Activation itself is probably being refined as you noted with time differences. The correlations referred to early on also seem to have been renamed. Best wishes
HappyLibrarian,
I think NWBO is busy working on some intellectual property rights issues and a few other things right now that reflect what they learned from Phase 1 Direct and patent applications that they have been asked to refine. I also think they may be getting close to some other news that may be out of their hands. If Mr. Woodford is working independently of NWBO then he appears to be preparing for some type of news as well. If he is working with NWBO now then some type of coordinated effort may be in the works. That is what I was referring to as a possibility in that post. Best wishes.
Rkmatters,
I don't think they want the shorts to start to cover. I think they want them desperate to cover. The news you speak of could be released with more specific Direct Phase 1 analysis, manufacturing and patent application updates and other news to blow the top off as Mr. Woodford makes his move. The problem for longs is that they have been holding their breath for so long and traders will give up their shares easily that the temptation will be to take quick profits. The market in general will need time to digest the implications of the modeling news and projections of the impact Direct will have on the market. The stir caused by Mr. Woodford making purchases on the other hand will get everyones attention. Best wishes.
flipper44,
Agreed. Too many variables can lead to any conclusion you want. Correlations, on the other hand, help to improve the interpretation of data. Disregarding the correlations NWBO mentioned earlier because they are not mentioned now risks giving randomness too much credit. This was the point I was trying to make to Turtle65. Maybe an arrow in the quiver. Best wishes.
beachlifeisfun,
I am no statistician but I did take one statistics class quite a while ago. In regards to this trial, the data presented and it's stratification, could you illucidate? The company stated that there was a correlation to activation type and cell count. These correlations would tend to show up in a non repeating pattern if cancer types are being compared for these variables. In a completely random outcome I would expect to see a greater chance of random bunching of cancer types at the top and bottom depending on probability of such since no correlations would need to be accounted for. Thanks in advance. Best wishes.
Turtle65,
I agree that a note of caution is always warranted but.. I think you should go back and look at that Direct info that was given to us recently. If you look at all the survivors you will see that they are all in different indications. There is no bunching as lung and lung net and pancreas and pancreas net are different types. Sarcoma had 8 patients so the chances of 2 receiving best options was increased and the last patient to event was a sarcoma patient. Apart from this, you will notice mostly distinct cancer types listed as you continue down through the event chart with few repeating types in the top 30%. If you think about the 2 activation types and 3 cell count variations you can put this information into perspective. There were 40 patients. Cell count determines sufficient activation and whether or not cell crowding prevents efficacy. The company early on said there was a correlation to cell count and activation type. Now, how many patients do you think received best activation and best cell count? Perhaps 8 or 9? Hmmm. Best wishes,