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Rkmatters,
Amen! Preach it with me sister 'cause we're gonna have a revival. The dying will be given life, pagans will become believers and ravenous wolves will be caged and tamed.. by Linda, the shepherdess of NWBO. LOL!
autologousvax95,
Thank you for sharing and hope you are making good progress getting back on your feet. Best wishes.
austinmediainc,
Do you remember when I suggested that one of the strategies that I thought NWBO would play is to get the trial ethicist to become proactively involved for positive reasons to put the onus of ending the trial on regulators? I said this because Linda stated that she would not end the trial early and would only apply for AA when the trial was completed. This suggested to me that a regular approval path was still being contemplated but would change to AA if everything lined up with all the necessary approvals for manufacturing and commercial ramp plan.
OS eventing has been delayed according to Dr. Linda Liau and as Rkmatters has pointed out this would mean that OS eventing for the entire group is taking longer than 28.33 months according to the original protocol that Rkmatters shared. Remember Pyrrhonian said one trial, the best he could find, showed 30 months median OS for control (treatment arm did worse), well Dr. Liau's comments were from back in October of 2015 and we still do not have 248 progressions reported, which most agree would be a material event, so rest assured that the 9 months that have passed since Dr. Liau's comments is very significant. The OS for the entire group Pyrrhonian mentioned was less than 30 months. If the entire group is living longer than 28.33 months on average then the comments Dr. Liau made were pointing to patients living longer than the best trial results ever recorded and that was 9 months ago which was about 2 months after the discovery of the screening halt. Now couple this with the fact that the parallel pseudoprogessor trial, with more mature data, also did not fully enroll and the chances that an ethicist intervention and regulator actions occurred rise dramatically. If this did occur, then pseudos went to the EAMs program which several posters indicated did happen and Phase 3 treatment arm may have continued enrolling after the screening hold but not the SOC arm if a large enough trending gap in OS had been observed by regulators if they peeked. With this action in place the company would need to wait for events to continue to accrue and report these events on a regular basis to regulators. If SOC was no longer being given then the possibility that a few spaces were left for SOC plus crossover option, to be filled if needed for powering, still exists. The final decision then would be a stop for efficacy (without resumption), "continue" for powering or neutral determination (resumption) or "futility" (no resumption). Futility seems to be a very remote possibility with the evidence from above so that leaves 2 options which are either a positive stop or a neutral to slightly negative continue. The possibility exists, therefore, that an ethicist working on the trial for NWBO may have approached the company to suggest a halt but Linda refused.
Linda has stated that she wants to finish the trial and there are good reasons to do this as recent comments from FDA about regular approval applications suggest. Linda would want FDA to make a determination if she thought the time spent reviewing data might help improve final determined PFS and or OS benefit and chances at approval. Under this sceario Linda would have some idea that positive findings might be expected but would not know when the exact time for median(s) or other statistically significant trends would be found as this would be partially determined by when regulators decide a peek is necessary and what they find. The final decision, and the screening hold of course, would be in the hands of regulators whether or not NWBO remains blinded through this process. Would the company even hint at this if this was the case? Of course not because trial integrity is at stake and powering of the trial may be as well to a small but potentially significant amount so crickets. In the mean time the hunters and trappers quietly follow the tracks and listen for the howls. Best wishes.
chinatown1980,
So what you are saying is that: 1) There really is no need for blinded trials because the market always figures everything out from leaks before the trials are over anyway.
2) FDA is just a puppet and the market is never surprised and always right because the truth doesn't matter and the market can create it's own reality with its supreme knowledge.
"Deep Capture" kind of stuff right? Best wishes.
Jack2479,
They use this treatment first to clear the leukemia then offer patients the option to receive a bone marrow transplant to achieve immune memory. This transplant is dangerous and can kill some patients but immune memory does seem to be achieved with those who have successful transplants which to date has been around 70% I think. U PENN has connections to NWBO technology which moved towards solid tumor research while U PENN went more towards blood cancers. Best wishes.
Rkmatters,
I definately see where you are coming from with regard to AA but Linda said they would ask for AA at the end of the trial and my assumption about that is that ascribed benefit is based on proven PFS and proven OS at the time of approval and not the additional PFS and OS that might be derived after an early stop. Temodar seemed to be willing to leave benefit on the table for the chance at earlier approval but I don't think Linda would do that as long as all patients in the trial are receiving the best care possible. They have gone through too much to leave it hanging out there for a protagonist to take advantage of with a lesser treatment.
The major limiting factors for benefit in this trial appear to be spacing and the very thing that your nephew experienced which is the 3 year cutoff for receiving treatment so the trial can have a chance to end. I thank the Lord that you are giving the energy derived from your love for your nephew as legacy gift to current and future cancer patients as is Dr. Linda Liau for her mother and Linda Powers for her dad. Blessings to you.
sentiment stocks,
Great find and I would add that there was an announcement or something I read that NWBO had spent more on statisticians so that led me to believe they were working on an ongoing event related analysis. Keep in mind too that Temodar appeared to have more benefit than what has been ascribed to it but because the trial ended as it did no pursuit was made to do another trial to determine what that might be. Linda would not want to leave anything on the table at this point. She would also want all patients to have the best possible outcomes. Could it be that after the screening hold was put in place that there might have been a completion of the treatment arm with room left for SOC at the very end if needed to strengthen the confidence level? As long as the company remains blinded I would think that this would be possible. If a BLA was applied for then this becomes mute point. Best wishes.
foxhound02,
If you meant NWBO won't be the ones with next Gen immunotherapy you might want to do some DD on the implications of their patent portfolio again. Rkmatters is very good at that so you might start by reviewing some of her previous posts. Best wishes.
sentiment stocks,
FDA is definately changing and catching up to the need for personalized medicine.
jondoeuk,
The Dr. Prins video made this clear as one of the next steps for future research as DCVax causes renewed or de novo T-cell infiltration. From these T-cells Dr. Prins said they plan to identify and harvest the more potent cancer killers for cloning and reintroduction as supplemental activated T-cell therapy. The combination of DCVax and select T-cell therapy, especially those selected from neo antigen derived activation, is expected to be very potent and well controlled by immunoregulatory responses and help to establish memory T-cell lines. Best wishes.
Turtle65,
Actually, Rkmatters is taking her cues from Dr. Prins and others. DCVax-L is expected to help mobilize key T-cells which will be harvested and cloned and can then be reintroduced at a rate controlled pace. This is possible with the potential use of various tools. These include the timing of checkpoint inhibitor use when tumor burden is reduced and specific types of immune suppressors if the immune response becomes too agressive which should not happen if treatment is tailored specifically enough for given patient situations. Best wishes.
foxhound02,
The early vs late portion of the comment is regarding PFS as a "What if". The bigger picture is the ethics with regard to survival. If a difference in survival is being noted between early and late treated patients then if that difference is big enough the suggestion is that an ethicist intervention would occur and those who are in the screening process would be allowed to enroll but only in the treatment arm. This would leave the trial with a potential need to add SOC patients if accruing data does not show continuing trend of improved survival benefit difference to the point of independently realized statistical significance. The pseudo trial seems to have experienced a similar need to resolve an ethics issue as well as that never fully enrolled either. The pseudo data can be used as supporting evidence in at least that group but if the whole group is eventing later than expected by a wide margin then regulators would have needed to be advised in the Phase 3 as well and they could have been given the UCLA screening tool to use to help verify where patient benefit would have been expected to be seen for all patients in a blinded fashion and then where it actually was seen if they look at unblinded data. This process would then tie into the screening comments made in their press release about the new screening suspension. Best wishes.
iclight,
In other words NWBO's DCVax-L Phase 3 could be way over enrolled with treatment arm patients due to ethicist intervention recommendation but may need more SOC enrolled if necessary. All the negative banter after the screening hold then becomes what? Kind of like trying to turn good news into bad while we wait right? Killer wait no doubt but one I am glad to be part of on the outside chance (based strictly on historical odds) that this treatment will help many cancer patients live better, longer lives.
iclight,
That is one interpretation of final outcome of the Sawston property. There most certainly are others. Best wishes.
austinmediainc,
The one year time frame for regulatory resolution of certain matters is not set in stone but several types of responses from regulators are often answered within this time frame though some can go longer. There are also multiple primary estimated completion dates timed for September from NWBO trials. This is a clue as to what NWBO had in mind for converging various sources of information. Let's not forget that 2 year survival from Phase 1 Direct is coming up soon as well. Regulators get active again after summer breaks and significant news often comes out of meetings in September as well as early in calender years after the fall and winter holidays.
As to your question about ongoing submissions, that was confirmed in the 5-2-2016 operations updates press release. "The company is in ongoing dialog with regulators, and providing further information." I worded this as "ongoing submissions" which may have tripped a key word trigger that you responded to since the word submission is so often used with a BLA or other type of formal petition to regulators.
As far as the news release about their internal and external investigations maybe, just maybe there is something much bigger going on behind the scenes and so they wait out both investigations perhaps at the behest of investigators. Could it be possible that the recent changes in law towards states rights might be the impetus for bringing a case against protagonists of small biotechs? Could NWBO be a prime candidate as a lead plaintiff in a federal fraud case? We can question Linda's motives all we want just like we can wonder who has a vested interest in NWBO and who does not on this board. The bottom line is that motives are best determined by final outcome so we theorize now and wait for results. Some will be proven more right than others with what eventually happens so we wait. Best wishes.
Turtle65,
Whether or not the trial is completed by September or not, the month itself is a very active one for both US and European regulators. The screening hold will also have been ongoing for more than 1 year so some type of news should be expected around that time especially since ongoing submissions have been taking place on multiple occasions since the start of that screening hold about a year ago now. By the way, a lobbyist connection might mean the internal investigation is wrapped up. I don't think any high level government official would want to have questions asked about their lobbyist connections to a sullied company run by an ex Enron VP now would they? Best wishes.
Rkmatters,
Spot on. Questions for you, TC Trader and others. Now that we are below $1 and the ask price is severely restricted, how can the price jump dramatically unless the stock stops trading and the price is reset before the next trading day? Is the preopening price the next trading day then allowed to be set initially by a market maker? How are the restrictions on the ask price and potential price action different for stocks under $1 and those over $1? DNDN was well over $1 both times it shot up. By appearances, those who anticipate good news are hurt by not having the ability to have high ask prices on the books. This also seems to me like those who have standing sell orders in and don't remove them before the opening bell would get hurt and shorts trying to cover at lower prices would have a chance for a while to take advantage of regulated sell prices. Hope you or others are willing to help clarify and present likely price action scenarios with potential types of good news/bad news events. Thanks and best wishes.
afford567,
I whole heartedly agree. Just trying to point out to iclight that he is incorrect about the threat of bankruptcy because of a late mortgage payment. Lots of "woe is me" hand wringing over things that are not front and center issues. I mentioned the possibility of reworking the mortgage as one of the reasons why bankruptcy is not yet in the cards. Best wishes.
vator,
Thanks for this post. This is one of the posibilities in the "about 7 arrows aimed at one target released to hit at about the same time" comment I have made several times now. The business model seemed to me to be designed to protect shareholder interests (survival and Linda's ownership above all else included) until all major threats have passed. Then, at the right time, a merger could be announced that would rock the house if and when the technologies are validated. The MFN clause is only needed up to the point of validation. After that, competing interests would create fair value and make an outright buyout of a merged NWBO/Cognate company almost impossible without Linda's consent. First things first though, so let's see what happens between now and the end of the year with a nice little nod towards September along the way. Best wishes.
iclight,
Cognate is in on the Sawston property as well so the mortgage will be paid or possibly reworked. If there was no way to remedy the mortgage situation by raising new capital again or some other means the share price would be under $.25 already in anticipation of default. Best wishes.
john1045,
Good catch. I have plenty to say about CXCR4 but at the right time the company might too so I wait for their timing. What they have said already was enough for me to put 2 and 2 together. Best wishes.
sentiment stocks,
I guess Pyrrhonian missed the early vs late comparison mentioned by Dr. Linda Liau. I guess it's all about how you interpret language. LOL. Best wishes.
Pyrrhonian,
Have you ever stopped to consider that phagocytosis happens to help prevent overcrowding at the lymph zone with improperly activated DCs? Remember your argument about the low number of actual tumor associated antigens? Now couple that with NWBO's observation that certain DCs produce greater amounts if cytokines and what can you conclude? Well the studies that have been looked at on this board indicate that low numbers of TAA activated DCs still can produce a robust immune response. The numbers may be quite small but the response is what matters and smaller numbers do not always hurt the T-cell response. This is a critical flaw in your analysis and one the Dr. Prins and Dr. Liau have already indicated is pretty much a mute point. They know how to get a T-cell response, which they believe they can improve upon yet, and even big pharma acknowledges this indirectly with their own research.
doingmybest,
Using 2 approved drugs in a trial certainly would speed up time to commercial use after approval since manufacturing would probably already be in place. This would be especially helpful if the effect is expected to be fairly quick and or dramatic based upon proper choice of endpoints and or subgroups. Best wishes.
sentiment stocks,
ONTY was working along a pathway that looked interesting enough to get big pharma to get involved. The lipid pathways are important because research has proven that cancer can not survive certain types of lipid imbalances because this will cause appoptosis resulting in tumor destruction. This particular ONTY lipid based treatment itself was insufficient to cause this nor was there any indication that they were trying to achieve this from what I researched about it. Rather, they believed that critical antigen presentation could be achieved and this proved not to be the case. This was part of the single pathway target approach that has so often failed. I was looking for a treatment that had a multi target approach which is why I originally had IMUC, Agen and others in my portfolio. As I continued on with my due diligence into each I came to the conclusion that NWBO had the best long term approach with their science. Having both intradermal and intratumoral treatments in their DC arsenal was important based on the findings of Triozi et al which suggested that their use in combination could be synergistic and change the tumor microenvironment. EGFR targeting had been gaining some success and circulating DCs could get to where they were active so if someone could figure out some critical activation or genetic modification routes to help DCs do their job then there could be some really good outcomes. Epithelial and endothelial targets combined are even better. This is like attacking undesired plants from the inside and outside at the same time and at the same time stopping seeds from spreading out and taking root.
sentiment stocks,
Well said.
Sorry for the missed autocorrect spelling error in my last post. I sent the post with the intention to proof read it before getting timed out. It should have read "breast cancer". The autocorrect did the same thing with this post before I corrected it. Best wishes.
Rkmatters and AVII77,
The bottom line is that breastfeeding cancer treatment has seen improvement in treatment outcomes over the last 40 years or so. Improvement in outcomes for GBM have been next to nothing except for improved resection techniques and Temodar. FDA will add to the GBM arsenal anything they can find that is statistically proven. There is no way these treatments are either or unless one is a proven cure for some specific patient population on its own or in combination with another treatment. Ethics trump all other arguments which is why the pseudo trial is so important and crossover OS benefit must be carefully considered. I understand AVII's concern well because there must be absolute proof of efficacy.
PoorMan,
"These findings emphasize the need to more clearly understand the cellular mechanisms by which DC vaccination induces effective tumor-specific immune responses."
You mean like have a scientific advisory board look into optimum spacing of treatments for maximum benefit and minimum cost? Sounds good to me. Best wishes.
exwannabe,
There was probably only a very narrow window of time when DCVax-Prostrate would have had some serious attention from anyone. Big pharma didn't like the business model chances for success let alone limited benefit seen to begin with. Then when Provenge was approved up until DNDN bankruptcy the challenges became obvious even if better management could have made it profitable to a limited extent. During this time frame DCVax-L might have had some interest shown simply because they had a better process in place to control cost of goods sold. The main problem for NWBO would have been they never had enough money in the coffers to partner with good terms so the study would have been nearly completely in the hands of a partner if there was an offer of some sort actually made. That offer, if ever made, may have included rights to additional indications for the base DCVax technology as well. Too much guessing here, I know, but that is generally how it works with a cash strapped company.
Pyrrhonian,
Cellular therapy became a national priority in Great Britain when the DCVax-L trial became designated as such. Since that time, government funding there has begun to be used to increase cellular therapy production capacity with the building of new facilities. Granted the multipurpose nature does not directly tie in to NWBO but the fact that their readiness seems to be coinciding with Phase 3 completion should not be overlooked. Most other cellular therapies are many years away from commercial production launch let alone capacity and would need others to fill the gaps for them in a fairly big way if and when they do come online. Even those who do have nearer term anticipated production runs are expecting very low quantities compared to what most investor expectations have been. Why? NWBO, through Cognate, does not have the same expected wait time for ramp up so with Great Britain bringing capacity on line fairly quickly we need to be thinking about why there is an obvious priority based need for this right now especially when others seem to have their low expectation runs already covered.
flipper44,
There is that September thing again and wasn't the EAP where those missing pseudo progressors that sentiment stocks was talking about ended up? Crazy huh? Kind of seems like investigations, trial readouts and manufacturing news could be like about 7 arrows all pointed at the same target and being released so they hit at about the same time. Let's see what they come up with to deal the August payment needs. Best wishes.
AVII77,
Thank you for the time you took to respond. Much appreciated. Best wishes.
doingmybest,
Thanks for the input. Your shared experience is a valuable source of information with regard to the potential reasons for delayed announcements. Best wishes.
Pyrrhonian,
Your numbers need to start with your base average cost between various DC manufacturers and then add in the cost of developing, implementing and validating, through regulatory approvals, the cost of automation for 2 different cellular products on multiple continents and at least 4 separate sites. That might run the cost up a bit right? Then add in the cost of proof of ability to ramp up to expected commercial production levels to meet anticipated demand estimated not only by the company but also by regulators that is necessary for receiving BLA approval. Mo money right? Keeping it all confidential.. priceless. Both the pre-revelation stock price and the potential the revelation holds. One looks like a zero the other like a 1 with multiple zeros behind it. Conviction is a funny atribute because it is often confused with stubbornness. What you are convinced of I am not. If I was convinced as you are about your concerns then my actions would be stubbornly foolish and stubborn would be a justifiable tag line for me. For the time being I stand on my convoctions. Best wishes.
Pyrrhonian,
First of all I agree that FDA would not cause a temporary halt of a trial just because commercial scale manufacturing was not in place. That would be an issue only if a BLA was in place and the company was waiting on a response which would include a review of manufacturing preparedness. The question about the temporary screening suspension had to do with another issue then unless we know for a fact that a BLA is in place. The problem is we don't know for a fact that a rolling BLA is not in place since FDA keeps requesting additional information.
The real wild card here is how the pseudo progressor trial might fit into everything. Something was changed there very quietly and without any fanfair which is highly uncharacteristic for NWBO according to the bears aND many longs wold also agree. We know that they were going to be added into the Phase 3 results if the Phase 3 could pass muster on its own. Are we waiting on trending results from the Phase 3 to do this and response from a petition to use these combined results without finishing the planned enrollment? This may not involve a BLA if the pseudo trial was halted for positive ethical reasons but then again it might right?
Another point about early vs late tratment data being uniterpretable is pure speculation on your part. If later patients are doing better than earlier ones they would dig to find out why not condemn the trial. Best wishes.
Pyrrhonian,
Are you saying that a BLA won't receive a CRL if an approved, scalable model for commercialization is not in place on time? That is not how I understand their final approval proess.
flipper44,
That theory is a good theory for the positive outcome that aligns with the pseudo trial activity, the comments by Dr. Prins and Dr. Liau and the obvious build out of manufacturing. This is more than balanced out right now because of the current NWBO financial condition irregardless of cause, the silence irregardless of cause and past history of missed deadlines. For many this represents more than sufficient evidence that a positive near term outcome can not be achieved. Those who have been warning of this danger, whether eventually proven right or wrong about specifics, have been right to warn about the price direction. Buyer beware is a very necessary message no matter the source especially in this sector. With this said, I still believe the positives mentioned at the top of this post will have enough time to play out and I still plan to add to my position between now and the end of this year as timing and circumstances dictate and or allow. Best wishes.
I meant minority partner with Cognate or Toucan for a large equity stake. I'm not saying they would need to do this but the option is always there which helped me see a way that the investment could be derisked to some degree and NWBO stock value could be at least temporarily manipulated by the company with financing news generated on favorable terms for all investors. Without commercial manufacturing build out this would have been a longer term loosing proposition. At this point it makes much more sense.
maverick 1,
Happy 4th to you as well and thanks for posting. There is something Linda and Toucan can do to raise equity which they don't want to do but could and that is to take on a minority partner for a large equity stake. This is another leverage point they can use to avoid drastic measures and improve the value of their stock in NWBO,