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It's interesting that Dr. Liau is not yet speaking about what happens when DCVax-L is combined with other therapeutics. I believe the reason is based on the formalities applied to clinical trials in which nobody speaks officially about advancements until they've in some way been presented for peer review. Let's hope that happens in the near future.
To my way of thinking the entire process of developing new products takes entirely to long. While a company can release a TLD statement, it's very general, just an overall impression of what they've seen, and as we know the peer review can take a year or more before either Journal, or acceptance at a proper conference occurs. How many lives could be saved if the regulators really got into what was seen in a trial and if justified did an EUA to make the product available while all the formalities of peer review and formal filing for approval, often in excess of a million pages, is done over what's often in excess of a year.
It's not that no data has been revealed from the trials at UCLA, interim results are spectacular, but in a formal presentation by Dr. Liau, she's apparently not discussing them. I feel certain that if she were treating a patient with DCVax-L they would also be receiving Poly-ICLC. I don't know if the company is permitting her to treat such patients if they're not officially in a UCLA trial, though she clearly knows how to make the vaccine herself.
Yesterday I saw a neurologist because of essential tremor, which is hereditary as my father had it. While she doesn't suspect anything, she's having me do a brain scan, which I've never had previously. While I've been very pleased with City of Hope, if there we a problem requiring surgery, I'd probably try to go with UCLA and Dr. Liau if possible, only because of the after surgery treatment that may be available there, and nowhere else, at least right now.
If the EUA were used more frequently, I would suspect the regulators would have had sufficient evidence to do so back at the point where the trial was resumed after the halt. I believe the German's insisted that all get the vaccine because they clearly saw the benefits, and the others did come over to their way of thinking. I suppose the other aspect of using an EUA would be having a production facility that wasn't fully approved for commercial production, but was qualified to supply pivotal quality trial material. How many tens or hundreds of thousands of patients might have been benefitted if an EUA had been done back then?
Gary
I don't know if anyone knew the size of the trade, anyone see it?
Gary
I am still curious about the after-hours trade on Thursday. If the trader does have some information, it would have been normal to believe it would be released on Friday. The company, on the other hand, should know that good news is best released early in the business week and does have the flexibility to do so.
If there is anything to this Monday, it should be very interesting.
Gary
We know they have St. Gobain's Glass for production of the disposable cassette, I believe they can produce virtually any quantity that NWBO wants. In terms of the EDEN unit itself, I'm sure that several companies would be capable of either building the entire unit, or building components that the Flaskworks personnel could assemble, test and certify.
I believe the EDEN units will be leased to those authorized to make the vaccine, NWBO will be responsible for all maintenance and upgrades, and I think they'll track each cassette to the machine that makes the vaccine and it's proper disposal. The question is whether Flaskworks will assemble the EDEN's from contracted components, or just certify each unit prior to delivery to the producer, and then maintaining and updating it as applicable. I think that Flaskworks will be a profit center of it's own.
Gary
Thanks, I think I may have after hours authority at Fidelity, but didn't think OTC was covered, clearly it is. Pink's aren't, and that's fine with me.
Let's hope that purchase is based on someone knowing something. The other possibility is someone put in a market order after hours and the MM's took total advantage of them. Market orders have risk anytime, but after hours I believe you're exceptionally vulnerable to MM's playing games as practically no trading is going on, especially in a stock like NWBO.
Gary
I didn't know that you could buy after hours on the OTC, but perhaps on a foreign exchange. If this is real, someone knows something.
Gary
Doc,
To my way of thinking, the real question regarding production of the vaccine is what the capacity is for whatever company, or companies, is for making the EDEN units and disposable cassettes. I don't know if estimates that some made of the EDEN costing tens of thousands each when mass produced, but if true, well over the cost of making it is returned in the first batch of vaccine that's made in it. I believe that if worldwide demand were a million batches a year, we could find, or build cleanrooms capable of supporting 20,000 EDEN units which at 50 batches a year give us 1 million batch capacity. I suspect that CRL could house all, or most of the EDEN's in existing facilities they have worldwide that already have cryogenic, and other support needed.
I would think that if the demand is there to build 10,000 EDEN units a month, at the right price manufacturers will materialize who can do it. I'm not saying that many are necessary if production proceeds approvals, but if substantial numbers don't exist at the time of approvals, rapid production may be needed, especially if off label use in other solid cancers is available.
Gary
In roughly the next week NWBO should issue their quarterly report. Unless we have action from the UK, it's doubtful if they'll say anything beyond the filing there. I believe that if they wished, they could gain an additional week if they thought there would be more to report in the additional week.
As of today, the 150th day is just under 3 weeks away, the company certainly knows if they got an RFI or not, which would give them a clue when they should hear from the UK, but I doubt they'll say anything unless they have something official from the UK. As for anything new on the EDEN, perhaps if something worthy of discussing has occurred, we might hear of it in the quarterly.
To me it would be big news if they broke their tradition of only releasing the formal report, but no webcast, if in advance they PR'd a quarterly release coming on a specific day, and a webcast very shortly thereafter.
Gary
I don't believe that has to be true. Remember, I'm not saying for every trial, but if the DSMB or lead clinician believes such action worthy, it could take far less action at that point to make such a decision than waiting years and reviewing applications that run to over a million pages. I believe a fairly small panel of expert Drs. actually seeing what's happening at key trial sites would take a smaller effort than evaluating a BLA or NDA as applicable.
Gary
You're right Joe, I was suggesting a massive change, I don't know if it will ever be made. I'm sure we've not yet had a filing with other regulators as if we did, it would be announced. They're preparing to do so, but that can take a great deal of time, I have no idea just how close they are.
Gary
I've got to suspect that knowledgeable brain surgeons over the last few years have had their patients tumors properly preserved on surgery. Certainly many of these patients are no longer with us, but some are and may still be in a condition where the vaccine could provide a major benefit. I have no idea of the numbers, or whether the company has in any way established anything with regard to these patients, but I believe for some time the annual demand may exceed the number of new patients expected to be diagnosed in a given year in the geographical location it's been approved in.
As I understand the application, it's for all brain cancers, not just GBM. While that's certainly a bigger number, it's nothing like what would happen if off label use is available for other solid cancers. I cannot say if such off label use can be provided by paying a premium, while the demand for brain cancer demand can't be fully met, or if it only can be added when all label demand is being met. I do believe that new trials will be opened for other solid cancers, but they'll only handle a tiny fraction of those wanting to get the vaccine.
It looks like we were taken down once again at the close, we were down just over a quarter-cent just prior, but brought down by half a cent more at the close. Amazing how the MM's manage to do that day after day.
Gary
Scotty, while I'm inclined to agree with you, it's been a few years since I mentioned it to my back surgeon, who's also a brain surgeon, and I found he knew nothing about it. When I mentioned Dr. Liau's name he not only knew her, but had worked with her and almost immediately he and many working with him became investors. I believe that you're right, brain surgeons throughout the world will get the word on the UK approval and they'll help push for approval elsewhere. I also believe they'll learn of the use of Poly-ICLC and/or Keytruda to enhance the benefits with our vaccine dramatically.
In the beginning, I very much doubt that the supply will be able to keep up with the demand until the EDEN unit becomes available. The biggest sales force in the world is useless if product cannot be delivered. With UK approval sales will be met through Sawston and provide some of the funding needed for the company to pursue the additional approvals which combined with EDEN approval will permit more product to be delivered elsewhere. I'm still of the belief that it will be CRL who'll be doing this production, storage and delivery. As for sales, as the word spreads to the worlds brain surgeons, little selling will be necessary, managing to satisfy the demand may become the tougher task as patients and their Drs. may be unhappy with being told their vaccine is scheduled for manufacture several months from now. A legal question may need to be answered as to whether it's acceptable to accept an additional payment for priority manufacture of the vaccine, if so, I would expect wealthier patients will make such payments.
Gary
Thanks for all the agreement, but sadly we cannot change the FDA or other regulators without immense pressure for change. I believe our FDA has become a little more open to change, but far from actually getting involved in trials and making a judgement for themselves without formal documentation that often goes over a million pages and adds perhaps a year or more to the process. Imagine the difference if the DSMB at 50% or so through a trial told the FDA to come take a look at what's happening here, and if you like it, approve it, or at least permit it's use for sale by granting EUA for now, with further results supporting full approval through a Phase 4 reporting the results of all who received the product.
I suspect that such actions would cut the cost and time required for many approvals dramatically, certainly approval with out a ton of paperwork would save years, and many millions. I also suspect that our regulators would get a far greater sense of accomplishment if they actually got involved in the clinic instead of reviewing a pile of data. JMHO.
Gary
I believe if the regulators would pay attention to the Hippocratic Oath they would approve drugs, like those Anavex has in trial, for broad use, but insist on conformational trials to maintain them on the market. I believe it's clear that patients either see benefit, or are no worse, in essentially all indications the drugs have been tried on. If something better than that were available, it would be approved, but it's not.
To me, a conditional approval is far superior to taking years, perhaps even a decade and hundreds of millions to run further trials while millions go untreated. With the conditional approval, I would have every patient have treatment results reported in a Phase 4 and that too could be the basis for making the conditional approval into a full approval.
I hate to continue saying it, but I believe the regulators should be far more pro-active. They should be looking into trials while they're underway and if they clearly see benefits, do conditional approvals immediately. In most cases this probably would cut off perhaps 5 years and a great deal of the cost of clinical trials and have the potential of saving many lives. I believe that benefits seen in most Phase 2 trials should be sufficient to see such benefits, and a million pages or more to prove it is ridiculous if the regulators could pro-actively speak with clinicians, patients, the DSMB, etc. and make a decision for themselves. If they don't wish to call them Conditional Approvals, call them EUA's. the point is not taking decades to take a product from preclinical development to availability to the patient. They did it for Covid 19, for the person with other deadly diseases, like pancreatic cancer, it's just as important to make miraculous products available in months, not decades.
Gary
The question is well covered by the expression in the TV show, what would you do.
If you're suffering with a cancer and the best thing being offered is CAR-T, but the risk is a future cancer, what would you do.
Sadly we're learning that we really can't know all the long term side effects of all sorts of things we eat, drink, etc. all the time. Some things are rather predictable, like smoking, but others certainly are not. The Covid vaccines no doubt saved millions of lives, but a few may have died from it. Herceptin, and other drugs like Kadcyla developed from it, has been a miracle worker in Her 2 positive breast cancer, but a allergic reaction in a tiny percentage has been deadly.
I believe our vaccine will be found to have virtually no substantial negative side effects, but if applied to millions, if even one passed on shortly after receiving it, it would be suspect unless something else was found that caused the death.
As long as a patient has choices they may not choose CAR-T, but if nothing else offers possibilities, death is the other choice. Some people do choose death over the treatment that sustains their lives, especially when the likelihood of a cure is approaching zero. At this point, no one really knows if in any given patient our vaccine could result in a cure.
In 1994 my wife was being treated for breast cancer with chemo after surgery. She met a gentleman who was given less than 3 months to live with treatment. He and his wife had always wanted to see parts of South America, and his Drs. agreed to a 2 week vacation there provided he take treatment just before leaving, and immediately on return. When he returned, no cancer could be found. I have no idea if his remission was sustained, but believe he lived far longer the 3 months. I don't know if our vaccine could cause such miracles in some patients and we'll really never know until it's tried in millions of patients.
Quality of life often fails to get enough attention, it should be one of the biggest reasons to consider our vaccine. It's rare that a cancer therapeutic not be accompanied with negative quality of life issues, this appears to be the case with our vaccine. Certainly it probably will require others with side effects to achieve big benefits, but the side effects are still far less than SOC treatment, as I understand it.
Gary
Iron Mike,
I'll agree with the fact that the company is aware of what's being said here, but I'll disagree that the company will continue to operate in a secretive style once they really have something to say. LP clearly avoids discussing what the company is doing when she really has nothing new that she can say. I believe this will change dramatically when she does have something to say.
Frankly she went overboard when she announced a date that they'd file in the UK, then had to back of twice as delays that were out of their control occurred. The most I've heard from most other companies was an intention to file in a given quarter, had she simply said fourth quarter she'd have been fine. Likewise, I think time to acceptance of the EDEN is largely in the hands of others, at this point if she said she expects it this year I'd appreciate that.
I don't believe I've ever heard any company say a RFI was received from any regulator, nor do they discuss any meeting they have with regulators, and certainly not any serious discussions with other companies about possibilities, which are always done under confidentiality terms. When something is ready to announce, it's announced.
For years IMGN had been saying they were looking for geographic partners for their drug, Elahere, but at no time said they were actively seeking to be bought out. The announcement of the buyout was the first mention, and it was so far along it was completed in a couple months, whereas the likes of SGEN had taken years. I frankly hated it, though I was certainly better off financially, I believe the company would have been worth far more if they waited for sales revenue to develop.
I'm sorry LP didn't have an Annual Meeting last year, but I understand that she had to feel she'd be inundated with questions on material she really felt she couldn't yet properly discuss. She's clearly waiting for some success to hold an Annual Meeting, and I suspect it will be for both 2023 and 2024, or just 2024 and ignore that no meeting was held in 2023. Certainly if shareholders had gone to court a meeting could have been forced on the company last year, but the OTC doesn't seem to care, and frankly I'm not sure the bigger exchanges would have if shareholders don't lodge a complaint.
I believe that LP controls enough shares to assure a positive vote on any issue she wishes to raise, but I really believe she'd rather bring up issues that logic says most investors will support and have little opposition. To me, taking on an equity partner, or any type, will require more than the 1.7 billion shares currently authorized. As our share price rises dramatically such a partnership may become possible, that would be when additional shares ought to be requested, so I can't see it being brought up until that occurs.
I look forward to the day when LP, or others from the company, routinely appear at Investors, Brokerage, and Institutional Conferences, but it won't happen until our vaccine has at least UK approval. I believe the company will be very different once that happens and DI has alluded to it in discussions with various posters.
I hope each day isn't a binary event, down if we don't announce approval, up dramatically if we do, but I suppose it's a possibility. If we've had no RFI, we're speaking of under 15 trading days, but if we had a RFI it could be as many as 55 trading days. I really don't believe the UK will provide any hint of when they'll announce, but certainly I could be wrong about that. Practitioners of TA will say there is always a Tell, but if there is, I doubt if many of us will see it, but they'll point to something and say, this is how I knew. Rarely do they announce knowing before an event occurs.
I'll certainly admit that I have no idea what the company intends to do when notified of the UK decision, which I feel about 90% positive about. At minimum, we'll get a PR, but the maximum could be webcasts from the company, and a major campaign in the major media worldwide. That's a very broad spectrum, but anything is possible. Both the FDA and SEC abhor hype, but announcing what truly is a new paradigm in the treatment of brain cancer shouldn't be considered hype if after examination it's true. To add to it, what applies to brain cancers should apply to others isn't a huge stretch. If the media runs with the story, no telling how high the share price could go, but ultimately it will retrench some.
Gary
There is a protocol for releasing data that calls for peer review prior to open discussion of the data, often Phase 1 trial data isn't discussed at all. I would suspect that at an appropriate time the data will be discussed, but this trial wasn't sponsored by the company, so they really won't discuss it at all until after it's been presented in such a forum.
I would hope that it's not long before a Phase 2 that's designated as registrational, or Phase 2/3 Trial is initiated with NWBO being one of the trial sponsors.
I don't believe that TLD statements are normally issued for Phase 1 Trials, or by most trials run at research institutions, but Dr. Liau and others speak at many smaller, and larger presentations where discussing the data could be considered as proper peer review for a Phase 1 Trial. It's not impossible for a Phase 1 that's truly dynamic to be presented at a major conference, like ASCO, but it's doubtful this year as the Abstract would need to have been submitted back in February. Perhaps it would fit into one of the conferences closer to year's end.
Gary
I believe that the odds of getting the UK approval in the coming week should be about 20%. Last week I had it at about 10%, and if it doesn't happen this week next week it will be at least 10% higher, or greater. In three more weeks I still believe the odds go to about 90% but of course if an RFI did come in, it could take somewhat longer.
Personally while I don't remember which poster said no RFI was requested, it's was someone I respect and who I believed was living somewhere in Europe, so they could be in a position to actually know. Of course it also could be a good, or bad guess, but that's why I'm at 90% and not higher.
I'm in L.A. and generally like to sleep until the market's been open a couple hours, but I usually have a quick look when using the bathroom shortly after the open. One day I'll know we got the answer as my account could easily be worth a multiple of what it was previously.
Of course there is also the possibility the company would release news over the weekend, or after the market closed, or perhaps announced holding a webcast prior to the bell, that would be all I'd need to set an alarm and learn what's happening.
Gary
I'm happy that after a few months here you know far more than the company and four regulators they've been working with for well over a decade based on all they've learned during the trial. It's clear that instead of working with the regulators and establishing new goals for the trial when they halted it, so they could end it a few years later, they should have just stopped and taken perhaps another decade or so to get the job done, rather than working with the regulator.
It seems to me that you should be working for the company, perhaps they could just fire all the others and let you take over completely.
Gary
He's no different than most CEO's in that way, most quarterlies are scheduled on or near the last day they're supposed to report. I live in L.A., decades ago most quarterly and other presentations were scheduled about a half hour after the market closed. Suddenly I found most companies switching to an hour or so before the open. I asked my broker what was going on and the explanation was simple, nearly all the Analysts are on the East Coast and nearly all come in well before the bell to get up to date on the news. They complained that when the day ended they wanted to leave, not wait around for nearly two hours to first read the financial, then listen to the quarterly report which followed the release.
While I'm interested, I don't get up at 5 a.m. to see the release, or 5:30 to hear the call, and only rarely am up when the market opens at 6:30 my time. I may use the bathroom about then, so I'll take a glance, but unless I find a big move in one or more of my stocks I just go back to bed until I normally wake up, 1 to 3 hours later. One of these days, if I miss the open, when I do wake up I'll learn I'm half a million or more dollars richer, from NWBO news, I don't own enough AVXL to make that sort of gain, at least not yet.
Gary
Powerwalker, clearly they'll be speaking with a quarterly in the next two weeks, but how much they can reveal above and beyond a normal quarterly may be in others hands. If no material or data that's never been peer reviewed is released, they're limited about what they can say. On the other hand, if they're in control of an issue, like filing with a regulator, they can certainly update about that.
I know that when they discuss million page filings there are companies that specialize in getting them out, just the announcement that such a company has been engaged would be positive news rather than trying to do it all themselves. I'm frankly unsure if even the BP's do it themselves. If they were to announce an intention to file somewhere no later than say the end of the third quarter, it would be greeted positively.
If you're right about discussions with one or more BP's, it would be big news to indicate they're in a quiet period, so it's cannot be discussed. Sometimes the best news available is that we're not free to discuss anything. During such periods they're still required to issue financials, but the failure to say certain things in the financials may be telling a story by itself.
I do suspect that sooner, or later, a BP will either partner, or look to buy the company. Personally I would like the price much higher before it happens, but that can only happen with one or more approvals. Offers very rarely pay more than double the current price, I would hope the company's trading in at least low double digits before considering any offer. Under confidentiality agreements, a potential partner, or buyer, would gain access to all the data we're being denied until it's peer reviewed. That's information that could lead to a much higher offering price, but only after the stock price reflects the news that's not yet been released to investors.
I for one believe that when we get the full story on RETT's we may see a possible path to approval without further trials, but that's purely my opinion. On more than one occasion the regulators have agreed that more than specific goals in a trial should be considered if a product has some benefit where nothing else exists.
Gary
Powerwalker, I'm sure you're right about the company doing the quarterly webcast in a timely way, and yes, they certainly speak with investors whereas NWBO doesn't do such webcasts, so all you get is the written text. As for the Annual Meeting, if Missling gives investors a reason he'd prefer to wait, I believe investors would support it.
Investors want to hear more about the data, until that data's been presented for peer review, the company shouldn't do it. Wouldn't you rather have a Journal out, or peer reviewed presentation first, then have open discussion of the data, or have the meeting and be told that the data won't be discussed until it's been peer reviewed.
I don't believe Missling will delay more than a few months, but I'd rather have a meaningful Annual Meeting in perhaps August or September than a meaningless one in May, June or July.
Another possibility does exist, but only after peer reviewed data's out. Hold a Science Day. It's really just a few hours, but allow the scientists to do far more of the presentation. I don't know them, but hopefully among them there are better presenters than Missling. I know other companies have done Science Days so when the time's right, why not AVXL.
Gary
You're correct, if either NWBO or a contractor decided to build a major new manual production facility here in the US it would be acceptable, but I don't believe they've made that choice. I believe such a facility would cost tens to hundreds of millions and might not be completed before the EDEN was available. If I'm right about biological products not being importable to the US, no matter how much capacity is added at Sawston, it will be of no benefit here in the US.
One large cleanroom with 100 EDEN units would probably cost less than ten individual cleanrooms, each with their own HVAC system to assure no cross contamination between rooms. Even if US approval is delayed substantially, I believe that's the course the company has chosen, probably with the concurrence of CRL who I believe will be contracted for US support, but if they determined to do it themselves, it will be with the EDEN unit.
It's never been about whether it can be done manually, yes it can, but a decision not to do it that way is up to the company and I believe that decision was made some time ago. The company is making and qualifying the EDEN units in Sawston, once it's approved there I believe they'll get little resistance from the US, or anywhere else. I believe that CRL has sufficient cleanroom capacity to operate hundreds of EDEN's or more without requiring new structures to be built in Memphis, they have other facilities that can probably be adapted as well worldwide.
It's rather interesting that shorts are now fighting about US production when previously they indicated that the FDA would never approve the vaccine, that's a refreshing change. I wonder how AdamF feels about it.
Gary
I don't know for certain, but believe that like me, Doc Logic took the change of clinical trials made by the regulators themselves as formal acceptance. If NWBO had pushed for such a change here in the US before the NYAS presentation much of the confusion generated by bashers at that time couldn't have been. We'll never really know if NWBO's submission was very late, or if those responsible for the update were just slow in getting their job done, but of course the submission could have been made well before the conference had they wished to do so.
Frankly I believe that all four regulators have worked close together in this trial, but sadly they all can't just get together on approval. I still believe it's held up for the EDEN here in the US, while it's possible the other regulators, with smaller numbers, may be open to using Sawston with manual manufacturing as meeting at least their initial demands. I could be mistaken, but I believe US laws cannot currently accept products made biologically being made in a foreign country, but I don't think the same applies elsewhere.
Gary
I completely agree with you Chris. Any CEO would prefer to have their Annual Meeting after some good news, rather than when under fire for nothing new happening. On the Nasdaq a CEO probably doesn't have the freedom an OTC stock does, in NWBO's case they didn't have a meeting in 2023 after holding the meeting for 2022 on the last business day of the year, but I suspect that Missling can delay a couple months without a serious penalty. I believe if shareholders wish to force the issue 13 months after the last meeting they can sue, which will take time, but ultimately they can force the meeting, If I were Missling and I expected a Journal publication at any time, I'd wait until I had it unless I had something even bigger to announce, like actually filing for approval.
As for Missling's ability to be CEO, some will deem him a failure right up to the day the company gets it's first approval, then everyone becomes a hero. I believe that CEO's are given entirely too much credit, or blame for what most companies do. If they put together a good mix of the right people, it's all of them that are doing the job. Ultimately it's the science that determines if a product is really approvable, I don't know Missling at all, but I doubt if he contributed much to the science that's produced the company's products.
Sadly, in at least a few companies I've seen good science fail because companies tried to gain approval quickly by using pancreatic cancer as the target for products that worked far better against cancers that took much longer to kill. The company didn't have the funds to do the additional trials so the products were abandoned and the company went belly up. Missling has the company well positioned financially, now the science must prove worthy of approval, I believe that's happening.
Gary
Your fight isn't with me, the peer review publications limit the size and determine the content that they accept, if they wanted that information in, something else would have been out. None of us know what was submitted, included, excluded. Had it been up to me, a simple statement would have been made about progression not working for this trial, and everything else about it left out, but that's not how they saw it.
As for what you said about the SAP, both the UK and Europeans changed their versions of Clinical Trials after the halt and acceptance of what the company proposed, that's as close to acceptance as you'll ever get, the company was actually surprised that they made the change.
Many things the regulators do are not formally accepted, if you submit a change or make certain submissions and nothing requesting changes in a specific amount of time is returned, your submission is presumed to have been accepted. It actually all begins with an IND to initiate a trial, no formal document accepting it occurs.
It's very common for shorts to ask for documents that don't exist, you know they don't exist, but asking for them creates doubt, and that's what bashers are all about. Approvals are the answer to everything and I don't believe it will be that much longer before we have at least the UK saying yes.
Gary
As a reasonably new investor in AVXL I've seen a great deal of criticism of the CEO, but honestly it's nothing that I haven't seen in other biotechs, and in most cases it's been for the same reasons. In most cases it's because investors believe that once a trial end, they're entitled to in depth trial data. In reality, the company does give Top Line Data, but that's just a paragraph or two summarizing what's seen in the trial, after that, once data's been peer reviewed and presented, then they can talk about it.
Sadly, companies want the peer review to be done by organizations deemed to be highly respected, and they'll wait for them rather than finding the first conference or Journal willing to permit a presentation. I'm much more familiar with Oncological products, and there conferences like ASCO are where they want to be. I'm sure much the same applies here, though I don't really know the key conferences, or publications they're working to get into. My point is, it often takes many months, sometimes in excess of a year to get the data presented in the manner they wish it to be, and until that happens they simply would be violating proper protocol to discuss them beyond what's in that TLD statement.
When a peer reviewed presentation is made it won't be just the positives, it will be a review that has positives, negatives, questions, etc. seen in the trial, it's rare that nothing negative can be found. Peer review will cite both good and bad, that's what it's all about. Competitors, who fear approval of a competing products may have their own "experts" develop presentations that counter the good as well, money will buy almost anything, and some lessor publications or conferences will accept what's provided and consider it peer reviewed by their staff.
Finally there are the geniuses like AdamF, with his degree in PoliSci, as I remember it, that work in support of shorts to put down companies who put their spin on the results, and sadly many people do follow them, as well as the hedge funds that no doubt employ them.
In time, all of this becomes meaningless if the company applies for approval with the regulators, and gets it. When revenue builds, that's something that can't be denied, but until that happens, one minute the CEO's terrible, the next he's brilliant, it's all dependent on the current stock price.
Gary
Dstock,
I know there has been a lot of talk about synergies with RevImmune, as well as Advent, which LP has control of. As I see it, it's up to her whether it's to both her best interest, as well as shareholders, to act on what she's clearly in control of. Clearly whether she does act, or allows things to continue as is, her holdings are so great that effectively she has control of all three companies.
My thinking would be, she won't do anything prior to much higher prices for NWBO, and at that time if she acts it not only may combine all three, but to add a fourth, the developer of Poly-ICLC. When I invested 5 years ago the thinking was NWBO would eventually be bought out, that may still be the plan, but another possibility may be developing to make NWBO, or something with a new corporate name that includes all the above, into a greater sized biotech. With some success, anything is possible.
While I'm still of the belief that CRL will be part of the plan for the production, storage and distribution of the vaccine in much of the world, it's not impossible that LP will look to acquire production capability rather than contracting for it. It's clear that LP has substantial financial resources, or knows where she can get them, so nothing is out of the realm of possibilities, but it all starts with approval of DCVax-L and the EDEN unit for making it.
Gary
LC,
In reply to your multiple posts, first I believe that most if not all in the control had real progression, not pseudoprogression, but regardless, at that point all were permitted to cross over. I believe the reason that many chose not to cross over was that their conditions were so bad that they resigned themselves to die. As for the data, the JAMA publication does what the peer reviewers permitted to present it. I don't know if the presentation would have been substantially different if peer review were different, as I stated, benefits would have been much more clearly made if all mention of progression was eliminated as some progression was truly progression and some was pseudoprogression, but no real attempt was made to differentiate one from the other.
I believe new trials will not have control groups, even if pseudoprogression can be differentiated from progression. The FDA has clearly in their Journal publication has been open to using historical information rather than control groups when it comes to terminal diseases. I suppose it will be up to the trial sponsor, but I believe in any trial NWBO runs all patients in the trial will get the vaccine from the beginning and the comparisons will be drawn against historical information. Ultimately I believe most companies will opt to design their trials this way. No doubt placebo's do make differences in some diseases, but in deadly disease long term they make little difference in overall survival, but perhaps more when it comes to determining progression. In reality, the FDA has found that some products approved on PFS are not really improving on OS, but they remain approved as they clearly give Drs. more choices and they're not doing harm.
I believe the more options Drs. have the longer patients can survive, not because one is necessarily better than another, but rather because as a patients becoming refractory to one, a Dr. can switch, they can alternate many times rather than allowing the cancer to become refractory to the treatment the patient is on. I can't say if a cure can be obtained this way, or not, but years can be added and if products like DCVax-L are helping to add the years it will be at high qualities of life.
I've spent time on the oncology floor of a major hospital where certain patients lives may be extended, but they never left their rooms, and probably never got out of bed, it's not much of a way of living. I was fortunate enough to never be in that state, though at times I was isolated to my room, but at minimum could walk within it. I actually met the wife of someone I hadn't seen for years who was there to visit her husband, I couldn't visit as he was isolated, and after I left did pass on. Quality of life really is an important issue and I believe that in virtually all cases, our vaccine will not adversely effect quality of life and may help to eliminate the need for certain other products that may have benefits, but have terrible side effects while on them. Cancer itself my offer a terrible quality of life, but many of our treatments for it make it substantially worse, our vaccine has virtually no negative side effects and may in fact make the quality of life far better, especially if it's use ultimately yields a cure. A failure to approve it would really represent a failure in the system, not the vaccine, as its approval would not be denied, only delayed. I've seen many blockbuster drugs that were delayed by the regulators, and sadly it's the patients that could have used them who were denied, their success was delayed.
Gary
I had not heard of NWBO decades ago when the trials began with DCVax-L. As I understand it a Phase 2 essentially morphed into a Phase 3 and while it was a blinded trial, what was learned during the trial couldn't be blinded, for if it was, the trial would almost certainly be abandoned. What was being seen in the trial was patients deemed to have progressed, but in spite of being deemed to progress, they were living longer and their health improving. This was determined to be pseudoprogression.
The result of what was being seen ultimately led to a temporary halt in the trials, and during that halt the trial, still blind to the company in terms of details, was redesigned in terms of utilizing what was learned about pseudoprogression to properly evaluate what was happening in the trial. If the trial had been simplified to what mattered, all references to progression would have been eliminated, all that should have mattered was overall survival, but it wasn't that simply redefined. The analysis of progression remained within the trial, even though it was known that many who received the vaccine initially were judged to have progressed quickly, because it was actually pseudoprogression, while those in the control were living longer before the determination of progression. The K-M plots gave the appearance of those on placebo doing better than those on the vaccine.
If all this data had simply been ignored, the likes of AdamF and many other shorts wouldn't have a leg to stand on in discussing the trial, but it wasn't. Many have successfully called the trial a failure based on the K-M's which are based on PFS showing those getting the vaccine were deemed to progress before those in the control. Thankfully the regulators understood what was happening and accepted the redesign of the trial after the halt, but they didn't completely remove all discussion of progression, so it remained a target for all trying to put down the vaccine.
Presentations may have documented what pseudoprogression is well, but things like the misleading K-M plots remained in what was being reported and therefore remained a target for criticism. I certainly don't know, but suspect that if we looked at many of the longest living patients we'd find that many had been found to progress very shortly after treatment with the vaccine began, while as a whole, nearly all who purely stayed on the control, never getting the vaccine had passed on among the earliest to do so. The good news was for some in the control who progressed, treatment with the vaccine did help, but it was clearly seen that none should wait for progression to be treated and after the halt, all received the vaccine immediately.
If knowing what's known now a new trial was designed, from the beginning it would have no control, but likewise, knowing what's been happening at UCLA they'd add Poly-ICLC and/or Keytruda and take survival to somewhere over 50% at 5 years. A 5 year trial shouldn't be needed, perhaps 70 to 90% would be alive at 2 or 3 years, certainly enough to make an approval determination, but hopefully the regulators can act without waiting for such proof. They may not put Poly-ICLC and/or Keytruda into the approved protocol, but encourage its use regardless.
Gary
I'm certainly no expert, but I suspect that many of those pages are generated as a product works its way from preclinical development through clinical trials. They essentially provide the backup to significantly fewer pages that are the real guts of the filing. On the 1.7 million pages in the NWBO filing almost everyone I discussed it with agreed that less than 10% will probably see the light of day.
Gary
While it would be great to learn that the King, or any other major newsmaker, was getting DCVax-L for what would be considered an off label use, it's not nearly as important as the UK regulators saying we have an approval.
In the past celebrities often haven't seemed to have gotten the best treatments, at least not when it comes to taking experimental products. If they do, it's generally not until the SOC treatment is clearly seen to be failing. No doubt they get some of the finest physicians, but not necessarily the ones doing a great deal of experimental work. I doubt if the treatment protocols for most celebrity treatment is ever made public, whether successful, or not.
Gary
Just a thought on the RFI issue at the company. While I believe that there is a good chance that no such request was made, if it was, it's not something that people like DI or others involved with the investment public would be permitted to discuss, so it would be my contention that they would never be told. I would suspect that the only ones to learn of a RFI from the company would be those given the responsibility of answering it, and very probably those on the BOD. Of course it's already very possible one or more contractor could be involved.
I believe may are developing a course of action once the outcome is known, but if they're not involved in responding to a RFI, they won't know if the company was ever asked.
Gary
If I were the company and expected something positive, like a Journal or regulatory filing in the near future, I would not call an Annual Meeting until I knew that it had happened or was about to. It should be within 13 months of the last meeting, but the regulators really don't seem to care, so if shareholders don't force the issue by suing, they can do what they wish.
Gary
I wish the German Col the best in what he's purchased with proceeds from the NWBO he's sold, but I believe that it's what he retained that will make him the greater gain, and it won't be much longer.
I got to thinking about all the people I've suggested NWBO to who bought, I really don't know how many shares each one purchased, but I'm certain the total holdings on my part and those who've joined me is well in excess of half a million, but I don't know how close we could be to the one million mark.
I really don't believe the UK regulators will wait for the entire 150 day period, but while reliable posters don't believe an RFI came in, I don't think we can be absolutely certain. I think we can be certain the company wouldn't PR an RFI. If I'm right we have less than a month before we know.
For anyone who also looks at I-V, I'm happy to say it's back up and hope they can keep it that way. Most there are shorts, but largely intelligent ones, and some I respect, even if we don't agree, but we do have some longs there as well.
Gary
Newman, the question I might have is if DCVax-L is approved and a patient has unlimited funds, would any oncologist recommend using both the vaccine and the helmet, and of course Keytruda and or Poly ICLC.
Gary
That is simple, LP has set a price point that they would be considered to be insane to meet until the share price is near half that price.
Gary
I believe that the company, and Drs. primarily in the UK have enough tumors in storage and patients lined up to keep their limited production capacity working for some time. Once word of the approval is out, this will grow dramatically without a major sales or advertising program. Furthermore, we know the company has contracted for all sorts of things, I still believe that both Advent and CRL will be involved in the commercial production, storage and distribution of the vaccine, if there is a need to line up more patients, because they have the capacity, perhaps that too will be their responsibility.
Of course Advent and CRL will do well in this arrangement, but so will NWBO, they'd have almost no added expenses, but would be collecting for every patient being treated with the vaccine. As I see it, it could be a very win-win proposition for all concerned.
Gary
Remember, they are going for the UK first. They have Advent setup to do what is needed there, no need for a major staffing growth. If even in the US they choose CRL to function in a similar capacity, they could do it without major staffing increases.
The company has used contracts to get this far, what makes you think that now they will do things themselves.
Gary
Jester, I'm not saying that at all, it's purely a coincidence but if the 150 day period applies, the approval should come in before ASCO, if there are delays, it could happen during or after ASCO. I'm sure the submission wasn't intentionally timed this way, they planned to do the submission over a month earlier. If they do have the approval by ASCO I'm sure that both their booth and Expert's Theater presentation will reflect it.
My timing is no different from others here, I just brought up the point that it could tie in nicely to ASCO.
Gary