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As always, thanks for letting us know.
It is painful to watch the stock price drop. I won't deny that. I do agree with you that the dilution really should not mean much. There are just too many possible catalysts that could potentially occur at any time. I also believe like you, that mesenchymal subgroup approval is being considered. That would change things overnight. The possible partnership depending on the terms could also be a powerful catalyst. When Celgene partnered with JUNO the share price of JUNO went up as much as $29($40 to $69). Something has gotta give soon. I appreciate your posts which help me keep my attitude positive in moments of weakness. Best of luck:)
I bought 292 2018 $5 leaps. Trying to accumalate shares. Hate what I am seeing, but really believe all will end up well. GL longs.
Is the extension 15 days?
That is a great catch, you may be right. My belief in vaccine therapy for cancer started when I was a fellow. The work being done with whole cell vaccines on melanoma made me a believer in the potential of the vaccine approach. I have seen the potency and effects of the main modes of immunotherapy throughout my career(e.g. antibody, adaptive T cell, BCG, cytokines, & vaccines). BCG is fairly weak and of limited use on it's own. Cytokine treatments can make you so sick they can require hospitalization during treatment with very limited overall survival effect. Adaptive T cell treatment at this point has a questionable role in solid tumors. Antibody treatment such as PD-1 and CTLA-4 are effective to a degree on their own but are quite toxic. I can tell you first hand more toxic in person to most than is discussed in the literature. Response rates as single agents are fairly low, abour 20%,. Also realize, that of those 20% that respond, half of those patients only get a few extra months and half of those patients are miserable(gives you an idea how much room for improvement there is). Combining of antibodies is even more toxic, quite miserable to see in person actually. Yes, you get a nice response rate, I think aroud 50%, but up to half of those can't complete/continue treatment. Also a lot who are able stay on treatment feel like crap on a good day. The "crude" vaccines I saw for melanoma had almost no side effect. Those that responded had disappearance of multiple "bulky" tumors and sustained responses in many cases. Unfortunately, response rates were just too low for the early vaccines. I am fully cofident as more is learned the vaccine approach will be the future of treatment. If not on it's own, atleast part of a "cocktail". Time has taught us that mesenchymal tumors are the most immunogenic. Such cancers with the epithelial-mesenchymal transition include melanoma, non small cell of the lung, colorectal, GBM and prostate. There is every reason to believe that these cancers can be treated with "L" and the hope of an improvent of PFS and OS. The data that we are aware of for mesenchymal glioblastoma helps support this hypothesis. Some of the cancers I have listed, even when removed in surgery for "cure", have very high recurrence rates. Antibody treatment such as PD-1 have or will most likely have an effect on the cancers I mentioned, but in the overall picture it is limited. DCVax has the potential increase those effects, making it attractive to those drug makers. In the case of tumors that are clinically removed, "L" could handle the low volume residual disease that causes the recurrence in those patients. This knowing that the potency of "L" would most likely require lower volume disease to be successful.
Anyways, starting ramble on. It is just hard for me to get in all my thoughts in a short post. I know I am a horrible writer. Just saying I agree with your thoughts and some of the reasons. My hope is that "L" gets some type of approval for mesenchymal GBM in the very near future and the trials for "L" in some of these other cancers(or sarcoma) start soon. Hoping for arms using "L" alone and in combination with different types of antibody treatment.. Hope that is a reasonable wish?
Thx for responding, I did not think of that scenario.
Woodford Patient Capital Trust has been doing well lately. It is almost even now after some significant loss. Wondering if this may allow him to be more aggressive with NWBO if we get a clean investigation here within the next few weeks?
The data generally shows that PD-1 blockers show longer survival times and less side effect than ipilumimab(ipi). The reason is because they work at different stages of T-cell maturation. Ipi works on more immature T-cells(in lymph nodes) and allows for their uninhibited proliferation. PD-1 blockers take effect on T-cells that have already matured and been actvated by keeping them "on". Since ipi works at a more immature stage of T -cell development the side effects will be greater by creating excessive T -cell that are not tumor specific and create an "autoimmune phenomenon." PD-1 should do less of this because it is not really increasing the number of T-cells. It is just not allowing the tumor to turn off cells that are already there.
I would think in general ipi would be less effective with DCvax because not only will the PD-1 pathway be intact it will be amplified due to DCVax allowing the activated T-cells to be "shut off."
In theory, DCvax could be thought of as giving ipi without the side effects. It is increasing the number of tumor specific antigens(neo-antigens) without increasing the self antigens(autoimmune phenomenon). Adding PD-1 will keep them "turned on". You are essentially getting the ipi/PD-1 combination treatment with much less side effect and in my opinion because of the highr tumor specific antigen(neo-antigen) production by DCVax and more patients being able to complete treatment the probability of even be a better results.
I just can't believe with these possibilities the share price is where it is. Quite frankly, I am shocked. This science is the most potentially disruptive I have seen when it comes to cancer in my career.
One possibility considering cost would be to ramp up the immune system with PD-1 blocker and then switch to DCVax. Studies will show what would work best e.g. combination with both at the same time for the whole treatment, overlapping treatments, or one after the other. A lot of good things are hopefully on the horizon. I am sure cost will be an issue though.
The epithelial-mesechymal transition is a very important characteristic of many tumor types(e.g. melanoma, lung, pancreatic.....). It is associated with metastatic potential, resistance to conventional chemotherapy, and inhibition of the immune sysytem. This creates an oppurtunity for the use of immunotherapy. Certain receptors such as PDL-1 are upregulated in many with these changes. This is part of the reason we are seeing such a broad effect with PD-1/PDL-1 inhibitors and preliminarily with DCVax direct. I am really looking forward to news and possible combination treatment using Direct with PD-1/PDL-1 inhibitors.
Sorry, I meant epithelial to mesenchymal transition, not epidermal. The terms can get cofusing.
I agree that CXCR4 is important. Multiple different sources have shown that this is an important pathway that allows for metastases, infiltration, angiogenesis, and tumor cell survival. It has made it's way form work done in HIV to lymphatic cancers and now to solid tumors. The most published work seems to be in breast but over 20 other solid cancers have shown some relationship (e.g. pancreatic and lung). It will be interesting to see what blockers of this pathway will do. What I mean is what there response rates will be. It depends on where it lies in the web of overlapping pathways that allow cancers to either not respond or escape treatment. What about in combination with other treatments? Anyways, it will be interesting to see what is happening behind closed doors.
My feeling for what it's worth is that the long delay in L is due to subgroup analysis. Speaking with some people who have had experience with DCVax and what I know about mesenchymal tumors in general has lead me to think this. Mesenchymal tumors in general are immunogenic. Tumors like melanoma that go through and epidermal to mesenchymal transition are of the most immunogenic tumors known. That is why they respond so well to immunotherapy. In melanoma it is not unusual to see primary tumors/or metastases even resolve without treatment. Inject BCG in an in-transit melanoma metastases and the intense immune reaction will cause it to undergo necrosis. I believe that this response to immunotherapy will translate into superior results not only for the mesenchymal subgroup of GBM, but also for pseudoprogressors and recurrent GBM. Reasons like this are why I believe so much in the potential of L on glioblastoma. Also I have spoken to a few neurosurgeons during the time I have been invested. I have heard them say that they believe certain subgroups will benefit significantly from the addition of immunotherapy to their treatment. I really won't go into more detail. JMHO
I would be in.
Thx Dan88
I am very confident the mesenchymal subgroup data is going to be excellent. The question I have to anyone who understands the statistics in this trial well. Is there enough power in the trial, the way it is, to show enough statistical significance in this subgroup to get some type of approval?
Could they use data from the information arm or expanded access to help with this type of decision?
Thx for looking that up. Sorry, I think I must have remembered it the way I wanted to. One thing for sure, you apply for AA before trial completion. That is part of the definition. Thx for letting me know Beartrap is a women.
Not 100% sure but I think that someone asked at the shareholders meeting(maybe Beartrap) if they were going to apply for AA. Linda I believe responded by saying that they cannot apply for AA until enrollment is complete. I would think if the DMC has recommended a review of data in some way things might be different. I did not try yet and look back at Beartrap's posts, I mention him so someone with a subscription may be able to look up the relevant posts easier.
Does it not make any sense to do a financing deal before the news since the price is so low already? We have not dropped in SP all that much. It may have have had a greater negative effect at a higher share price, no? Now once they give good news(hopefully), they will not have to do another financing to stop any positive momentum, considering there are multiple positive catalysts out there that could occur soon?
Not trying to challenge you, just trying to learn. I hope others will chip in with their opinion as well.
Glad to see someone is up. I really felt blindsided by the financing today. I have to admit I never really saw this as their next PR. Anyways, I would think the best thing that could happen next would be for the investigation to be completed and for no wrongdoing to be found. Which I believe will be the case. If this is done first, then when the L trial starts screening again or if we get some type of approval the effect would be much greater in my opinion. Not only some new buyers but Woodford may start accumilating again, driving the price up more effectively. Hopefully we hear in the next few weeks.
With this kind of news I would have thought the price would have dove more and that the volume would be much higher. Any thoughts?
Looks like another update on clincaltrials.gov yesterday. University of Texas, San Antonio. Don't know if it is another new location or just updated info. Strong addition if it is new.
Thx, TC trader
How many shares does Cognate have at this time? The institutional numbers are pretty much updated on NASDAQ so i am just trying to calculate how many shares are tied up. Also it does not look like those institurional numbers on NASDAQ include the stock of Dennis Mehiel and his wife, is that right?
The amount of relentless effort to discredit a company that no one is really paying much attention to in the first place is just amazing to me. Never seen anything like it really. The stock is already below 2 dollars. I am beyond heavily invested and I don't take the time to refute most all of what I think is just negative speculation. Just don't have the time. It is not to hard for me to see gaping holes in most all of the negatve post without too much thought. I add that on to the amount of effort to destroy a company that is nearly financially worthless in the first place makes me believe in the science more. With the effort that is being put in to destroy/smear the company you would think there were tens of billions of dollars at stake. My guess is that worth is sitting in the form of positive data that really scares the crap out some people out there. You don't need to know any science to see that. JMHO
Koman,
When a it comes to the injection causing the necrosis, that is not possible in my opinion. I personally have ablated tumors with electric current, microwaves, and alcohol. The small amount in the DCVax injection could not do it from my clinical standpoint. In my opinion, impossible, the injection is too small. I do not even have the slightest concern that is happening.
I cannot prove that your predicted outcome for the trial will not happen. If I Could, I would be pretty rich already. Likewise you have not said anything,, nor has anyone else, with the minimal treatment(# doses, amount per dose, tumors injected) that it will not increase survival by at least "stretching out" life. This by stunting growth of potentially fatal enlarging primary or metastatic tumors, converting patients to operable, or even curing a smaller number of patients. Yervoy can have an wffect on melanoma in a similar fashion..
I think they are on to something and the technology will continue to get better. You don't think it is ggod enough, I think it might be. I agree to disagree. Anyways, right now I am concerned about "L"., as most investors should be right now. I think that is looking pretty good.
Thx
Hi Jack,
For what it is worth I will tell you WHAT I THINK. The arguments of the negative posters on this board continue to not phase my confidence in the least bit. I really don't have the time to refute everything that is said but as someone who deals with this everyday i read one of these negative posts and It just makes me roll my eyes. I can only equate it to having a medical student in the OR with me. They can recite the whole procedure from beginning to end better than me. The problem is if I left them alone the patient would most definitely be dead before they left the OR.
I will give you an example from today on the board. I will talk about necrosis. Necrosis in itself is good. It means those cells are dead. There is no blood supply to that area. No discussion. When can seeing necrosis in another setting be bad? Someone comes in to see me with abdominal pain. He has lost weight and has a poor appetite. I get a CT scan. I see a 10 cm tumor in the bowel and it has 50% necrosis. That is a really bad sign to me. The patient has never been treated, has a tumor that is growing so fast that it is out growing it's blood supply. That tells me two things off the top of my head. If you give chemo it will probably melt away pretty quickly giving the patient and family a false sense of hope, because the imaging will look better soon after treatment starts. The problem is if the cells are dividing fast you get more mutations occuring, the chance of resistant clones surviving, being able to escape, get new blood supply, evade the immune sysrem, and grow in new sites is greater. Probably more aggressive than the first tumor. I can usually infer this possibility when you tell me the tumor type, detailed biopsy results, history of the patient, and imaging. Gosh, I could write a lot more but you get the idea. In this case seeing necrosis is a bad sign. NOT THE NECROSIS ITSELF. I think DCVax would actually help in this case. The only thing that I know of in the world that could keep up with a tumor like that is our own immune system. What could help to bide some time while the immune system ramps up, maybe a checpoint inhibitor?
Another REAL LIFE example where when necrosis is present a tumor may grow is in the treatment of liver tumors. Patient has a large tumor in the right liver. You cannot talke it out because if you remove the right liver there is not enough left liver to survive. So you embolize the right liver(cut off it's blood supply). After about 6 weeks you see necrosis of the right sided tumor and the left liver has grown 50% to compensate for the loss of the functional right liver. Now you can remove the right liver. Sounds great. There is a potential problem. If the tumor is large or was large on the right(with or without necosis before cutting off it's blood supply)then there is a pretty high percentage chance there was microscopic disease on the left. Well we just gave that microscopic disease growth factors and more boold supply on a silver platter, whoops. Just took out half a patients liver and 2 months later they now have 5 tumors on the remaining liver. The odds of this are different with different kinds of tumors and different even with same types of cancers. It becomes even more complicated when you factor in chemo. Again I could talk for hours about this. It is a complicated spider web.
I see no situation that the necrosis that DCVAx could potentially produce would be a probem. Necrosis in itself seperate from any treatment maybe a "sign of traetment outcome before treatment, a good or bad sign after treatment. If it is a negative thing it is because of the biology of the tumor. If it is a positive thing it is because of treatment. Personalized treatment with multiple attackable antigens, and immune memory is the answer period. I BELIEVE nothing is even in the same universe a the science behind DCVax. I know it works, the question none of us know, does it have a decent enough respose rate? Is the effect reproducible enough with the tecnology we have now to get approved. The technology will improve, the sky is the limt here. We who believe hope that NWBO is the foundation.
To The longs, the negative on this board especially recently is just complete BS in MY OPINION. Does not shake my confidence one iota. I am in until we know. I think it is gonna be pretty darn soon.
Hope i helped some of you understand things you may have not before. GLTU
Data from MD anderson in 2002. I think it can be fair to add even 1 to 2.5 months on to PFS/OS if improved imaging has increased the amount of 99-100% resections or at least made them more legitimate:
85% resection median survival 10.9 months
90% resection median survival 11.43 months
94% resection median survival 11.9 months
96% resection median survival 13.1 months
98% resection median survival 13.4 months
100% resection median survival 13.6 months
A have read literature that has said getting less that 92-93% of the tumor provides no survival benefit over palliative chemoradiation. Palliative chemoradiation can have survival anywhere from 8-14 months depending again on who you believe. Progression free survival once starting treatment is about 5-5.1 months. Remember patients that get palliative chenmoradiation are strong enough to handle that tough treatment. They are not the patients that are die or are expected to diet in a month or 2. This is part of my argument in why I do not think the STUPP protocol is too far off. The point again is that the difference between surgery and biopsy without adjuvant treatment just is not that much according to most institutions. Numbers may be a little higher as a baseline in the DCVax L phase 3 study but if the treatment works it really should not confound the PFS results.
Does it work, none of us really know. Again no argument has made me believe that it won't. Nothing else out there I have seen or read about in my opinion has better chance of working.
I agree, surgery does matter. I am saying there are a lot of good surgeons. Just because you can see the disease on the MRI does not mean it can be removed. Even then rarely is a margin taken(problem we run into with sarcoma and pancreatic cancer). Also the difference in survival historically between biopsy only and resection without chemoradiation is around 1.7 months. Significant but not too impressive. So I think most survival is coming from the adjuvant in that study. This is MY OPINION. I felt I needed to put it out there.
I am sorry about your nephew. I know this must be a bit personal when it comes to the truth wether the treatment works or not.
I will try and give you MY OPINION on one topic about the trial that is being beaten to death that I think is ridiculous. Some posters are saying that the crossover to DCVax after progression on placebo will be areason the trial will fail. I did not even think about this as a concern. Every cancer has a different biology. GBM is not like breast cancer or colon cancer. Many patients with breast or colon cancer recurrence/progression can live for years. It is not unusual to see breast cancer patients with bone mets live well for ten years with no treatent or just anti estrogen therapy. Lung mets ftom colon cancer can be fatal in weeks if there is lymphangietic spread or years is there are only a few spots(sometimes you can operate on them as well). I have a patient with lung mets I sat on for 1 year just watching, no chemo . She did not develop new lesions and the three she had were growing so slowly we thought we could "reset" her clock. She is still clinically free of disease 6 months out qnd off chemo. There is such variability in the diseases I mentioned that a crossover after progression might make overall survival difficult to interperate and comparing to natural history would be less valid. GBM is more like pancreatic cancer. Once you recur, survival is fairly consistent for the majority of patients, it's terrible. Yes, there are the few who can have a re- resection or respond to second line treatment but not that many. It is a no brainer if overall survival after progression is 12 months(WITH NO SIDE EFFECTS) it means something if they got DCXax. That just does not happen consistently. If a doctor I worked with told me that it did not, i would never refer to him, that is for sure. On top of that we may be talking about patients who progess on DCVax after even a longer time than patients historically live. And there is a control group for progression taking into account the SPECIFIC issue with GBM in that the different subtypes recur at different times. With mutations that occur in recurrent GBM survivals are more consistent without treatment or response to it. It gets awfully complicated when you start factoring even more like MGMT staus and EGFR status. I personally think the data will most likely show an effect in the mesenchymal subtype(hopefully all) because it is the most immunogenic(like melanoma is). The conversation about proneural can also get complex. Yes, it has a longer time historically to recurrence but the revurrence may respond to DCVax if it has transformed to a mesenchymal subtype(hence a second line treatment for recurrent proneural.).OK, I think I will stop.
Again I will say don't let the BS shake your confidence. Immunotherapy is the future. I hope DCVax is the start for patients and longs.:)
This is the kind of stuff that drives me nuts. I did my fellowship in surgonc with the UCLA surgeons. I practiced in San Francisco for 9 years. Worked with multiple specialists at UCSF. I agree with you 100%. The surgeons are not better at UCLA than UCSF or vis versa. The survival at UCSF is about 15 months. The technology does not make that big a dent, period. I know, I am around it all the time. The difference in survival between a 98% removal and a 99% removal are going to be minor, no one would say that to a patient but that's the reality. It is the adjuvant treatment response that determines survival in these types of cancers. I am pretyy busy right now so I can't go on. When I read some of the discussion on this board about surgery like the recent post by RK it is just such BS from someone who has no clue what they are talking about I just had to write something. For those who believe in the science, I just don't want you to lose faith for the wrong reasons.
For those who are continuing to hold on tight like me, here is something I looked up that helped me relax tonight:
Dendreon in March of 2009-$2.61
June of 2009-$26.00
March of 2010-$38.00
I think NWBO differs in trend after this amount of time because of a superior product, more efficient manufacturing, already existing international infrastructure with caregivers already trained throughout North America and Europe. I would not be surprised if the the share price trend shown above is more dramatic for NWBO. With all the potential applications alone or in combination, significant short interest, low number of truly "free" shares, and the possibility of a significant "naked" short pool the imagination can run a little wild. Anyways, just trying to be patient and stop getting too high or too low.
Well if you were choosing a knockout punch, could not think of a better one.
Could the 26th finally be the time to announce a combination trial with a check point inhibitor? Looking at the presentations it seems to be a hot topic. A decent amount of financing from the CI partner would also be nice. That may be enough to initiate a nice share price upswing.
If Woodford really wanted to just lower his position so he can derisk, why not just sell the shares he bought on the open market? That would seem like the best way to keep suspicion low and get the most for his shares. What he did just does not make sense if he is looking to get out, even a little. It actually makes more sense that he is trying to psych the shorts out. Make them think that he is freeing up shares for upcoming "good news". I would not be terribly surprised to even see the price creep up in anticipation of good news in the next few days. Though I think more likely we just get a healthy spike with some good news down the road nearer to the conference.
In trying to put a positive spin on this. Could he be making these shares available in the possibility that there is good news on the horizon? Were these shares restricted from being sold before this?
Hi TC,
Wanted you to know I appreaciate your help to the board about explaining things from the stock market perspective. I remember a post you wrote a ways back about what you have done and why in terms of investment in this stock. I felt like I was reading my own post. I hope that my investment will help me have more control of my life, be there for my family like I have not been for many years, and let me use the skills I have developed over the years for charity. I don't bother trying to pull out papers that will refute what is said negatively on this board. I just don't know how certain people have that much time uless they can spend countless hours a day doing it. I have done clinical reasearch, I know it takes hours and hours everyday. Anyways, for every paper that I find positive, there is a paper out there that is negative that will be put up to refute what I post. Anyone who knows research knows that is the case. I personally have a hard time believing anyone who is too certain they are right about there position. I have a really hard time around arrogance. In my field I see people die directly from it. I made my choice, I am in until results come back. I may loose it all. Like you I am still young, and my kids are young. I can work hard and make up for it. I hope that is not the case but I, along with the blessing of my wife, took the risk. Please keep posting, it really does help some of us, hope we can celebrate success for those who suffer from cancer and for our families some day soon. On call, gotta get back to the OR. Have a good night.
I do not see it the way you do. With DCVax brain you are not trying to kill an adult Rhino, you are trying to kill a baby rhino. Most, if not all of the gross tumor has been resected. There is a very small amount of disease. The goal of the vaccine is of course cure but a significant increase in progression free survival, which most of us will agree in this particular cancer will translate to an increased overal survival, is a huge victory. On top of that doing it without any debilitating symptoms. I think people can be so close minded or black and white about a treatment. I believe the initial success with dendritic therapy will be converting a terminal disease to a more chronic type disease. Much like diabetes. Some people have complications of diabetes and die in a few years. So many factors come into play e.g. Severity of glucose intolerece, underlying health, compliance and so on. Some patients diabetes is easily managed and they live long lives. People will react differently to dendritic cell activation. Some will have a more intense initial immune reaction, some will create more immune memory, some will have tumors with expression of more or less factors causing immune suppression. This leads to the results we are seeing. A significant number of patients with longer than historical progression free survival and the more than historical number of "cures". As more about the immune system is learned, the potency of dendritic cells will improve(they may have already done this)., optimal doses are learned, combo treatments are created I believe cure is a possibility in the future. I can give you a whole other theory on direct but I am too tired. I know I can't convince you. Heck, I might be wrong on this company, I am not arrogant enough to act so sure like some that can be so sure this company is going to fail. I have said before this is the right path, targeted immunotherapy will have definite barriers in solid tumors in having high response rates. Anyone who has a basic understanding would never argue that. You can only combine so many toxic drugs to get a good response rate and let's never forget about quality of life. I really think people are scared. I am a surgical oncologist and a busy one, meaning I have seen a lot of disease treated. THIS IS DISRUPTIVE if it works.. I think a lot of people want to slow this company down to protect their piece of the pie or get there first. This next statement you can chose to believe or not. I have a good friend who works for Genentech. He told me that no one is as far along in dendritic cell therapy. He used the phrase "not even close".
To all the longs/believers I wrote this more for you in this quiet time. Don't be fooled by what I think are close minded arguments by the doubters. I see nothing Out there that puts any doubt in my mind that success is highly possible. It will feel awesome to be a part of it, should it succeed.
Tough question. In some people you may be right depending on what is the main factor creating their problems. Not every pt with a hiatal hernia has reflux or esophagitis. There is though a physiologic/anatomic change in the sphincter mechanism due to the amount of inta-abdominal esophagus. Fixing this with surgery may be the only way to prevent Barrett's esophagitis and cancer. Is it acid reflux or biliary reflux? Too many factors for one definite answer. Diet change by avoiding certain foods, timing of meals, antacid therapy, prokinetics should be first line treatment. Surgery does not fix everyone. In pancreatic cancer we just fail way more than we succeed. A 5% 5 year survival(80% inoperable, of those who get a Whipple 20% 5 year survival). The only thing that is going to fix that is better systemic treatment, that is what I was trying to say.
over 200, don't really enjoy doing them anymore because of such a difficult recovery and poor long term prognosis. I feel it really is not a surgical disease even though we treat it like it is.