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  • ImmunoCellular: Post Hoc Analysis Of Disappointing Phase II Trial Of ICT-107 [View article]
    Perceptive as usual.
    Dec 16 04:51 PM | 2 Likes Like |Link to Comment
  • ImmunoCellular: Post Hoc Analysis Of Disappointing Phase II Trial Of ICT-107 [View article]
    The data is quite encouraging based on what I have seen. It appears to be as good or better than the data on which Avastin was approved in recurrent glioblastoma. I am putting together a note.
    Dec 16 10:21 AM | 1 Like Like |Link to Comment
  • ImmunoCellular: Post Hoc Analysis Of Disappointing Phase II Trial Of ICT-107 [View article]
    These were not newly diagnosed. They were recurrent glioblastoma patients. I have only looked at the press release at this point.

    Avastin was approved in recurrent glioblastoma partially on the basis a trial in 48 patients that showed that 57% of patients were alive at six months (CI 44% to 75%), and that median overall survival was 31 weeks (CI 21 weeks to 54 weeks).

    I have only looked at the press release so far that states that in 41 patients 90% of Prophage patients were alive at six months and 30% at one year. Based on this extremely limited information, Prophage appears to be having a clinical effect that the FDA considered meaningful in the case of Avastin.
    Dec 16 09:51 AM | 3 Likes Like |Link to Comment
  • ImmunoCellular: Post Hoc Analysis Of Disappointing Phase II Trial Of ICT-107 [View article]
    Yes. That is the standard of care.
    Dec 16 09:14 AM | 2 Likes Like |Link to Comment
  • ImmunoCellular: Post Hoc Analysis Of Disappointing Phase II Trial Of ICT-107 [View article]
    You raise a good point that I tried to address in my report. ICT-107 is using 6 pre-selected peptide antigens in their vaccine. We do not have any data from this trial to determine if patients expressed all, some or none of these antigens. It could be the case that ICT-107 could not mount an effective immune response in some patients because the some or all antigens were not present. IMUC mentioned on the call that some patients are going through a second resection and biopsies may give us an insight as to the relative presence of these six antigens in these patients.

    DVVax-L exposes the maturing dendritic cells to lysed tissue from the patient's own tumor. The thinking is that all of the antigens expressed in the patient's tumor could be displayed by the dendritic cells when they are re-injected into the body. An argument can be made that this is a more personalized approach than the off the shelf approach of ICT-107. This is of course only a hypothesis without firm data to back it up.

    However, there is the potential that we could learn the answer to this question when Feurstein answers my question on why he believes that ICT-107 and DCVax-L are the same product.
    Dec 16 09:08 AM | 6 Likes Like |Link to Comment
  • ImmunoCellular: Post Hoc Analysis Of Disappointing Phase II Trial Of ICT-107 [View article]
    If the patients were not operated on, given radiation and given chemotherapy, they would probably only live about five months. It is unethical to withhold this therapy so we will never know the answer to your question.
    Dec 16 08:52 AM | 1 Like Like |Link to Comment
  • ImmunoCellular: Post Hoc Analysis Of Disappointing Phase II Trial Of ICT-107 [View article]
    Thanks for your comments. They are perceptive.

    I asked IMUC management if there were any astrocytoma patients in the phase I trial for the reasons that you cited and they stated that the clinical investigators had looked carefully to determine that only glioblastomas were included. The same for DCVax-L. I have no information other than this.

    Do you really think that there could be a meaningful placebo effect in glioblastoma?

    Let me ask you a question that I don't know the answer to. Could you pre-select any 15 patients of whom 8 would have survival beyond five years based on age, resection status, health status and other prognostic factors at your institution.

    The Stupp trial data of temozolomide plus radiation initially defined median overall survival as 14.4 months for standard of care. A retrospective analysis of Stupp showed that the most fully resectedand healthier patients had about 18.2 months of survival. The delta in both the ICT-107 and DCVax-L trials assumes that the control arm will have 18.2 months of median overall survival. I am not aware of any other data that would suggest that standard of care could provide greater than 18.2 months.
    Dec 16 08:48 AM | 5 Likes Like |Link to Comment
  • ImmunoCellular: Post Hoc Analysis Of Disappointing Phase II Trial Of ICT-107 [View article]
    I have no idea as to whether the Company will gain compassionate use in Germany. If this were to, it would indicate that the German regulators after looking at all of the patient data came to the conclusion that there is a high probability that DCVax-L is providing benefit, is safe and should be made available to patients. This would pretty much destroy Feurstein's argument that DCVax-L doesn't work and there is no chance that the phase III trial will work. It would be hard for Feurstein to argue that the German regulators were pumping and promoting penny stocks.
    Dec 16 08:24 AM | 6 Likes Like |Link to Comment
  • ImmunoCellular: Post Hoc Analysis Of Disappointing Phase II Trial Of ICT-107 [View article]
    In the limited amount of data that we have on drugs based on immunotherapy-Yervoy, Provenge, ICT-107 and DCVax-L- there is a strong suggestion that a subset of patients experience a long duration of effect. If this is the case with ICT-107, there is some potential for further separation of the survival curves as survival data on the remaining 57 patients come in. This is not a prediction, just an observation.
    Dec 16 08:16 AM | 7 Likes Like |Link to Comment
  • ImmunoCellular: Post Hoc Analysis Of Disappointing Phase II Trial Of ICT-107 [View article]
    The FDA approved Avastin for recurrent glioblastoma on the basis of a 20% response rate with a four month duration of effect. MRI imaging is particularly difficult in the case of Avastin because of its anti-angiogenic effect. However, your comments on progression free survival are valid observations.

    The decision by IMUC management not to release the number of deaths in the ICT-107 arm and SOC arm in the 67 deaths is also something that I can't understand as I wrote in my article.
    This trial was dramatically under powered. I wonder what the results would have been with temozolomide in a 124 patient trial.
    Dec 16 08:08 AM | 5 Likes Like |Link to Comment
  • ImmunoCellular: Post Hoc Analysis Of Disappointing Phase II Trial Of ICT-107 [View article]
    In a previous article in which you attacked DCVax-L, you said that DCVax-L would fail but that you had an open mind on ICT-107 and implied that you thought that the phase II trial had the potential to be successful.

    Could you share your reasoning on why dendritic cell vaccines don't work? We have one example of a disappointing phase II trial with ICT 107 and a regulatory approval in the case of Provenge. The phase I results for ICT-107 and DCVax-L show some impressive duration of effect of about five years in roughly 50% of patients. The five year survival in the broad population is somewhere between 4% and 10% based on the data I have seen. Even if all of the patients in the phase I/II trials were healthy, fully resected and may have had other positve prognostic factors, it is hard to think that these are the only reasons for the duration of effect and the drugs have no effects. However, this can only be determined by doing clinical trial.

    In your previous comments you answered that the reason that dendritic cell vaccines don't work is that they are weak. Some of us couldn't follow this in-depth explanation and perhaps you could expand on this for us. While you are expounding on this, could you also explain why you believe that ICT-107 and DCVax-L are identical products and will have identical clinical trial outcomes?

    I have never guaranteed that the phase III trial of DCVax-L will be successful. As you may or may not know, both large and small companies have phase III trial failures. My judgment is that there is a scientific rationale for doing a phase III trial and a reasonable chance for success. This is a decision process that investors must go through on all drugs in development. I may be right or wrong but I have laid out my reasoning in detail. When you wrote your article in which you said that you had an open mind on ICT-107 you apparently agreed with the line of reasoning that there was a basis for doing a phase II trial. In no way did you say that there was no basis for the trial and that ICT-107 would fail. Your line of reasoning was exactly the same as mine. 

    Dec 16 07:56 AM | 28 Likes Like |Link to Comment
  • Northwest Biotherapeutics: An Analysis Of Its Transforming Balance Sheet Restructuring [View article]
    Can you give the reasons why you believe dendritic cell vaccines won't work besides your macro view that oncology trials run by small companies have a high falure rate? I will grant you that point and you have played it very well in building your brand. Let's move on. Immunotherapy is the hottest area in oncology with the checkpoint inhibitors and autologous T-cells that look to kickstart the killer T cell response to cancer. The dendritic cell cancer vaccines have the same objective and because the dendritic cell is the major antigen presenting cell; it is reasonable to think of it as way to bolster CD 8 cell response. This is a very promising approach. This doesn't mean that it will work as there is a high risk involved in working with paradigm changing therapies. However, sometimes they work. I offer monoclonal antibodies and recombinant DNA as examples. In their early days they were constantly assailed by skeptics, but they worked out OK as they are the essence of the biotechnology business today. 
    Dec 12 05:51 PM | 5 Likes Like |Link to Comment
  • Northwest Biotherapeutics: An Analysis Of Its Transforming Balance Sheet Restructuring [View article]
    Read my report on IMUC published on November 11, 2013 http://seekingalpha.co...

    This trial result is not unexpected for me and I think that dendritic cell vaccines for glioblastoma do have biological effect and am hopeful that they will be commercialized. Here is what I wrote in that report.

    The most positive trial outcome would be that ICT-107 hits its primary endpoint and shows an 8.0 month increase in median overall survival versus the 18.1 months expected for the control arm; the effect on the stock would be profound. Generally a 4.0 to 5.0 month increase in an aggressive cancer like glioblastoma would be viewed as a major clinical advance. With the mild side effect profile seen with this drug, the clinical benefit would be magnified through greatly improved quality of life. I would not be surprised to see the stock quadruple to $10.00 with such data. In the event that the data is disappointing, there would be a devastating effect on the stock as its whole dendritic cell technology would come under question. I could see the stock below $0.50 in this outcome.

    Based on the very strong results seen in phase I, I would be shocked if ICT-107 does not show some therapeutic benefit relative to control. Investors should consider that this may not be a binary event. There is the possibility that this trial could fail to reach its primary endpoint and still allow the company to define a path forward. For example, I think that a 4.0 month increase in median overall survival might be sufficiently encouraging to begin a phase III trial. It might also be possible to define sub-groups who benefit most and could be the basis for a phase III trial, though benefit for the broad population is not shown. Management has discussed such possibilities in each of the last two quarterly conference calls.

    I have learned from long experience that predicting trial outcomes is hazardous. My best judgment is that the primary endpoint won't be reached but that the data will still warrant conducting a phase III trial. This is not a judgment based on objective data. I do buy into the thesis that the patients in phase I for ICT-107 were healthier than those who were enrolled in this phase II trial so that results will be less robust. I also think that the primary endpoint calling for an 8.0 months improvement in median overall survival (something like 26 months) is a very high hurdle to jump over.

    I think that the initial reaction to an announcement that the trial failed to meet its primary endpoint would cause a swift decline in the stock. There are a substantial number of investors that I call the "Twitter traders" who write and think in terms of 140 characters and will not try to understand the entirety of the data. A major purpose of this note is to prepare readers for this possibility which I view as the most likely outcome; it could result in a major buying opportunity. Remember that my most likely case is that the trial will not reach its primary endpoint, but will show a path forward for doing a phase III trial. Of course, all of this is data dependent. This would be a strong positive for ImmunoCellular and the whole field of cancer vaccines. It would suggest that cancer vaccines are a new and viable option for treating cancer and that IMUC would be at the forefront of this.

    I have seen some reports from a few investors who in contrast to the widespread pessimism of Wall Street types believe that the phase II data will be so good that the Company can file for regulatory approval. Current management has downplayed this possibility, but prior management had been more upbeat on the possibility. I hope that the trial does reach its primary endpoint as this would be good for patients and investors. However, in this event I take the point of view that the Company could probably not file for approval and would have to do a phase III trial.

    The phase II trial was conducted at two different manufacturing sites and while the process at each was similar, it was different. The FDA in addition to requiring that clinical data be convincing for regulatory approval, requires that the manufacturing process used in clinical trials be the same as that which will be used for commercialization. This is to assure that the products are manufactured in a rigorous way that assures that the product proven effective in clinical trials is the same as that sold commercially. IMUC has not yet settled on the manufacturing process that will be used in phase III. Because of this, I believe that even in the event that the phase II trial meets its endpoint that IMUC will be required to do a new phase III trial in which the manufacturing process is validated.

    So what does one do with the stock? In my most likely scenario, I see the trial as not reaching its primary endpoint and resulting in a sell off led by the Twitter traders. I own a small position in the stock on the basis that I think there is much greater chance of the trial reaching its primary endpoint and perhaps quadrupling if my judgment is correct as opposed to complete failure that ends the development of ICT-107 and destroys much of the stock price. I want some exposure to this possibility. I think that the most likely outcome is an in between scenario that points to a path forward, but could have a short-term negative effect due to the Twitter traders. This could be the point at which I might significantly increase my position in the stock. Obviously, this is dependent on the data.
    Dec 12 05:54 AM | 5 Likes Like |Link to Comment
  • Northwest Biotherapeutics: An Analysis Of Its Transforming Balance Sheet Restructuring [View article]
    You missed my point.

    The data is encouraging on rindopepimut although median overall survival at this interim look in both cohort 1 and 2 did not yet achieve statistical significance. In cohort 2, rindopepimut did not achieve the median progression free survival endpoint.

    Stay tuned. I have an update coming on rindopepimut.
    Dec 11 06:53 AM | 3 Likes Like |Link to Comment
  • Northwest Biotherapeutics: An Analysis Of Its Transforming Balance Sheet Restructuring [View article]
    Ridiculous
    Dec 11 06:48 AM | 2 Likes Like |Link to Comment
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