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I totally agree HappyLibrarian, that's the scenario I prefer. I also think is a very possible one and in this case initial agreement would take care of share price before any possible buyout.
Thanks Thermo. Great points as usual.
Thank you very much OncoJock. Great to know.
With all due respect, I disagree with you and suggest you to read the followng links to understand that it doesn't work that way. So we cannot assure short interest is increasing by 5x in the past 3 days or something like that.
https://www.tradersmagazine.com/departments/equities/understanding-short-sale-activity/
https://www.finra.org/investors/insights/short-interest#:~:text=The%20short%20interest%20data%20is,sales%20on%20individual%20trade%20dates.
Bio, I now saw your post and I don't disagree with you. The point I was trying to make is the reason why I think we found out the generic name, in relation what I think is the preparation for approval, marketing and journal publication. No that they cannot use an interim generic name as you pointed out.
Bio, excellent post as usual. I totally agree and would like to add the following:
As you may remember, I have been saying that part of the 35 patients not included in any of the nGBM / rGBM arms could have been pseudoprogressors from SOC that received DCVax-L (after initially being mistakenly thought to be real progressors), but were not included in the rGBM arm because they were not really recurrent patients. If they exist, they would be part of the following subgroup of the 35:
Patients in the original placebo arm that had PFS events but were not included in the rGBM arm:
81 PFS events - 64 patients in rGM arm = 17
Now I think that some of the group of 35 could also correspond to patients that without having recurred, started receiving DCVax after it was realized that there was no placebo anymore in the trial and patients were going to be compared to external arms. Which I think was the plan from long time ago, before presenting the SAP. I also think regulators were on board from that time, otherwise why the trial ended with exactly 232 patients in the DCVax nGBM arm, exactly according to the plan, leaving the placebo short by 17 patients. If they exist, they would be part of the following subgroup of the 35:
Patients in the original placebo arm that didn't have PFS event:
99 - 81 = 18
If this is the case, the group of 35 could have a good mOS as numbers suggest. And the reason is not that DCVax doesn't work like some here like to sugest, but the opposite, that it works very well.
As previously expressed, I think final resuls are going to be better supported by this and other facts than what we have seen until now.
* English is not my native language.
Lykiri, about this:
Lykiri. Any comments about my answer?
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=170331757
I would like to know your thoughts and also I find interesting what you mentioned:
:)) Lol. Great post as usual.
Thanks a lot Doc Logic!! The same goes to you. Thanks for your great contributions.
I disagree that at most 2, but it's ok, no problem. We don't have to agree. For me, nearly 90% can be 89.4%, 90.6%, 91.2%, etc.
Thanks flipper44.
Thanks flipper, I agree with you. And I think that real progression on the other hand is more frequent in nonmethylated MGMT. Do you agree with that? Please let me know your thoughts.
Lykiri, I have 2 reasons to think the majority of the 35 non-crossover placebo patients are MGMT methylated.
The first one is as follows:
From the JTM publication we know the following:
From the NYAS we know the following for the nGBM arm:
And the following for the rGBM arm:
With this, we know that the percentage of patients with unknown MGMT methylation decreased between JTM and NYAS from 11.48% to 4.74% for the case of the nGBM arm and to 4.69% for the case of rGBM arm. Actually very similar percentages of 4.7% for nGBM and rGBM arms.
So I think it is accurate to assume that 4.715% (average between 4.74% and 4.69%) of the patients in the group of 35 remaining patients have unknown MGMT methylation. This equals to 2 patients (35 * 4.715% = 1.65).
With this, we can estimate a total of 16 unknown MGMT methylation in the whole trial (11 from nGBM arm, 3 from rGBM arm and 2 from the other group of 35 patients).
As a consequence of this, we have 22 patients (38 - 16) that had unknown MGMT methylation in the JTM journal publication and were then identified as MGMT Methylated or MGMT unmethylated.
In order to distribute these 22 patients between MGMT Methylated and MGMT unmethylated, what I did was to use the proportion of 131 MGMT methylated patients and 162 MGMT unmethylated patients from the JTM jourmal publication. With this, I obtained a distribution of 10 methylated and 12 unmethylated.
After adding the 10 methylated and the 12 unmethylated patients to the JTM numbers I obtained the following:
With this we obtain the following numbers for the 35 reamining patients by substracting the numbers in the tables corresponding to NYAS nGBM and rGBM arms from the numbers in the table above :
The second reason is that for me it makes sense that the patients that evented are more likely to be MGMT unmethylated than MGMT methylated, so I expect more methylated remaining in the group of 35.
Lykiri, I'm not sure if I understand your question (don't know if by placebo you mean the initial 99 placebo patients or the 35 remaining patients that were not included in any of the arms). But I hope this answers it. Please let me know:
Of the 38 initially unknown MGMT patients in the 2018 JA, I think 22 were identified after and only 16 remained unknown. And the breakdown of the 16 that remained unknown I think is as follows:
+ 11 in the nGBM arm (NYAS data)
+ 3 in the rGBM arm (NYAS data)
+ 2 in the group of 35 remaining patients (estimated assuming the same proportion of unknown as in the nGBM and rGBM arms)
Of the 22 initially unknown but then identified, my best guess of how they were distributed in the beginning would be 16 in the nGBM arm, 4 in the rGBM arm and 2 in the group of 35 remaining patients. But this last part I didn't use in any of my calculations, since they were then identified and just calculated it now using the proportion of patients included in each group.
Thanks a lot GPha. Really appreciate your comments.
Quote from the post I'm replying to:
We don't know, but we can estimate and theorize. Time will tell which theories were close to reality and which ones where not.
Also, Dr. Bosch said:
Doc logic, I totally agree with you and have been posting about that. I think there is a possibility that some in the 35 group correspond to patients that were initially thought to be recurrent, so received DCVax L and benefited from it. And then it was realized that they were SOC pseudoprogressors, so they were not included in the rGBM arm.
As you say:
Thanks a lot Hoffmann. The same goes to you for all the great things you share here.
Lykiri is correct. That information came from NYAS data:
The same to you biosectinvestor. Thank you very much for all the great work you share here.
Lykiri, I totally agree with you.
Meirluc continually states as facts things that are not facts and that I'm almost sure are not true.
One of his statements I don't agree with (and doesn't make any sense to me) is that the rGBM arm patients had a higher mOS than the nGBM arm patients. Actually, the numbers suggest exactly the opposite, as follows from a very simple math exercise, based on information from the final results presentation:
- From slide 39, mOS for rGBM patients is 13.2 months from recurrence
- From slide 3,"Time to tumor recurrence: ~7-8 months from surgery"
If we add 7.5 months (average time from surgery to recurrence from above) to 13.2 monhts (mOS from recurence) we get 20.7 months mOS for rGBM patients from surgery.
From slide 29, mOS from surgery for nGBM patients is 22.4 months, which is clearly higher than mOS from surgery for rGBM patients of 20.7 months.
He also keeps stating that the 64 rGBM patients in the trial are or may not be comparable with the ECAs, which is not true, as clearly mentioned in the same presentation, slides 15, 16, 17 and 21.
Regarding your question to him, I don't think the mOS of the 35 patients (that are not part of neither of the nGBM and rGBM arms) is as he states because, as I have mentioned in other posts, I think those 35 patients have a higher percentage of IDH mutated than the other groups and that actually is correlated to not having progressed. Also, after some math I shared in previous posts I think in those 35 patients there is a higher percentage of MGMT methylated than in the nGBM and rGBM arms (also related to lower progression) and finally I also think there is a possibility that some of those 35 patients received DCVax that actually helped them but, were not real progressors (could have been pseudoprogressors form SOC) or didn't classify to the rGBM arm for any other reason.
** Sorry for any inconvenience, but English is not my native language
Bio, I agree with your argument about the very small percentage of the remaining control arm as part of the total trial and think that it may even be smaller than 10%.
The reason why I think that is possible is because there are 18 patients that were part of the original placebo group but were not counted in the events of the PFS chart (these patients should correspond to censors specifically for PFS analysis, but not for OS analysis I think):
99 (original placebo group) - 81 (PFS events) =18
And also, there are 17 patients that had their progression event counted but were not included in the 64 patients corresponding to the recurrent GBM arm:
81 (PFS events) - 64 (rGBM arm patients) = 17
.
I think it is possible that part of those two groups of patients received DCVax, but were not real progressors (they could have been pseudoprogressors from SOC) or didn't classify to be part of the rGBM arm. If that is the case, they could have done well in terms of OS because of DCVax but don't be part of any of the nGBM or rGBM arms. That's why I think final trial results are going to be even better than what we have seen until now.
VikingInvest, I think all the 885K preferred shares outstanding are C shares. So they have issued around 600,000 more shares convertible to 15,000,000 common stock from July 20th until now. Look at the following statements on last 10Q together with the number of outstanding preferred reported in the S-3:
Not only those 18 (99 - 81) patients you mention. There are also 17 patients (81 - 64) that had their progression event counted but were not included in the recurrent GBM arm.
Could you explain why do you think this is related to Flaskworks?
TopelRoad, SOC can also generate pseudoprogression:
flipper44, I actually don't agree with Sluicebox numbers because the 20.2 - 21.2 months that he calculated for the rGBM arm correspond to time from surgery and the 19.3 months for nGBM arm correspond to time from randomization. In order to compare those two numbers, he needs to add 3.1 months (average time between surgery and randomization) to the nGBM arm mOS, So the comparison is 20.2 - 21.2 Vs. 22.4. This means that the patients from the nGBM arm lived longer than the patients from the rGBM arm as would be expected in my opinion.
But I agree with the observation I have seen in some of your posts that DCVax-L might work quite well at crossover because most of them were not on chemo anymore.
And what if those crossover patients are SOC pseudoprogressors initially thought to be SOC progressors. Wouldn't it be even better?
Do you think is possible my theory that part of the 17 difference between the 81 events in the PFS chart (they are not cPFS events, just PFS events) in slide 11 of the trial results presentation and the 64 patients that finally were considered in rGBM arm (81 - 64 =17) correspond to those patients and that is why interim JTM results showed higher mOS than nGBM arm? I would like to know what you and others think about this. I'm not saying I am sure about that. As you said, we will not know for sure until we have more information. Is just that some numbers I calculated support that theory. Not sure if you saw the posts were I shared them.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=169301316
I will also present your previous post in quotes, and then respond.
What I think is that those 35 patients were in the initial control arm of the trial (part of the 99) and at some point, after randomization, they were thought to be progressors from SOC, but then it was realized they were late pseudoprogressors from SOC.
If this is the case, because of being initially thought to be progressors, they received DCVax after pseudoprogression. As a consequence of that, these patients were not classified in any of the two trial arms. They were not progressors when they received DCVax, so don't correspond to the rGBM arm and they didn't receive DCVax at the beginning of the trial, so they also were not included in the nGBM arm, but benefited from DCVax.
The main reason why I think that is the case is because in slide 11 of the final presentation there are 81 PFS events (this is PFS, not cPFS or confirmed progression-free survival events) coming from the 99 placebo arm patients, but in the rGBM trial there are only 64 patients. There is a difference of 17. How would you explain that difference if it is not the reason I mention? I'm open to read any possible reason for the difference, but I think that is. I would like to know what you and others think about this difference.
I also think those patients could be the reason for having 13 left censored patients (lost to follow) in the JTM interim publication for the first 19 months from surgery and then zero in the treatment arm for nGBM from the final presentation, as I explained in previous posts.
And finally, I find possible that some SOC pseudoprogressors where not excluded from the trial because they pseudoprogressed after randomization.
Sluicebox mentioned in his/her reply to you that Doctor Ashkan said that less than 10% of the patients didn't crossover. That would reinforce this theory, because we know that at least 89% received DCVax-L ( (232+64)/331 = 89%). So maximum 11% didn't receive it. If the number that didn't receive it is less than 10%, that would mean that part of the 35 patients received DCvax at some point and could correspond to the group of pseudopregressors that received DCVax at pseudoprogression.
Sluicebox, the 20.2 - 21.2 months that you calculated for the rGBM arm correspond to time from surgery and the 19.3 months for nGBM arm correspond to time from randomization. In order to compare those two numbers, you need to add 3.1 months (average time between surgery and randomization) to the nGBM arm mOS, So the comparison is 20.2 - 21.2 Vs. 22.4. This means that the patients from the nGBM arm lived longer than the patients from the rGBM arm as would be expected in my opinion.
A lot of differences between what I wrote and what according to you I wrote. I'm sure you do that on purpose.
- I didn't assert there were 40+ alive, I said it could be the case.
- According to my numbers, patients who never received DCVax-L didn't have the highest % known 5 year survivors. If you read my post you will see that I think part of those 35 patients received DCvax after pseudoprogression and those are the ones that did better in that group.
So no bad news, good news. Results look better and better as the process of numbers being digested advances.
IkeEsq, what I have read is that pseudoprogression is also generated by chemoterapy and / or radiotherapy (not sure which one or if both). I'm not a Medical Doctor, but maybe someone else can complement on that. For now I can offer you this: