Avid Bioservices Inc (CDMO)

[Protector]

What in heaven is a SURVIVAL EVENT event?

Do you also have that strange feeling with PPHM's last PR!
I had it since the moment I first read it, I knew this was not bad news but couldn't pin-point why, and it kept hanging in such an extend that I decided to look closer into one paragraph that keeps coming back. Mainly the bold part and the red focus.

To further focus the strategic direction for potential upcoming trials, Peregrine just completed an analysis of overall survival (OS) data from its Phase II clinical trial comparing bavituximab plus carboplatin and paclitaxel versus carboplatin and paclitaxel alone in front-line patients with Stage IIIb and Stage IV NSCLC. This analysis, with less than 60% of survival events, indicated that while the bavituximab containing treatment arm currently demonstrates a median overall survival of over 14 months, there was not a meaningful enough difference in survival between the two arms of the trial that would support the advancement of this combination. Full results from the trial will be presented at a future scientific meeting or through publication.

Now remember English is my 3rd language so if I read this wrong then pls correct me.

1) What is a survival event? I understand to concept of eventing (eg: to die or a censor event, etc) which is a change of state (something that happened such as the patients from being alive now being death or a patients from being part of the trial now being censored, etc).

So what is the change in state between being alive and sick and part of the clinical trial after you underwent the needed transition that qualifies you to be part of the 'SURVIVAL EVENT' group? Does PPHM make a difference between people that were sick and are still alive but still sick and those that survived (as in complete response) and are alive and no longer sick, hence survived their cancer. That would qualify with the term 'event' because the patient migrates from having cancer to not having cancer anymore and hence 'survival' is more then just being alive in that context. Why do they come up with this strange wording as part of a double negative (see below) rather then a straight forward statement. Who would care much about the stats since they stop the CT anyway.

2) Less then 60%, that is 0 to 59%, survival events. So they are saying that NOT 60% of the patients (LESS THEN 60%) had this survival event. Now for vagueness this can count because that is a range of 0 to 59% survival events. Given that our science posters numerous times posted that CT's are typically stopped at 80% eventing (death patients in the traditional for everyone to understand way of saying this) we may assume PPHM would certainly have stopped the test at 80% deaths also. So we can narrow the range of the PR statement to (rephrased): 20 to 59% of the patients (=still less then 60%) survival evented (whatever that may be) and are therefor still alive.

3) Placing the abouve range (0-59%) in the context of the elapsed time since end of enrollment, the MOS of 14 for the Bavi arm and the "Stage IIIb and Stage IV NSCLC" patients this is quite an achievement. And so thinks PPHM using the wording "...,indicated that while the bavituximab...". The while here conveys the surprise! WHILE they have a MOS of 14 Months which normally would have been good if the control arm would have been in historical statistical range it is not good because that control arm performed so abnormally well that it kept close to SOC+Bavi, WHILE this is actually impossible because the SOC alone has proven numerous time not to be able to achieve these results.

So in terms of clinical trials it isn't a good MOS because PPHM says that "there was not a meaningful enough difference in survival between the two arms of the trial that would support the advancement of this combination" and that is what a CT requires as FTM explained to us before all this.

That brings us to A) the surprising control arm results of Q1/2012 that outperformed historical stats and the fact that for the arms NOT BEING SUFFICIENTLY SEPARATED this tendency of outperforming MUST HAVE LASTED till now because otherwise the control arm could NEVER have staid close to the Bavi arm.

How did the control arm do that ? It can't, we know from historical results that the SOC in questions doesn't have the ability/working substance to achieve those results and we do not only know that from an occasional instance but we know it from ALL historical results of SOC and SOC control arms for this 1st ln NSCLC indication.

In that context I would like to emphasize that PPHM did not say "less then 60% survival events" in the Bavi arm! They made it a CT wide statement, so ALSO the control arm produced its share of survivors which makes sense if both arms had to stay close to each other but which cannot be explained on SOC only.

4) Why confuse the cat. Unless it was PPHM's intend to make sure my concierge didn't understand how well my investment in PPHM was going to become I can find no reason why they needed to construct this totally out of the common double negative phrase:

This analysis, with less than 60% of survival events,...

"LESS THEN" followed by "SURVIVAL EVENTS" rather then the traditional eventing (deaths).

So, no matter what the reasons is they could have said less then 60% is still alive, sufficiently awkward as such, instead of saying that "less then 60% (=0 to 59%) survival events". It would still have been vague but we would have understood it better, however we would have asked the KEY question in less then 5 seconds, "so many survivals, why we stop now!" and the PR wouldn't have been perceived as "bad news" by the market, because 'perceived' is the correct word in this context.
In 2nd ln NSCLC SK said "more then 50% is still alive". Even that, also quite vague, statement had more clarity then the above double negative because you new that AT LEAST 50% was alive. Now you can guess between theoretical 0 and 59% which makes me thing the real range is between 50 and 59%.


Conclusion
So then, WHY this strange sentence construction? Why do you stop a clinical trial with such large number of survivors. Why and how will you present this at a scientific conference AND how is one going to explain that SOC normally has an historical MOS of x and now, in this one PPHM clinical trial, has a MOS of x+y where y is so large that PPHM writes in a PR: "the arms are to close to continue the clinical trial" (or something like that). A scientific conference is the last place where you can hide that comparison. Its full of FTM's, endoc's and other guys like that who will immediately see that the pictures isn't correct.

It is my personal opinion that there are only two explanations and one 'issue'.

The first explanation is the one offered before. If Bavi disables PS from suppressing the immune system it make no sense to combine it with a SOC that suppresses the immune system itself and then stopping this clinical trial is what PPHM had to do, cut the cost and effort and use the data for the safety database, safety that AGAIN is consistent in this trial. But I wonder if that path has been blown into our ears and now we proliferate it on this board. There is clearly no information that surfaced on my question related to SOC's that suppress immune systems, and more specifically the SOC in our 1st ln NSCLC CT. "It is said to suppress the immune system!", still wondering say's who, where?

The second explanation would be a side effect from the 'issue'. The issue at hand is of course the surprising results of the control arm. The FDA will be (have been) interested to know what exactly happened because such a deviation from historical statistics for the control arm could point to something else and is an irregularity they should investigate if they have some professional attitude. As some posted already I don't think the FDA wants a second 'dose switching' case for a same company for a same cancer type for a same drug (Bavi). That would force them into a FUNDAMENTAL investigation of a general tendency of tempering with/boycott of clinical trials under the noses of gov agencies.

Believe me that WOULD BE front-page news and would reflect on political leaders and Parliament/senate supervising these agencies. The Bavi cases, IMO, only surfaced because Bavi outperformed and survived the dose switching. So who knows how many other drugs are being tempered with. If this is a consistent practice this is undermining the health of the citizens and massive gov endorsed fraud costing more lives then any of the recent wars.

PPHM, via IR, did a TREMENDOUS effort and went to great lengths to try to stop (us among others) for qualifying the 'dose switching'. That is because they have a vested interest in it otherwise they wouldn't do it. Therefor I think that the 2nd ln NSCLC events and the 1st ln NSCLC events are related and will be handled intra muros with PPHM being largely compensated for keeping quite (which is good for us too).

Will that be a Breast Cancer BTD, or maybe even one for NSCLC in which case stopping 1st ln NSCLC makes even more sense, or an unreasonable high partnership pre-payment, or a settlement behind Insurance limits sponsored by another party, ... ?

The recently intense hiring at PPHM and the hired profiles would point towards some form of production other then for clinical trials. So a BTD could be it. I believe less in an AA for 2nd ln NSCLC as someone posted they don't give out these AA's after approving PIII design as the design itself is different when an AA is granted. I think that reasoning may be correct until proven otherwise by example and that an AA can be excluded.

I'dd like to add to that that our drop to 1.11$ was an attack because if this was a regular market reaction we wouldn't recover on such short notice, we are already almost 50% recovered from last weeks drop! Why, if this was such bad news! So we are playing in a typical scenario as the ones described by Cramer where II's and fund managers make the marked behave opposite to the real final news that matters. However, this was one of these wild events that we may expect more and more in the future and that I posted about before. Up-Down, more-up, less-down, more up, less down and so on which will make us progress to higher pps but always with these waves. Each time shares are shaked loose.