Replies to post #243171 on Avid Bioservices Inc (CDMO)

[Krakonos]

exwannabe I do not understand why.

Second (and more importantly), your math fails to account for the simple fact that as the trial progresses there will (hopefully) be more patients at risk in the bavi arm, thus more deaths there than in the placebo arm.

Why would more patients be at risk compared with placebo group?

Logic tells me that trial can't progress forever, because placebo group will have all patients 6 ft under at some point PRIOR to bavi's arm.

What is it that I am missing?
Am I that dense?

[foolnhismoney]

exwannabe, as you are so quick to correct others' posts with your superior tone, let me point out the following:

The phrase, used correctly, is reductio ad absurdum

not

reducto to absurdium

As a statistics genius and former philosophy professor, you should know better. Oh, really, you aren't a statistics guru or philosophy prof? One would never know.

[sunstar]

EX, I meant median, not mean. Thanks for the correction.

I did realize that the events would be dynamic and occurring over time. I didn’t want to unnecessarily complicate the description of the progression of events. I think it would be as follows:

Early in the trial there would be a preponderance of Doce events, more than 2:1. Because Bavi generally provides patients with longer survivals. As the trial progresses I would expect a growing number of Bavi events, but there would still be more Doce events than Bavi events. This, again, is because Bavi allows patients longer survival than Doce does. In, say, 24 and 36 months the ratio would be much closer, but not even. Bavi may also produce some complete responses. Some patients might enjoy some old age and grandchildren.

...as the trial progresses there will (hopefully) be more patients at risk in the bavi arm, thus more deaths there than in the placebo arm.”

Quite the statement!

The point of discussion on Opdivo, anti-PD-1, was that it has scarce targets compared to the anti-PS, Bavituximab. I’m sure you understand that, it’s just not coming across, for some reason, in your posts.

“Opdivo was 17 months O/S in the entire population.”

That’s an interesting spin. How about: in the highly restricted “entire” population?

IMO

sunstar

[Protector]

exwannebe, I am surprised that you do not accept sunstar's PPHM 2nd ln NSCLC results. We have all seen them. Ctrl Arm=5.6 months, Bavi Arm=11.7 months.

I hope you are not going to 'bend' the conversation after Dr. Brekken publicly, and with nodding authorisation of management - King, etc were present - at NYAS confirmed that the results of the 2nd ln NSCLC were BETTER then the conservative set filed with the FDA in order to get approved. I think that the case has been made more then sufficient times that the SUPER results announced on Sept 7th, 2012 have been obtained with a sabotage that was even in the DISADVANTAGE of Bavituximab and in the ADVANTAGE of the control arm.

I have more to say about this:

BTW: Opdivo targets T-cells, not cancer cells.

Yes, and that will place it in the disadvantage of anti-PD-L1 drugs who bind the PD-L1 marker expressed on the cell instead.

The T-Cells have a WIDER function. If you bind their PD-1 receptor to keep it from binding with the PD-L1 on the cell, then you are changing the T-cell's behaviour for the COMPLETE collection of cell's (cancer and other cells). And that has it's consequences for non-responders, which are the about 70% majority.

You must actually see it like this. The T-Cells have functions and then someone binds a few mushroom with their stem to the T-cell surface (BMY's molecule isn't exactly a mushroom but it is just as an illustration of the concept). Now that T-Cell is in general disabled from approaching other cells because the mushroom(s) on it's surface doesn't make that possible anymore. This means the T-cells become less effective for ALL receptor/marker expression activity in that area and that includes all interaction with:
- tumour cells (ok, that was intended, so good)
- healthy cells (bad and not intended)
- helper cells (CD-4, CD-8, etc not intended, kept from binding CD-4 glycoprotein on T-cell surface).

This last category makes the T-cell BLIND for substances in the blood stream (e.g. non-body own substance, damage residue part of some signalling, etc) that it cannot detect directly but which it detects via the helper cells such as CD-4 that express markers that bind with the T-cell's related CD4 glycoprotein.

More IMPORTANTLY for Bavituximab, the activation function FC-Gamma receptors on MDSC's, M2 Marcophages and immature dendritic cells (Bavi's immune stimulation process added to its immune suppression blocking process) as well as its workings on the adaptive and innate immune response system may be severely hindered by this. PD-L1 approaches don't have this problem because they target the immobile cell's, not those of the immune system floating in the bloodstream.

And we see what the above means in terms of side effects. Opdivo attacks a tumour at the cost of creating problems all over the place by disabling critical immune system functions.

Add Opdivo+Yervoy together and you reduce the number of responders (20% or below vs 30% for Opdivo alone). Let's not talk about the side effects because IHub's disk space would be insufficient to store them if listed. You need to take a holiday to read them all from BMY's own list.

Without Bavituximab (provided the pre-clinical results (200/300% improvement) and Dr. Brekken's enthusiasm are correct) the anti-PD-xyz alone have no future if combinations such as Docetaxel+Bavi and later anti-PD-xyz+Bavi come on the market.

Docetaxel+Bavi+Durvalumab could be an absolute MOS mover and has Earthquake potential in the Pharma/Biotech industry. Mark my words.
Docetaxel+Bavituximab will occupy the field in the mean time.

[asmarterwookie]

[color=red]...as the trial progresses there will (hopefully) be more patients at risk in the bavi arm, thus more deaths there than in the placebo arm.[/color]

Ex...was this a mix up in your wording?

wook