Ann: FDA Notifies Clinical Data Sufficient for Refiling aGVHD BLA, page-199

I can explain it and have previously.

Okay, well I'm not afraid of detail, or the truth, so if you want to bring out your old posts rather than rehash points you've already made then please be my guest. But I'll address what you say here, now.

There were multiple reagents used in one of 2 potency assays used in the trial.One of these reagents had inadequate QA and as a result was too variable in quality giving poor results. SI stated to me after the AGM that he thought the original assay was superior to the one that was accepted for the Adult trial. Analyzing the original trial data using potency assays with proper QA gives acceptable new data for consideration of the successful phase III trial.

An antibody used for flourescent cell sorting or ELISA, would usually be provided by a third party and could be described as being a reagent. So what you are saying fits with a previous explanation I had mooted about antibodies used to detect the levels of TNFR1 at release time could (almost certainly would give different measurements) if different antibody production technologies were used to measure the same molecule (TNFR1) at different time points.

Monoclonal antibodies are clones many modern antibodies used will be monoclonal antibodies (so they should bind a molecule in the same place - its like a lock and key but its very specific the key has to go exactly in the lock and not anywhere else) but in earlier (in the history of science methods antibodies were generated differently, more naturally, they weren't clones. So they had some variability in them potentially.

There have been science papers written in reputable journals like Cell and Nature from memory where the results of important seeming studies were not able to be reproduced from other labs that looked like they should be competent to reproduce a good finding and it turned out that difference in the antibodies made the results hard to reproduce.

SI stated to me after the AGM that he thought the original assay was superior to the one that was accepted for the Adult trial.

Lets, look at that. MSB's cells that were used in the MSB-GVHD001 trial were harvested to p2 (passage 2 - ie they grew across the dish, got trypsinzed, then were replated and allowed to grow across the dish a second time - so passage 2) back around 2009 from memory and cryopreserved so they would have used techniques and antibodies available in that sort of time period. Chances are they were not monoclonal antibodies but hybrid or some other sore of antibodies but they should have been sort of QA'd for the time to be sort of consistent - I'm not suggesting reagent suppliers back then weren't trying to provide good product - they would have been - but the techniques weren't available earlier to the same extent or sometimes they were but the knew technologies were more expensive.

Bottom line is though passage 2 for cells stored in 2009 or thereabouts and measured for the TNFR1 levels with some antibody to measure TNFR1 levels is all happening at some point in the now distant past. Whatever antibody was used then gave them the measurements they got then - and they can't change historical fact now.

What they could do, if they had retained samples of cells or cell extracts etc is test those historically cryopreserved substances with new antibodies so they could get readings for TNFR1 levels or theoretically pretty much anything that preserves across time when cryopreserved with a later antibody.

But antibody readings from old and new (different antibodies) would be like different velcro's, they'd be grabbing the molecules of interest, differently, so it would be hard to match the level of TNFR1 at passage 2 with say levels of TNFR1 at passage 5.


accepted for the Adult trial

Are you sure that's what SI said to you - because - and I might have missed an update - but I don't believe the FDA has accepted a potency assay for an adult trial even as of today? So it seems you are likely putting words into SI's mouth that I doubt would be exactly what he said to me. Although I assume you or he would be doing that innocently enough figuring the detail didn't matter because of whom you were talking to.

one of 2 potency assays used in the trial

There were only 2 potency assay parameters used in the trial - a measurement of TNFR1 levels and a measurement of IL2 R alpha levels - prohibition of against co-cultured T cells.

And those 2 as the matrix approach go way back into MSB and Osiris history, yeah in theory they could have chosen other things to do a potency assay around, and yeah in theory SI is right (was at ODAC) he could have measured other things downstream of the TNFR1 interaction with its receptor and also used those as supplementary potency assay parameters, heck in my view he could have done things like measure INF gamma levels too, but he can't do those things without a time machine from now if he didn't think to do them before.

And if he did do them before he would have presented better data to the FDA.

To grant the story MSB holder/enthusiasts want to be true SI or MSB needs (to convince sceptics like me if he cares and I don't care much if he does or he doesn't) to put some detail onto the bones of the story that doesn't contradict established facts of history - what MSB have said and done in the past - as well as the FDA and other scientists and those details also need to be things that they could have done at some point in time.