Updated Broker Report: Bel Potter, page-94

A few have mentioned MSB shouldn't have presented the previous two failed RCT's in this BLA.

Firstly, I don't think they would have any credibility if they didn't, given this data needs to be addressed in some form or another as to why the results didn't meet the primary endpoints.

Secondly, if anyone studied the Kaplan-Meier curves presented to ODAC demonstrating the efficacy of the 'improved process' MSC's on grade C/D patients (young and old), it is completely consistent with the Protocol 001 single arm trial results.

Yes, FDA doesn't consider sub-set analysis to meet an endpoint as a valid method in the first instance but it is often used to inform further trials. This is exactly what happened with the single arm confirmatory trial protocol. MSB then showed the significant differences between the two manufacturing processes in terms of CQA's and how those CQA's were the highest correlation to outcomes in grades C/D across all 3 trials, in effect validating subsets of the previous failed RCT trials using the new manufacturing methods. This definitely had a huge bearing on convincing the 9 out of 10 ODAC voters with the other brainless twit stating something along the lines of 'oh, so you expect us to believe you just tweaked a couple of things in manufacturing and all it works now'. Well, that is exactly what the data showed (both manufacturing data/CQA's and Kaplan-mierer curves) and if he was data driven, as per the mandate for even sitting on a FDA sanctioned board, he would not have made such a prejudice comment. He needed to justify that comment based on a facts instead of insinuating MSB had tried to fool ODAC and the FDA.

My main point is that MSB did turn those failed trials into some form of very useful RCT data and there is no way they could have fooled 9 out of those 9 open minded experts because they came into that meeting completely tainted by the FDA's mis-representation of the data. There is no way they would have voted for efficacy if those previous trials demonstrated truly failed RCTs with no redeeming subset data. So in terms of precedents, any success is this Accelerated Approval application will not give a green light to pure single arm study submissions, as this is not the case for Ryoncil.