Ryoncil: ODAC/FDA Meeting Discussion, page-476

Bauer and Temple's presentations I think muddy the water. The overview of their presentations basically were: "MSCs are very complex, but there are tests, but we don't expect these test to be practical or done by applicants, but they haven't been done so this raises questions x, y and z".

During the questioning after initial presentations, one key question stood out on the lack of link between TNFR1 and mechanism of action to which SI responded with the following:
"“When one looks and trusts correlations between biomarkers, is essentially a sufficient patients, large number of patients to make those correlations. We have a large database. We are fortunate we have treated hundreds of patients with stem cell across multiple trials over 10 years. We can only demonstrate or identify correlations when you have enough patients. By the fact that it changes the manufactured optimization as it could, we are able to look across those timelines and learn. When you do that you see is a product used in some of the failed trials 10 years ago, which Use a product had a 50% lower level. We have that degree of variability you can see correlations in patients. The optimized product which is now the 50% higher level was used entirely in the pivotal trial phase 3 and a good portion of patients in 275. When you have such high level, high consistency as we saw in 001, and I showed you between love variability was very low when you have that degree of consistency and reproducibility in a level that is 50% higher than previously used products, it is very difficult to show within only 60 patients a relationship between minor differences and survival, those are very important clinical outcomes. Requires hundreds if not thousands of patients. The fact we've been able to do this within a limited pool that is precisely because we have improved the potency by 50% and those very abilities allow us to make those both and 60 patients only or 54 only in the trawl with the product has been significantly improved in the variability is very small, it is not possible to show survival nevertheless we are very significant outcomes in terms of biomarkers and immunomodulation that appears to be very important and related to the outcomes in these patients."