Ryoncil: ODAC/FDA Meeting Discussion, page-477

The second question in regard to TNFR1 I'll turn Dr Silviu to answer the question.

SI>> 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 more than 100 patients with stem cell across multiple trials over 10 years.We can only demonstrate or identify correlations when you have enough patience.

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.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 nowthe 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 | 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 arelationship 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 Mr.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 verysignificant outcomes in terms of biomarkers and immunomodulation that appears to be very important and related to the outcomes in these patients.