FDA ODAC Meeting Material discussion analysis, page-332

After reviewing MSB's thesis (it is like a thesis of 127 pages, small print, full of figures and tables). I agree with most of the analysts that cover mesoblast. The questions raised by the FDA was defendable and that I am still confident a majority of the votes will be a resounding "yes" come 3am tomorrow.

There has been many comments on HC about the FDA comments. But i just wanted to point out what I think was the most important information I've seen:

1) Jakafi treatment should be revoked for patients with grade III & IV disease, due to lack of efficacy. The FDA questioned the use of CONTROL group Overall Response Rate (ORR) of 45%. Yet, Jakafi treated grade IV and III patients have an ORR of only 44.4% and 40.7% (average ~42.5%), respectively. while in patients with grade II, the ORR was 100%. This suggests that the Jakafi only works in patients with milder disease, whereas Ryoncil works best in grade III and IV patients (Page 96). Of course we are comparing two different groups of patients (12+yo for Jakafi and <18yo for Ryoncil), so the ORR might be different.

2) Safety: I don't think there was much safety concerns. These patients were very sick and Mesoblast has addressed the safety data well.

3) Efficacy: for all studies there was no issue with the description/presentation of data etc.. Efficacy was shown in both EAP 274 and GVHD001/002, despite not having a randomized control arm. I must say that the description for Crohn's Disease (page 74), and Type I diabetes (page 75) were NOT well written. It was confusing, there was no description on why the study was conducted, why anti-HLA antibody was measured etc..and doesn't add to the study. In fact, there was a typo making it almost impossible to understand Crohn's Disease data (page 74: "...At Day 28, 32 (8 placebo and 14 remestemcel-L) of the 33 patients tested had negative anti-HLA antibody test results"). However, I do understand why Mesoblast has decided to include these study, they were included in the Safety table.

4) Mechanism of action. Although the mechanism of action of MSCs is not completely defined. I give full credit to Mesoblast for showing a well support mechanism of action of MSCs through TNFR1. I think the scientific data backing such mechanism was clear. Although I would love to see Mesoblast spend more time talk about what happens when these MSCs are activated by TNF, and support the study by showing data from patients after treatment with MSCs. what happens to the level of IL10, IL6, TNF, IL1, IFN, PGE2 etc... instead of solely relying on the literature (as results from the literature would likely been done in animal models or on petri dish)

Finally, my first impression of the questions from the FDA was that it wasn't too bad. Although I have ZERO experience in defending an FDA proposal, but I would be HAPPY to rebut against such comments if they were from the reviewers of my manuscript/thesis. As per Mesoblast's released statement yesterday, these comments has been discussed with SI and team in numerous prior meetings with teh FDA, so one should chill out and let the PRO do their jobs.