CEO Itescu needs to go, page-390

@dolcevita,

I guess if you can't mount a rational argument on the issue, which is the performance of the CEO, the only thing left is to go after anyone who criticizes him. You're the one who needs to calm yourself a bit. Is SI some kind of an emperor immune from all negative commentary? How many times does the airplane have to slide off the end of the runway before action is taken to avoid something worse?

As for whether you're hurting or not, I couldn't care less. You feel obliged to advertise "sweet life" in your handle, which tells us a lot about your personality right there. I have no aversion to HC and post opinion and commentary periodically when I have something to say that might be of interest. I'd visit more regularly if were out to get "followers". IMO/IMHO is my disclaimer. Anyone who takes anonymous opinion on a stock message board as financial advice gets what they pay for.

You said, "Nobody has a track record of getting FDA approvals over the finish line for stem cell therapy". Wrong. You might want to do a little research. They're allogenic too. Plus there's a growing list of other cell-based therapies that now have FDA approval. "Sweet life" and your number of posts suggest "free time". Maybe make yourself useful to the board and post the list. It's a lot longer than you might think. Whether cell-based or not I'd rather have a seasoned veteran with FDA successes flying the plane than a novice who's now shown twice he can't navigate. NO one is irreplaceable.

Yes, if SI had succeeded on this approval I would be singing his praises. But he didn't succeed and my opinion of him has changed. I'm sharing it on this board so that as investors we can avoid repeating mistakes. Since I still own a significant stake in the company I'm working against my own short-term financial interests. This is for the longer term and non-financial reasons.

Let's look at what happened. We have an illness, SR-aGvHD, that occurs in patients who receive bone marrow transplants. Most of the patients have had a leukemia, which can happen to any of us or a loved one at any age. It's in everyone's interest to see this done right. Treatment of the illness is complex and evolving... starting with chemotherapies to ablate the tumor and immuno-suppressants/modulators to allow the transplant. Morbidity and mortality are high in those who develop this transplant complication and progress. By the company's own estimates some 80% of cases occur in adults. Your second task is to post a list of all the medications FDA-approved for patients under age 18, but not approved for adults. Now tell us how many of those meds are to treat illnesses that occur primarily in adults. I'm not aware of any, it's your chance to correct me if I'm wrong.

Yet the company is vigorously pursuing an approval for children when the bulk of the patient population is adult. It's a bit unusual... might raise an FDA eyebrow or two. So why is that? Mesoblast purchased the technology now known as rem-L from Osiris which had run a phase 3 RCT in adults and children with SR-aGvHD. The trial failed but in the subset of 27 children there was a positive signal... Six children died in the blinded control arm at 100 days, but only three in the Prochymal arm. (I'm using actual mortality counts not to be insensitive, but for better understanding). Promising... So Mesoblast went to the FDA and got permission to run an open-label study in 54 children, most with advanced forms of the illness. 14 children who received stem cells died. But it was calculated from an external database that 23 would have died had they not received the cells. Mesoblast also began to offer stem cells to children through an EAP. Of 51 with severe disease who received rem-L 25 died by day 100. Using the CIBMTR external database it was calculated that 35 would have died had they not received cells. Again promising... but let's be honest... far from a cure for everyone.

Those were the core data for the first BLA back in 2020. I would encourage everyone now to read the FDA publication "22 case studies where phase 2 and phase 3 trials had divergent results". In it the FDA shows multiple examples where "promising" results in small studies were found to be inaccurate when larger phase 3 RCTs were done. Sometimes very inaccurate. Here Mesoblast tried to cobble 3 small studies together, only one of which had prospective, randomized, blinded controls, and that one drawn from a larger study that failed overall. After reading the "22 case study" paper, it becomes clear that the odds of getting these 3 small cherry-picked and poorly controlled studies past the FDA were negligible. Probably should not have been attempted. And certainly after the first CRL, the company should have run the requested phase 3 RCT. Instead SI doubled down and disputed. The question becomes, Why? Fear that the product wouldn't succeed in a large trial?? Something worse?

We have posters saying the FDA is corrupt. Others saying they moved the goalposts. Others saying they don't understand GvHD. But great data cures all of those. As done by multiple other small companies. The data submitted by Mesoblast are not anywhere close to the usual FDA standard of two large phase 3 trials with randomized and blinded controls. If we had good data from a large phase 3 trial we could fight the FDA and the "concerned citizen's" letter. But objective review says we don't. The "well-established" dispute resolution process had little chance of success and should not have been pursued imho, especially... after... the FDA clearly said go run a phase 3 RCT. That message didn't register with SI during the Type A meeting he had after the first CRL. But let's trust him to sort this out after the second CRL?? With his proposal just to collect more "targeted data". GLTA investors here. We'll need it. imo, Left-e