Analysis of the EAP, page-197

@dplane, My previous comment was a bit unfair since re-reading your post it's clear you were referring to coagulation parameters. Agreed, some of these patients will arrive in serious condition with a history of previous clotting problems and will already be taking oral anti-coagulants. Others will need more aggressive anti-coagulation as their clinical course plays out. All who arrive in the ICU are started on or are already getting heparin, except the few who are actively bleeding.

We know those little prongs on the virus corona are able to dock with ACE2 receptors in the upper and (unfortunately) lower airways. That receptor is involved in regulating the complex angiotensin conversions, which as the name implies help control "tension" in small blood vessels that regulate blood flow. No surprise, these patients arrive in the ER with ventilation/perfusion mismatch in the lungs. In other words, some areas of the lung are ventilating = moving air in and out, but there's no blood flow there for gas exchange. Other areas of the lung, where there's damage to the small air sacs, are perfused with blood but there's no fresh for gas exchange. There's evidence these "V/Q mismatch" problems are in part caused by clots in the pulmonary micro-circulation as the virus disrupts angiotensin and sets of inflammatory cascades. And the novel pattern of V/Q mismatch is what makes C-19 ARDS "different", especially in the "happy hypoxemics". Problem is, there are also ACE2 receptors in the small blood vessels throughout the body. So, if the virus gets into the circulation, clotting may occur elsewhere, and in unexpected patterns, as in the young adults with relatively mild respiratory symptoms, but who present with a stroke. Or the heart may become irritated leading to the increased mortality in patients TREATED with hydroxychloroquine/azithromycin. Or the olfactory bulb may be impacted leading to loss of smell. Or little lesions may appear on the toes. Just about every medical sub-specialty is now reporting some unusual manifestation of this virus, and the common denominator for many problems is infection in the lining of small blood vessels that have ACE2 receptors +/- clotting.

And I agree. With a bug this nasty, an illness this complex, and with all the different variables, better to do a careful and full study and get it right, rather than rushing results for short-term gain only to find out they don't hold down the road. I'm confident the cells are handling the problems, but I think there's a reason the FDA said treat at least 45 (+45 placebo) before you take a peek, rather than a quick 12 like in the EAP. Complex illness with manifestations that are not homogenous. Patient population that is not homogenous. Success in C-19 will be icing on the cake. Best for Mesoblast to put up solid numbers no matter how long that takes, rather than shaky, rushed results like we've seen from some of the other companies, which leave doubt. I've never felt MSB "hypes" like some of the other companies out there. Presentations are straight-forward announcements of the fact without raised voices, false excitement or hyperventilated pumping. Here's where we are, here's where we're going. Instills investor confidence.

@gerzensee, I think poor Yoda may have been modeled on Ben's portrait from his later years?

@Ratfink, thank you for posting the diagram, a picture is worth a thousand words. The more I look at it the more the audacity of it shocks me. If a competitor can't beat you to market with their inferior product ...

I'll post some thoughts on Europe tomorrow. Left-e