MSB Trading - Aug 2020 on, page-788

I am still wading through reams of information...but i want to make the following points.

The FDA draws attention to the failure of the trials conducted by Osiris. Well isn’t that a surprise. Then they ask the Panel a perfectly reasonable question...should we ignore that clinical data ? and consider the single arm study (with all its limitations )...backed up by the subsequent EAP data and all the supporting information from Temcell...not to mention the Magic Consortium of world experts who retrospectively corroborated the trial results for GVHD001 against a control group of similarly matched patients from their database.
I think the answer for a whole multitude of reasons , is yes (please see my previous posts on subject). Don’t forget in the briefing document they also mention that Jakafi, the gold standard therapy for adults, (which IMO has a woeful AE profile), was approved as it was the only therapy for an unmet clinical need in patients over 12.

The briefing document concludes the absence of safety concerns relating to Ryoncil in SECTION 5.3 and furthermore on page 61 specifically highlights the much lower incidence of cytopenia compared to Jakafi. As far as safety...there is no real issues.

Efficacy is a harder nut to crack, with technical arguments over data responses ...but the phase 3 trial conducted by Mesoblast was correctly conducted and the results will speak for themselves.

The issues over manufacture, are logical because the FDA is trying to tie down manufacturing protocols which need further clarification as this is the first stem cell therapy to seek approval. I feel that most of the concerns regarding potency assays etc, are generic in nature, and seek to further enhance the CMC Procedures for the industry as a whole moving forward. The FDA wants to share the burden of approval with the panel of experts because I believe that they know should approve this BLA application..despite acknowledging that the precise mechanism of action has yet to be determined . If that shocks you...you obviously have not seen many other briefing documents because many medications have poorly understood MOAs . It is perfectly reasonable to question the correct number of passages and population number doublings because these factors are known to affect potency if the limits are abused.

MESOBLAST HAS IN MY OPINION SHOWN OVERWHELMING EVIDENCE FROM AUDITED PRODUCTION RUNS THAT ITS MANUFACTURING PROTOCOLS ARE ROBUST AND REPRODUCIBLE .

The FDA ,are in my opinion, covering their proverbial backsides, when they draw attention to obvious risks of populating a master cell bank with different cell donors . There are many technical challenges which Mesoblast has had to face to show batch to batch consistency.....i think they have reached an acceptable standard. I trust the panel will agree. Ultimately, Mesoblast can fall back on the statistical “p” values it has achieved to demonstrate scientifically that the manufacturing protocols are acceptable. I suspect the International Stem Cell committee will need to detail cell characterisation and potency with greater clarity moving forward , now that so many ways of harvesting and administering mesenchymal cell payloads are emerging. No therapy can ever predict to 100% accuracy, differences in how one cell donor will affect another patient receiving those cells, but after

I think that Ryoncil has shown proven efficacy in trial data for the last 10 years ...there are no real safety concerns and leaving children with no treatment programmes for an unmet need with up to 90% mortality is not going to wash with the panel. The ODAC has done its job in highlighting all the issues...i believe the Panel will scrutinise the data and weigh up all interests and then recommend approval.

I could be wrong of course. But that is my opinion .

Lastly, i am very encouraged by the new optimised therapy which shows much greater potency. I think it is logical to assume that this will lead to improved efficacy over existing clinical results data. Very impressive. I bought 20,000 at approx 3.845 today. OP


Please do not rely on the accuracy of facts or opinions expressed in this post when making an investment decision.