@LearningEachDay. Let’s me assure you, that apart from the ethical objections (however illogical ), there is a good reason for avoiding umbilical sourced MSCs....the jury is still out on thrombus formation. Mesoblast is covered by its patents either way, but I have personally spoken to Silviu myself in the past about this ...he prefers not to risk using umbilical cells...despite the fact that they are much cheaper to harvest and to replicate. The latter is why many University clinics who want to get hold of smaller in the quantities use them as an easily available source. I must admit that in recent years I have not seen many clotting cases reported....but bone marrow derived MSCs have the largest dataset and a very good safety profile. I am sure the FDA would insist on five year clinical trials for UC MSC’s to test for safety issues ...which is a problem...we don’t need right now.
Apologies for my recent absence from this thread. I was doing in depth research on a few others stocks...I think the information drought will end with the 4C at the end of the month...if not before. I was back in the market today picking up shares. The problem facing us now...is finding a regulatory path that the FDA feels comfortable with. Mesoblast has just presented a new treatment paradigm and the boffins need to get there head around all the datasets. I think the ARDS data to be presented shortly, will push Novartis across the line in terms of confirming a form of partnership ......and the treatment for ~biologically refractory Crohns Colitis is the dark horse that i hope will come out of nowhere to surprise us all...but that will require further trials to be conducted as the Cleveland Clinic has only a limited number of people enrolled . I believe, the most likely case moving forward with a treatment for CLBP is a $30m trial involving about 300 patients for 12 months duration . If investors don’t want to stick around that long...that’s their choice. I’m back( pun intended), but I will have something to say in the near future about management shortcomings...to say that they were fortunate to secure the backing of Surgecenter is a massive understatement....Silviu may have been tremendously unlucky that the ARDS interim analysis emerged 2 days before the closing of the Novartis deal..but I believe the share price only held up because the prime brokers were not prepared to allow the shorters access to any stock lending facilities and actually forced many to close positions as the stock became unborrowable. Rumour has it that a sovereign wealth fund decided it would no longer lend stock out . Mesoblast shareholders were fortunate to avoid much dilution in the circumstances. Not cool Silviu ...get those balance sheet nasties (Hercules and NovaQuest facilities) sorted out PDQ !
How on earth did the Board sanction a phase three trial for CHF without supporting data on diuretics from the phase 2 results ? I had to look long a hard through the most extensive disclosures in the US FILINGS to even see a mention of this particular risk. Having said all that , how people can accuse the company of cherry picking datasets when they can show COMPOSITE ENDPOINTS made up of at least three MACE. I feel strongly that the FDA have a duty of care to prevent false positives in clinical trials . Although Mesoblast has been coy is revealing certain data , such a Grade 3 mortality in ischemics with non elevated CRP , the degree of efficacy and the totality of the data ...screams out to me for an accelerated approval path....not that the FDA give a toss what i think...sadly.
The main problem we may have is that precedent for most recent clinical trials is focused around small molecules therapies with their toxicity profiles which bear no resemblence to MSCs which have an exemplary safety record . Apart from a few contentious trials (watch the theatrics over at Biogen with their approval for their Alzheimer’s treatment ) the FDA do not seem inclined to want to upgrade their regulatory pathways . Hopefully, they will soon acknowledge the incredible datasets the Company has recently produced from some rigorous and well executed clinical trials. Despite legislation such as the 21st Century Cures Act meant to champion the cause of biologics they have so far hidden behind their protocols. In my view , the agency is a dinosaur not fit for purpose. I note that the UK had a vaccine programme which allowed continuous, rolling submission which meant that the UK had finished phase 3 trials when the US was finishing Phase 1 test.Mr Peter Marks is well versed in the treatment of leukaemia patients from his own career path...so how do you explain the efficacy of our clinical trial results for paediatric acute sr GVHD where it was shown that 49% of our treated patients were diagnosed with Grade D symptoms (where mortality normally is 80-90%) .
Before any of the armchair critics , croak that Mesoblast has yet to prove a mechanism of action, I suggest that you listen to a video presentation of four experts in the NEJM which followed the FDA approval of Entresto (Novartis gold standard heart therapy for CHF). The presentation included two of the main trial investigators who were specifically asked to explain the mechanism of action for Entresto. They replied (in general terms i recall ) that they were not sure, but had narrowed it down to about four different probabilities. When i looked further into how their clinical trial was conducted they had enrolled many patients who were subsequently discarded when they received a pre qualifying therapeutic in the weeks before which they adversely reacted to , whose mechanism of action was similar to Entresto. Full marks to Novartis , they legally found a way of excluding approx 20%? of their patients who might otherwise adversely prejudice their trial...all perfectly legally. Incyte , had their own ways of “enhancing” their Reach trial results (all perfectly legal) by allowing the trial investigator protocol to make use of some very surprising treatments as best available therapy against Ruxolitinib. Still, lousy efficacy in the most seriously ill patients should not detract that the FDA understood the MOA and harsh toxicity profile of their kinase inhibitor treatment . Don’t get me wrong..Ruxolitinib has much better efficacy in treating PV and Myelofibrosis which it had originally been approved for ...but i believe it will be slaughtered in a head to head against Ryoncil in sr GVHD.
So Peter Marks, its time to call time, on kicking things into the long grass and wear some long trousers. How the FDA can approve Ruxolitinib as their gold standard therapy , when it is found wanting against best available therapies in Grade 3 & 4 Gut, Liver and Multi Organ acute steroid refractory GVHD cases. Anyone with specialist knowledge in this area can see that the ST2 biomarker is a remarkably accurate biomarker for confirming the null hypothesis assumptions used and abused by your review team.. to cast doubt over the results of our single arm patient group in our phase 3 trial. Please don't ask us to murder young children by insisting on another RCT just to prove a point ...surely the results of nearly 1,000 children and adults from the long running EAP in the US and the highly successful TEMCELL in Japan count for something? I think the most likely way this delicate negotiation for Ryoncil will go ....will be the traditional face saver routine . Peter Marks will probably ask Mesoblast to make a new BLA submission to a new review team over the next 6 months ...so due process is seen to be enforced. If that happens, I would anticipate a successful outcome post the year end ..say Jan/Feb 2022 approval for Ryoncil. I sure wish they would hurry up !
Please do not rely on any of the facts,opinions or wild speculation in the above post, when making an investment decision . OP
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