@LeftYahoo Thank you for a comprehensive summary of the reported data. If you look through some of my past posts, I let the statisticians opine on the calculations, that is not my forte…I just need to be able to reference them. I remember looking up the formulae used with Bayesian Analysis calculations and my eyes started to glaze over. Before I come on to the reference the p values I was discussing, I looked up the Yates correction you applied…only to find its use was questionable for small data sets...noting for larger data sets it has a much smaller impact. I understand that the FDA will want to make an adjustment for type 2 error in the null hypothesis but this is when the substantial new dataset of patients in the EAP study 275 should provide assurance . I found the FDAs arguments about the null hypotheses particularly pathetic bearing in mind 89% of the patients in the trial were Grade C/D with 50% Grade D. For some reason people never adjust properly for these factors despite well documented hazard ratios for disease stratification and ethnicity (more difficult to match ) for example. Ruxolitinib in one trial had enrolled 92% white patients (see Kurtzberg comments) and only 4 kids under 18 received Rux in the study. Two of the best available therapies used in Reach 2 were already proven failures according to GVHD specialists including members of the ODAC panel….and yet Rux was only able to match mean overall survival over BAT after 11 months . Even then the results got confounded by the cross over. Lets face it for ultra orphan therapies with an unmet need there are hardly hundreds of grade D patients coming into the hospital every month …even for adults.
Of particular note is the overall survival rates achieved by Remestemcel in the non responders ..unlike therapies like ECP where they fall off a cliff.
Back on to the 28 day primary endpoint for GVHD001 , i thought for ease of convenience I would just take an abstract of Kurtzberg’s published findings.
I believe you said you had not seen a paper on the adverse events of Ruxolitinib relative to Remestemcel. I have therefore provided in table 3 of the link below the information you require….and for parents administering Rux to their kids , take a deep breath before reading.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983491/Sadly i cannot go over all your points at the moment ….but I hope this provides more meat for the debate. Always a pleasure to discuss points with you.
By the way, my initial knee jerk reaction to the 2nd CRL was bitter disappointment with Silviu. I would say to shareholders , be careful what you wish for. SO long as you have a CEO with a major stake in the Company your interests are aligned and you are less likely to suffer dilution from management who have no skin in the game. Believe me, this is not my first rodeo . It is obvious now that the FDA restricted new trials whilst the 1st CRL was being dealt with which must have made partnerships all but impossible until the issue was resolved. Now ask yourself what would have happened to your shares if Silviu had fessed up completely about this ? It is well known that most Pharma companies never come clean on the full contents of a CRL for competitive and a host of other reasons.. including panicking shareholders . Furthermore , how confident would you all have been if they started a trial for aGVHD in the middle of the Covid epidemic which I read made more than half of trials suspend recruitment in the 1st Q of 2020. Just imagine sorting out the confounding factors if any of the patients enrolled had hospital acquired infections.
The problem now with valuing this company is that we have to consider dilution from a further capital raise otherwise investors will start to have going concern issues. When the Company has adequate funding I suspect the market cap would be treble what it is now. After all , we are one pivotal trial away in several major indications with RMAT designations and we just have to repeat our incredible safety record and efficacy in a small patient population for aGVHD. If M&G has walked away and there is no Plan B (which i doubt) shareholders should be concerned . I am sure that Silviu is right now pruning every overhead to the bone and squeezing every last cent out of his remaining cash. His repertoire of skills is impressive but completely overstretched … perhaps he should be more focussed on the clinical side where some would say he has already bitten off more than he can chew …the appointment of an executive chairman, may be forced on him if there has been a breakdown of trust with his key stakeholders.
To sack him is going too far. It like replacing Lady Gaga …how the hell do you replace Gaga ? OP
Please do not rely on the facts or opinions expressed in the above post when making an investment decision.
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