@dolcevita, You're off to a bad start saying it would be unethical to run a blinded clinical trial in adults with aGvHD...more on that in a minute.
I'll agree to reflect calmly if you agree to reflect rationally.
Over 4 years ago after years of clinical trials and $$1B+ of paid-in investor capital SI decided to apply to the FDA for a biologics license. A momentous decision because it takes time, $$ and expertise to prepare a BLA. Despite having run trials in multiple indications with two different product candidates, he chose to apply for a license to market to young children based primarily on "studies" using historical controls and without benefit of even one successful large prospective RCT, let alone two.
That turned out to be a big, costly mistake. You can rationalize it however you want... FDA bureaucracy and corruption? Big pharma/Incyte resistance and subversion? A citizen's pithy complaint? Discrimination against a non-US company? Unethical to run a proper RCT in children? The one "no" vote on ODAC? ALL of the above or NONE of the above, I don't care. It was a mistake in sizing up the global situation by definition because it failed. And someone more adept at getting new meds approved and dealing with the FDA probably would not have chosen that indication in that history-laden vulnerable population with those shaky data.
OK, let's give the kind-hearted, doctor/professon, non-businessman the benefit of the doubt. He gets a second chance. Rather than following the advice in the CRL and going for the Type A meeting he's now scheduled, he chose to double down and dispute the CRL. Moreover, he misled investors into thinking the "well-established" dispute resolution process had a reasonable chance of success based on his reports of interactions with the FDA and hiring of additional expert personnel. Another bad judgement because again he failed. For whatever reason, makes little difference. In a small biotech burning $$MM per month, the primary job of the CEO is to make good decisions that do not fail. Medicines get approved all the time so there are CEO's out there who know how to do that. No excuses allowed this time around and you'll note SI had none to give. Not even a mea culpa. Ho-hum, let's try something with adults like we maybe should have done after the first CRL.
In a company as opaque as this one, that's not acceptable to me as an investor, though I do continue to support the concept of therapeutic allogenic MSC therapies. But we need someone who can get the ball over the goal line. SI might make a good CSO, but he's proven he doesn't have what it takes to be a CEO. ..
Now, let's take a quick look at your assessment that it would be "unethical" to run a double-blinded trial even in adults because of high mortality and "zero" alternatives... Really?? I would strongly disagree. I think your misconception of "zero" alternatives is common among investors leading to a perception that patients who fail on steroids are somehow abandoned to a corner and get no treatment. Nothing could be further from the truth. These patients get intensive care. Besides ruxolitinib which is FDA-approved for SR-aGvHD in patients 12 and above, there's a long list of other "immune suppressants" and "immune modulators" these patients may receive right up to the end... that indeed may account for the small percentage that do survive. The list includes cyclosporine, sirolimus, tacrolimus, mycophenolate, azathioprine, methoxsalen, methotrexate, pentostatin, belumosodil, ibrutinib (approved for cGvHD), infliximab, rituximab, Anti-thymocyte globulin, IV human immune globulins, ethanercept,..in addition to ongoing corticosteroids. And there are some new mAb's currently in clinical trials. The timing and combination of these various immune therapies may be considered "Standard of Care" as it's defined by leading experts in the field of transplantation medicine. Needless to say, treatment is complex and mortality remains high in cases that progress despite best SoC.
By definition, rem-L is an unproven medication. Promising but unproven because it lacks a license. Which requires "proof" according to a legal definition. If you personally had a condition with... let's say a 70% short-term mortality rate, would it be unethical for you to participate voluntarily in a RCT pitting rem-L against best SoC including the one FDA-approved medication?
I think not. In fact, that's the very foundation of the scientific evidence-based method for getting meds approved: large, randomized, prospective, blinded clinical trials where you have a chance to get the medicine under study. May you benefit from it. Maybe you do worse from it, meaning you would have done better not to get it. Statistics will ultimately decide, not anecdotes. Since no one knows for sure... it's generally not considered unethical to participate in a RCT. At least for adults where you can make your own informed decision to participate or not.
Incontrovertible positive results for a large RCT... that is what is lacking in the current BLA. One person is ultimately responsible. Enough learning on the job, get someone who had done this job successfully. SI might make a fine CSO, but he should be relieved of his CEO responsibilities henceforth. IMHO. Left-e
(20min delay)