MSCs/iPSCs will treat Covid-19 ARDS during the inflammatory stage of the disease. There is no doubt in my mind about this.
MSC therapies have been investigated around the world in a desperate attempt to curb the damage being done by Covid-19 ARDS, and the early results are extremely promising. Various companies and their products are involved including the Abu Dhabi Stem Cell Centres’ (ADSCC) UAECell19, Athersys’ Multistem and Mesoblast’s Remestemcel-L. Athersys presented their phase I/2 study results investigating their product Multistem in non-COVID-19 ARDS in May 2019. They demonstrated a mortality rate of 25% vs 40% in the placebo group, and reduced hospital time, ventilator time, and a rapid improvement in pulmonary function. ADSCC’s trial has now treated more than 2000 patients and researched have concluded that the average duration of hospitalisation with the treatment has been reduced from 22 days to just 6. The early analysis seems to indicate that patients on the therapy were 3.1 times more likely to recover in seven days than those on standard therapy. Compassionate use of remestemcel-L in 12 patients within New York saw 9/12 patients successfully come off ventilator support within a median of 10 days and 10/12 survive during the period of March-April 2020. This is in contrast to a major hospital network in New York City where there was only a 12% survival (38/320) and 9% came off ventilators (38/445). While this does not serve as a true control, it does show a stark contrast that is unlikely to be due to chance.
This exerpt^ I wrote ages ago, around May last year, and post it here: /threads/msb-trading-2020.5158541/page-18657?post_id=45739722.
Since then, the data has only got stronger. These studies exemplify and describe the effect:
And oh, what's this? A clear mechanism of action that is demonstrated by a reduction in inflammatory cytokines CRP, TNF-a, IL-6 while increasing anti-inflammatory marker IL-10???? Was this not one of the FDA's reservations regarding Remestemcel-L?
Yes, I know cells have their differences, but for the most part, they're nuanced and if one MSC/iPSC works - it is likely another will too, just with varying degrees of potency. I back that MSBs years of iterating and developing Remestemcel-L didn't make it less effective than generic stem cells, although I know that out of body culturing does lead to a degree of loss-of-function.
Yes, I also know some of those markers are 'not significant'... BECAUSE THERE ARE 6 PATIENTS. Increase the n and if the trend is maintained it will achieve significance. Interesting again that some individuals here appear with the highest levels of inflammation see the greatest reduction, and that CRP is the best predictor of efficacy.
Not to mention, GvHD and Covid-19 ARDS have very similar etiologies. The therapy has an effect in pSR-aGvHD, regardless of the CRL, so you could expect a similar effect in ARDS.
So. What will MSB's trial see?
Probably a reduction in death, hospitalisation, inflammatory cytokines, and rehospitalisation. Will it achieve significance? Depends what subset you look at, one with an elevated CRP probably would likely reach significance. For those that are going to chastise me for talking about sub-group analysis: The trial has failed to meet its PE, the whole point of following up the data is to look for a signal of efficacy in the study population or a subgroup thereof.
But look - the risk with the Covid-19 ARDS indication isn't really about the efficacy, we will almost certainly (in the absence of god-like secondary outcomes regarding days hospitalised and re-hospitalisation) be doing another trial, which will be funded by Novartis if they choose to stick around.
That's where there is a bit of a question mark for me. The deal will obviously need renegotiating because it is 3 months later than Novartis wanted a successful, complete, RCT in the indication so that $500 million is not going to be received - at least not in full. However, they will have some data that could potentially justify development. Cynata's position is interesting, they have a significantly lower market cap and are an easier target for acquisition - but they lack US RCT data and are limited in their trial area. I think it comes down to how much of an advantage does Novartis get from the US FDA guided RCT. Ultimately - Novartis signed the deal for a reason, a clear belief and understanding the tech works and is valuable, a belief that MSB has the freedom to operate from an IP perspective, and they thought they were backing the winning horse. Their executive team and their lackeys will do far better analysis on this topic than I can, and I am also sure they have an NDA in place and have information that I don't, so I just have to trust it.
Intellectual property in the area is also a shit show, all cellular therapy companies are stepping on each other's toes but aren't doing anything about it until they get the revenue. Athersy's was pioneering the space until Covid came and MSB cut the line. Freedom to operate could be risky, but I need a patent attorney to do that DD for me.
I can't imagine it taking too long for the NIH to report the data - already longer than I thought - but I guess if they just flag it as a 'failed trial requesting follow-up' it won't be as high on the priority. All we can do is wait and understand this is a rate-limiting step that MSB is not in control of.
Just gotta wait, the secondary endpoints should turn up some gold, Novartis are there for a reason, let the dust settle on the IP battle after we generate some revenues.
Gang Gang
MSB Price at posting:
$2.16 Sentiment: Buy Disclosure: Held
(20min delay)