Found another one. The replies to it are interesting too. Link to source below.
MESO's thesis in ARDS As an $ATHX investor and avid stem cell enthusiast, I like to keep tabs on potential competitors in the space. Per this announcement [http://investorsmedia.mesoblast.com/static-files/f7c1b407-e130-4190-9283-620e0fe621a5](http://investorsmedia.mesoblast.com/static-files/f7c1b407-e130-4190-9283-620e0fe621a5) , $MESO is presenting next week at ISCT with a presentation entitled ‘Mesenchymal Stem Cell Therapy Improves Pulmonary Function and Exercise Tolerance in Patients with Chronic Obstructive Pulmonary Disease (COPD) and High Baseline Inflammation’. So, I decided to go back and look at their trial data from a phase 1/2 they completed in COPD back in 2014. The data are documented in this publication [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694112/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694112/).
After thoroughly reading through the pub, the first thing that sticks out to me is the statement, “No significant effects of MSC infusions were observed on pulmonary function or QOL indicators”. I find this ironic since the title of their presentation next week asserts that MSCs improve pulmonary function and exercise tolerance in patients. Now I am no rocket scientist, but doesn’t one statement directly refute the other (literally)? Additionally, there were no statistical differences in total lung capacity, oxygen saturation, and just about every other key outcome they measured (I’ll let you read for yourself). I wonder what data mining trick they will pull out of their ass this time.
The biomarker analyses in their COPD trial were also suspect. Levels of circulating TNF-α, IFN-γ, IL-2, IL-4, IL-5, and IL-10 were at or below limits of assay detection in most study patients, precluding meaningful analyses. Levels of circulating TGF-β and CRP did not differ significantly between baseline to years 1 or 2 in either treatment group. However, post hoc analysis of patients with elevated, circulating CRP (C-reactive protein) levels at baseline (> 4.0 mg/L in 29 of 62 patients \[14 in the MSC group, 15 in the placebo group\]) demonstrated a statistically significant decrease in circulating CRP at 1 month after the first infusion in patients receiving MSCs. IL-6, a key inflammatory cytokine with relevance to ARDS, and specifically COVID ARDS, was not measured.
If you go back to the press release for next week, the basis of their argument is that some patients with severe ARDS have significantly elevated levels of the inflammatory biomarker CRP at onset. This is the key to their thesis in ARDS since the other relevant markers could not be assessed in their COPD trial. They will undoubtedly use some of their GvHD biomarker data as well to validate their thesis. A publication entitled “SARS-CoV-2: a storm is raging” gives a nice breakdown of the so-called cytokine storm in severe COVID ARDS patients. It found that in severe cases, there is an overproduction of cytokines IL-6, IL-10, IL-2R, and TNF-α, lymphopenia in CD4+ and CD8+ T cells, and decreased IFN-γ expression in CD4+ T cells.
I’m looking forward to next week to see if they can effectively address some of these issues. I know Athersys already addressed them last week in the webinar. From what I can see in the prior COPD data, MESO still has much to prove in their current ARDS trial (even though the anecdotal data from the compassionate cases were compelling). I’m not entirely sold on mortality as a primary endpoint either. Live or die? I like a more indication specific primary endpoint such a ventilator-free days, with mortality as a secondary. Just my opinion on the endpoints, not sure if it matters to the FDA. You can make of it what you will. Anyhow, looking forward to next week.Take care and invest wisely.Cav
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