@ImaScientist@ZenoxCongratulations to both of the above posters...

@ImaScientist

@Zenox
Congratulations to both of the above posters for drawing attention to the Chart 1 CHF trial which failed to meet its primary endpoint but showed efficacy in two defined clinical subsets. I first evaluated this trial two years ago when post hoc analysis suggested some activity in the 200-370ml patient subset.
The reasons why Mesoblast shareholders should sit up and take notice of the results is fourfold.
Firstly ,Chart 1 enrolled ischaemic patient cohorts with reduced left ventricle ejection fraction and injected into heart tissue around the margin of the most damaged/ischemic tissue, in a almost identical clinical procedure to Mesoblast. The NT PRO BNP (one of the most accurate biomarkers for determination of likely mortality) of each patient exceeded 1000 so these patients had a similar profile to the DREAM HF-1 enrolment . Secondly, no safety issues were identified at the time with this mode of delivery even after four years post delivery....but the initial positive treatment effect was somewhat delayed and started to show effect versus control 100 days post injection. The key that no one appears to have commented on, is that the improvement over the control ONLY related to those patients receiving 19 or less injections...as shown by the chart below where survival probability was 90% after 2 years compared to low 60’s in the control and approx 55% in the patients achieving more injections. From this we can speculate that, LESS IS MORE ...certainly in relation to optimal levels of the number of injections administered and the total dose received.
I would not be surprised if Mesoblast were eternally grateful for this data ...since i believe their trial prohibits more than 19 injections (and has exclusion criteria which preclude patients with very thin heart walls which might be more likely to be damaged by percutaneous injection).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3066826/

Silviu pulled off a potential masterstroke when the CHART 1 trial announced its failure to meet its primary endpoint. In 2018, Mesoblast swooped in and secured an exclusive license from Celyad to use its C-Cathez system for a payment of Euros 2.4m. I believe it to be one of the only competing Cardiac navigational mapping system to NOGA, from J&J, which was launched back in 2005...and may have now been eclipsed by Celyad specially adapted design.
https://www.biospace.com/article/releases/biosense-webster-inc-and-cordis-corporation-release-fda-clears-innovative-cardiac-navigation-technology-/
“C-Cathez ® is C3BS’ steerable percutaneous catheter. With its nitinol-based curved needle and side holes, this new generation of percutaneous injection catheter for myocardial delivery has been designed and developed to elevate the standard of care to clinicians and patients by focusing on three key features: local drug concentration, safety, and ease of use.
With C-Cathez ® , Cardio3 BioSciences/Celyad provided the clinician with a catheter which can be safely steered to reach target sites within the heart left ventricle. C-Cathez ® permits stable contact with the beating myocardium without generating additional tissue trauma and diffuses the therapeutic agent over a bigger target area to obtain both a higher concentration and a wider tissue exposure”

https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.13031

So the key conclusion , i draw from the Chart 1CHF trial is that if we reference the results, I have tabulated above, (which are only now available from the post hoc analysis), in those 35 patients receiving 19 injections or less in ischemic patients, OVERWHELMING EFFICACY was demonstrated to the required p value. In contrast using the wrong dosage, especially when resulting from too many injections (31 patients) ..... and you can perform WORSE than the control (96 patients).

For obvious reasons, such as the Mesoblast LVAD trial data, the Phase 2 results and the comments of the DMC at the end of the Phase 3 Revascor trial , Mesoblast does not appear to have made the same mistakes as Celyad ...I also believe that our immuno selected MPCs are of superior potency to those used by Celyad in their trial....which leaves me to conclude we have a very decent chance of overwhelming efficacy when our results our published in the very near future. Fingers crossed.



Please do not rely on the accuracy of the facts or opinions expressed in the above post when making investment decisions. The author is not medically qualified and owns a substantial shareholding which may be actively traded on occasion. OP