Advantages of pooling of human bone marrow-derived mesenchymal stromal cells from different donors versus single-donor MSCs
Conclusion
From this study, we propose a solution to the issue the current cell therapy field is facing. The outcome of cell therapy is often mixed and difficult to predict, and it is contributed to the heterogeneity of the cellular medicinal products. To make a consistent MSC-based cell therapy product, we pooled MSCs from three different donors at the P1 stage and banked them at P3 as working cell banks. These WCBs were the starting materials to have a reliable and reproducible final pooled product at P5. Our pooled cells showed all the basic characteristics of typical MSCs and expressed superior immunosuppression characteristics along with stable secretion of angiogenic factors. They also did not exhibit any senescence in culture and were non-tumorigenic. These pooled cells were also proven to be safe and effective and could increase the number of product sizes for different preclinical and clinical settings.
This evidence published in one of the premier journals in June 2024, does not exactly follow the party line for those advocating pluripotent cell lines derived from one donor. This is not what Cynata shareholders want to hear. By the way , the latest FDA guidance on selecting the number of donors requires applicants to discuss the requirements with the
casereviewer which is exactly the protocol believe Mesoblast followed. The FDA recognise the problem of small working cell banks for orphan designations . Of course in the EAP there was eleven donors whose cells were used so effectively.
I believe Mesoblast has now provided data to the FDA to explain exactly how some data from the
Osiris trial was confounded by downstream manufacturing issues at the USA plant…hence the apparent reported change of position by the FDA to consider Mesoblast GVHD001 results in isolation that was mentioned in the Bell Potter internal note that someone posted on Hot Copper.
From reading recent literature it is obvious, in my
opinion , that durability of response and long term mortality data, have shown that the mechanism of action for sr aGVHD is considerably more complex and multi factorial than Messrs Klinker and Bauer comprehended. Since the last CRL there has been validated biomarkers established by the MAGIC consortium in
paediatric cohorts which have been further enhanced by combining the results with Minnesota High Risk Scores to provide outstanding levels of patient stratification. Put simply the new science is making a mockery of the null hypothesis arguments of the FDA review team. The biomarkers which recognise proteins ST2 and Regenerating islet-derived 3-alpha ,are extremely accurate because they are able to discern damage to the GI tract. Ultimately the huge percentage of Ruxolitinib refractory patients, happen also to be those suffering from the latter indication. The Chairman of the MAGIC Consortium , Prof John Levine,, who is regarded by some as the worlds leading authority on acute GVHD,has been quoted in Clinical Trials Arena in a
November2023 article as follows :
Mesoblast, was a first in class MSC therapy for acute steroid refractory GVHD. As such the FDA was always going to drag its feet owing to many alternative arguments over what was the precise mechanism of action. The latest guidance documents from the FDA shows there has been considerable movement in their position in recent years. That is not to say there were not weaknesses in the Phase 3 clinical trial GVHD001 , but it was an adequately controlled trial that met its primary endpoint. The expert advisory committee of the FDA ultimately concurred with Prof Levine opinion. The last disclosed issue over potency testing has been dealt with by the back and forth of the last eighteen months with not just the regulator but also with the BTN CTN steering committee. What i find sick , is the idea that a therapy which has an accepted safety profile , proven efficacy, passed its PLI in manufacturing and advisory committee and been told that its potency assay is acceptable and they should now resubmit, should be targeted by a bunch of shorters and armchair academics when the Federal regulator has clearly opined that it is now ready for resubmission. I find these people beyond the pale. In short they disgust me. I believe the only way they can be right at this juncture, is if Itescu, Krause, Levine , Kurtzberg et al,are all delusional , when clearly they are not! The modus operandi is simple. Starve the Company of capital, or at the very least even, when they are being proven completely wrong about the science, make the dilutive effects of capital raising destroy investor confidence . With FDA authorisation of Ryoncil , the worlds investment community will be looking at Mesoblast from a position of total credibility . From that moment on we will be discussing margins , roll outs, manufacturing upgrades, label extensions and off label revenues…which should potentially be enormous. In my opinion , within weeks of authorisation , the shrill voices of the shorters will be wiped out by a stampede of investors piling into this stock as they appreciate the vey real prospect of a validated treatment for end stage heart failure and chronic lower back pain is also on the horizon . OP
Please do not rely on the facts or opinions expressed in the above post when making an investment decision.
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