banter and General Discussion, page-11384

You are waving MSBs obscurity in my face and calling it transparency -

You quoting form the september 2023 announcement -

"Mesoblast intends to generate in the coming months new
potency assay data for RYONCIL showing that the product
used during the pediatric Phase 3 trial MSB-GVHD001 was
standardised as to its identity, strength, quality, purity, and dosage form… and that commercial batches made for the pediatric indication will meet the same standard”

They don't say there what is being measured - TNFR1 levels and IL2Ralpha inhibition levels are not mentioned. But those were mentioned at ODAC. They are the matrix potency assay components - in just two parts. The amount of those molecules in picograms per mole of picograms per cell or some unit of measurement is the dosage form. Is the strength.

MSB does not say HOW it intends to generate new potency assay data (let alone say what the factors are that it is measuring (but the requirement to preserve the relevance of their clinical trial (to have at least one adequate and controlled trial - a prereq for a BLA) GVHD001 constrains them to using what they measured in the potency assay of that trial) - and HOW they generate new data matters - because if you don't have a good method your science will be rejected as bad science - as bad methodology from which conclusions aren't reliable.

This shows that they are actively working on producing new data to meet the FDA’s expectations regarding batch-to-batch consistency and potency.

But its intentional (foreward looking - they hadn't done it yet at that stage (sep 2023) and they don't specify what they are going to do specifically and why (methodologically) that will help strengthen the case. Its too vague.

Furthermore, they’ve been clear about the FDA’s position:
“FDA noted that the lack of a suitable potency assay for the RYONCIL product used during the Phase 3 trial MSB-GVHD001 for the paediatric acute GVHD indication has prevented the trial from being considered an adequate study for the purpose of demonstrating substantial evidence of effectiveness required for a marketing approval”

This provides a clear explanation of why the previous trial was not sufficient and what is being done to correct that.

That was exactly why I predicted the CRL ahead of time - that statement was no news to me (I deduced it from logic and science) - it was only news that MSB was acknowledging it.

I disagree that there is enough detail to show that what is intended (at september 2023) was enough to correct that. Missing is an explanation of a) the particular potency assay components and their mechanisms and b) what was going to be done to get the new data.

Putting new product into new patients is something that could be done. Testing retained samples is something else. The second isn't the same as the first. What is done matters. Specifics matters.

They’ve also communicated the broader steps they are taking: “To address the adult indication, Mesoblast proposed an externally controlled single-arm registration trial design in adults and children over age 12 with SR-aGVHD… to be underpinned by a suitable potency assay”

In sep 2023 - that is merely MSB making another attempted redeployment away from doing a controlled two-arm adult trial - the FDA's recommended approach (because it validates the potency assay at the same time) with a lesser alternative than a randomised two arm adult trial with a control group as part of the same trial. And to be underpinned by a suitable potency assay is merely acknowledging - the last one wasn't and the next one needs to be and the FDA should agree to the potency assay ahead of time.

But this is all september 2023 - MSB didn't say anything that didn't fit my understanding until end of March 2024. Everything they said fit my understanding of what had happened until Silviu and MSB heard something at end of March 2024 - where Silviu changed his tune - in mid March of 2024 at the hidden gems webinar he was still stressing over potency assay stuff.

These quotes directly refute the claim that Mesoblast is being vague or hiding critical information.

On the contrary - they are too vague and non specific. The don't say what the potency assay components are to be or how methodologically they are going to proceed - this is vagueness only acceptable to people who didn't understand the level of technical detail and the problems of confounding that had causes the CRL in the first place. Its superficial only.

And far more recently than september 2023 Silviu has said they didn't provide new data (as in new patients) they provided new analysis of old data - but again they didn't say what that new analysis was.