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CEO Itescu needs to go, page-60

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dolcevita

30,299 Posts.

1826

06/08/23

11:56

Post #: 69183904
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Originally posted by Phaedrus: ↑

Hi @LeftYahoo

glad to see you're posting. My opinion hasn't changed since last week. I think we're closer than ever to success, despite what I see as a lack of clarity with terminology.

The thing that the FDA has required in the CRL is not a 'trial', as I read the ASX announcement.

It's 'further data'. This is Real World Data (RWD) that the FDA want to see - the kind that can generate Real World Evidence (RWE). There's no mention of a randomised, controlled trial.

In the ASX announcement, what MSB said it would do in response to the FDA requirement of further data was not referred to as a trial, viz:

" ...Mesoblast will conduct a targeted, controlledstudy in the highest-risk adults with the greatest mortality. This adult study is "

Each of the underlined words published by Mesoblast Ltd is critical IMO. As are the words not there.

CEO Itescu referred to it as a 'study' throughout the conference call. This makes sense to me i.e. a prospective, controlled study.

Not randomised.

Not placebo-controlled.

Then David Stanton, Jefferies, started talking about duration of an 'adult trial' & CEO Itescu went with that, making the point in passing that the anticipated duration was expected to be 'substantially less' than 18-24 months in duration.

John Hester, Bell Potter, then brought the Q&A discussion back to 'an additional study', and CEO Itescu talked about an 'adult program'. Then, for some reason which I can't explain, CEO Itescu then closed with a comment about an 'adult trial'.

So, which is it in your opinion? Trial? Study?

This image extract from John Colcato's article on the FDA's RWE perspective in the NEMJ may assist MSB stakeholders to come to grips with the issues as we now must wait for the 45-day Type A discussions:

I'll provide in a separate post some notes for HC readers on the value of a nonrandomised interventional study. In that post I'll differentiate between the value - from an FDA perspective - in a retrospective observational cohort study, as announced by Prof Kurtzberg - see https://www.onclive.com/view/dr-kurtzberg-on-long-term-os-for-remestemcel-l-in-pediatric-steroid-refractory-agvhd - , and the value to be had even from a nonrandomised interventional study in a single-group trial with an external control group derived from RWD.

IMO we'll also now deal with that pesky legacy concern at the manner of selection of the null hypothesis in GVHD-001.

Sure, there's a short delay for MSB. But the FDA will get some fresh, prospective RWE, it can tick its 'pivotal' approval boxes for first-in-field therapies, it can delay having to deal with the flood of biologics a little longer, it has more time to get proper funding for its biologics licensing review/ administration & it can do all this without killing the company (maybe). So, everyone's a winner folks.

Except the children.

Who have to wait a bit longer. And that's still, essentially, on the FDA (IMO).

MSB is still looking good, from where I'm sitting. Please don't panic folks. DYOR and don't simply believe or accept the opinions you are reading here now (including mine).

Cheers, and GLTAH

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Yes stay calm when others are losing their heads.

Originally posted by LeftYahoo: ↑

@Domesticgod,

My opinion has changed since last week.

The FDA is not requiring the trial be done in adults. I believe the Company still has the choice to run a trial in adults or children. The Company has chosen adults, not because of an FDA requirement, but because some consider it unethical to run a placebo-controlled trial in children. I'll let the ethicists debate that point. The whole foundation of RCT's is that it's ethical to run a trial when a medication remains "unproven".... because that's the only way to prove it. Note especially that proof of a reduction in mortality in an RCT requires.... higher mortality in the control arm. How else can you prove there's been a reduction?

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It's not just babies!

IMO It's unethical to run a double blind trial in adults WHERE you have zero risk on safety AND there are zero alternatives and a mortality rate of over 70%. Was it 80% I can't recall now because the stats come in thick and fast and now people are turning on SI forgetting that we have on the Board an ex FDA senior administrator who has been guiding us.

This has been SI's preoccupation to SAVE LIVES. Plus the academics concern too. Plus we has a negotiated outcome on appeal, plus guidance from the underlings as they went through the process and then stymied at the final hurdle.

Hard to predict what the FDA will decide given that it has been all over the place. The decisions they make need to be seen in context of the safety and the unmet needs it defies all reason.

It's clear to me that the FDA do not like being told what to do. They are AMATEURS in relation to this technology which is a world first. You know that!

You also know that SI and team guided the FDA on stem cell policy guidelines and probably inadvertently made them look like fools.

The entire decision is shameful but instead of blaming the FDA given this entire context, people are going in for the kill on SI.

Take a step back and have a rethink please.

This is a CALL FOR CALM. Usually you can be relied on for that and some decent perspective. I'm disppointed in you but nobody's perfect.

Originally posted by Leapzig: ↑

You were all over the possibility of a BLA so your instinct is on. What do you think, is it curtains. It is a blow to see LeftYahoo's change in sentiment.

Was it you @@stocksa who wrote about BLA #2 lodged as an open approval, that perhaps it should have been lodged as an AA. A technical error in administration. We see that the response from the FDA was that a trial in adults is required. Perhaps this is in response to the open status of the BLA and not an outright rejection in SR AGHD for under 12s.

Is this not the most likely path forward. Relodge SR AGHD as an AA for under 12s. At the same time run the adult trial concurrently. Assuming they can get the funding needed to keep the lights on as well as run the trial.

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The company looks like getting funding from the partners in the academic world. They must be aghast at the compound stupidity involved here given that pharmaceutical drugs get routinely waved through. see my points above to LY. SI indicates this funding source in the Corp Comm

Originally posted by stocksa: ↑

It might even be curtains now as all credibility is lost
When an old long term shareholder like leftyahoo starts to have credible big time doubts about the whole shebang …..you have to have doubts

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stay calm and re listen to the Corp Comm. I have several times and it rewards once you set aside the emotion. IMO.

Originally posted by Leapzig: ↑

BLA #3 they will have an adult trial, 6 year survival data and better manufacturing. It is time to bring in external Legal along the journey and 'minute' every conversation with the FDA. Decisions taken by Mesoblast made on interpretation in discussions with the FDA should be peer reviewed by someone other than MSB staff. Better lobbyists with Congress also needed. Lets hope SI acknowledges that these were his mistakes which has led to rejection #2 and learn from them. There can be no mistake #3 or it will be curtains.

Pretty obvious from this point forward, follow the money. If shorts and their merry band of posters become more relentless then we know their agenda is to cripple the Company in order to force a sell off on the IP. Small redemptions going forward from SI, get funding sorted quickly, keep to timelines and leave nothing to interpretation.

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Absolutely correct. Plus MSB forced them to revise by going to appeal, and it seems some in the FDA didn't like it.
This is about professional standing and jealousies as well as vested interests and incompetence.

People are being very reductionist by slicing and dicing every aspect of the technicals and alarmist in their thinking. The legal team and the academics are setting in for a hell of a fight and we should support SI think rationally and try to reduce the bloodletting. There is funding and the rest of the programs will be put on ice from what I heard on the Corp Comm.

This is a David and Goliath fight but people are just in shock. They need to recalibrate, and stop personalising this in an attack on SI.

This is world first technology, we have met their requirements on the production and consistency end.

We have lead the FDA where they were clueless.

We need to step back and see this in greater context on the legals and the technology, you are absolutely correct on the fight ahead.

I have NOT changed my sentiment, or at least changing it back and digging in. There are accumulators out there who are seeing the bigger picture even if M&G cannot.

Originally posted by nippy: ↑

I think Krause and SI received assurances that if they met certain standards for the various issues a trial would not be required and approval received with the collegial people they interacted with.

But they got screwed by higher ups at the final decision stage.

Whether legitimately or corruptly who knows.

No trial done meant in was 'breakable' in Gordon Gecko terms regardless of what was said earlier.

When the consensus was 80% approval and 20% not approved the trial issue was behind the 20% figure.

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Correct but breakable is in the wider context, ridiculous. See above.

Originally posted by dachopper: ↑

It is very easy to throw stones in this circumstance, but to really throw a stone, you need to look at all the facts and then see where the alternative path was going to take you.

Some are saying that the company should have launched every trial under the sun 2 years ago.

We know FDA agreement for CLBP, and the following trial design has only just completed late last year, into this year. So they could have started maybe 3 months ago, and be down to 50 mill in the bank.

We also know the FDA would not let Mesoblast initiate another trial until the potency assay was agreed with them, and it's only just been agreed by FDA?

So had we started an adult trial 2 years ago with the unacceptable potency assay, all that would have happened is a cash burning exercise.

What are the alternatives, and how do you expect they would have been funded.

Expand

Totally.

Last edited by dolcevita: 06/08/23

MSB Price at posting: 47.0¢ Sentiment: Buy Disclosure: Held
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