"Good vibes Here Dudes"....., page-26

Happy to discuss while the conversation remains civilized.


1. The benefit of the ‘at scale’ manufacturing of Cynata seems to have been diluted by what has been stated this week. It may still have credence but won’t be tested with GVHD as the ‘at scale’ volumes aren’t needed.

I agree, the "at scale" discussion shouldn't be an issue for a small indication such as GvHD or even DFU (less than 1 million cells per patch). The recent MSB AFR article mentioned the following (educated guesstimate?):
"Assuming a treatment at between $US400,000 to $US500,000, the group could generate sales of up to $US200 million. At gross margins of about 60 per cent, [...]."
a f r . com
https://www.copyright link/companies/healthcare-and-fitness/mesoblast-the-biotech-that-hasn-t-yet-20230802-p5dt8a
So even by taking into account that a 2D "patch" is used to manufacture the final product for GvHD, I can't see it not being commercially viable given the prices charged for FCDI's own iCell MSCs.
Using the manufacturing method as described in nature for the P1 "Proof-of-concept" trial to calculate the cost of a potentially "patched" final product is not representative as the manufacturing approach improves over time and depends on the quantity needed. For starters, they used 6-well plates - and that is where my calculation approach ends.
https://www.nature.com/articles/s41591-020-1050-x
I can't see that profit margin being consumed compared to MSB's 2D approach by an improved (compared to the nature article, pre FCDI) 2D approach by Cynata.
What hasn't been diluted at all is the argument that you must be able to show evidence that your final product works and that you are capable of replicating that outcome. As @JB1975 has pointed out, there is a clear and obvious variance in INF Gamma levels on the slides used by MSB:
https://hotcopper.com.au/threads/ann-mesoblast-completes-resubmission-of-bla-to-fda-for-sr-agvhd.7206622/page-385?post_id=66225053https://hotcopper.com.au/threads/ann-trading-halt.7340296/page-236?post_id=67440107

The inter-donor heterogenity of a product that is forced to rely on multiple donors (in MSB's case 1 donor is enough to supply treatment for 400 children) has been the downfall of the latest BLA. The data presented via post-hoc analysis was not sufficient to show that the final product will be the same potent product used in that sub-group of patients that showed an improved benefit, especially since the sub-group used to show the benefit was already a sub-group of the initial study. To be completely honest, I actually thought after going through MSB's presentations that they appear to have found an alternative IL2RA approach - and maybe they have- but they didn't have enough data points available from this sub-sub-group to provide the "sufficient, scientifically sound data" the FDA requires to approve a product for sale - and rightly so! You can't charge someone for a product when you can't be sure that the product contains MSCs from that one specific donor that provided the starting material that was used to generate the clinical data that lead to approval - unless you can show that the final product is the same, no matter which donor supplied the cells used.


2. KK’s recent comments about ‘having a P2 so good you don’t really need a P3’ are telling. I think Cynata correctly forecast the latest knock back by the FDA (along with JB and others - congratulations to all - you saved yourselves money). KK was right and the ‘P3 may not be needed’ comments seem to show that he knows it’s a foot race. I.e. P2 with Cynata vs P3 with Mesoblast.

Looking at our decline in SP, there is no need for any congratulations as we are in the same boat, for different reasons, but the same boat nonetheless.
KK could be right, yes, based on the body of evidence around MSCs as long as the company managed to correctly identify that sub-group of patients that is likely to respond to MSC treatment (see inclusion/exclusion criteria) based on their understanding of the MoA. Importantly, the clinical trial mist confirm their understanding vs. running a trial and using the generated data to form a hypothesis. That's the wrong way around.
That a small P2 study could be enough can be seen on the example of Belumosudil:
"The approval is based partially on findings from a phase 2 clinical trial of 65 people with chronic GVHD, who were in remission from cancer after treatment with a bone marrow or stem cell transplant. Three-quarters of those patients responded to belumosudil, meaning their GVHD symptoms improved."
https://www.cancer.gov/news-events/cancer-currents-blog/2021/fda-belumosudil-rezurock-chronic-gvhd


3. What would I know, right??!! But, I can’t see enough cash in the kitty for CYP to complete the P2 FDA trial. They must be sweating on a partnership IMO. One would think that MSB getting mashed again would improve the partnership chances. But, given 1. And 2. Above, will it be enough to get the deal done??!!

I believe they were banking on a DFU partnership before starting the GvHD trial. However, recruitment has been taking a lot longer than anticipated and with nothing but initial results on hand they were then forced them to do a CR at the worst time, which resulted for this stock to end up in the dog house.
Cash is tight, I agree. And too many times we've been told that the current cash runway will carry us through to X, Y and Z, just to find ourselves having to ask for more money along the way. KK's statement is however clear and on record, saying there is enough money in the bank to get us there. The product has been manufactured and paid for, the initial $1.7 million has been paid to the CRO to commence the trial already (and the remaining balance being largely ascertained at this stage), they should have had a good understanding of the financials before making this statement. If not, then perhaps it is a case of continuing the legacy of the previous CEO in which case the SP is valued exactly how it should be, based on cash in the bank (or close to it).