OK, so lets get this straight @Barman76: this is a public forum where (im)posters exchange their personal view. It is not my duty, responsibility or my job to reply to your 7 posts in a time frame of 24h. I don't owe you anything. I reply to posts when I have the time and as I see fit. Low content one-liner posts, even when they come by the dozens, none of them providing links, or telling me to look for a previous post (and there are many) where there is a link - to then find the link being nothing more than a company issued asx announcement, which was issued at a time when there a contradictive interviews issued with numbers that I could actually cross reference against peer-reviewed papers at the time, then there is a good chance that I have better things to do than replying.
@benelong I explicitly exclude you from the above as I value your input and have therefore been very happy to explain my view and share the info I have used to based my assumptions and investment decisions on - whether they were right or not (a the time). There are many other posters on the MSB thread that I also highly value, as I am genuinely interested in their views, as they also tend to provide their sources. I believe a source provides anyone that is interested with the context and allows you to make up your own mind. I don't see it as "spoon feeding", rather a way to have a healthy discussion, even when in the end you agree to disagree.
I am more than happy to repeat my assumption from back and provide my sources as it shows that (at the time), the figures on the website didn't match the interview, but the interview however did match the general consent (at the time):
I therefore used 100mL as an average per donation and multiplied that 700 MSCs/mL = 70,000 MSCs - ignoring the fact that the cells SI is referring to are "rare (approximately 1:100,000 in bone marrow) mesenchymal lineage cells" (https://www.mesoblast.com/).
You take these 70,000 MSCs through 20 doublings as mentioned above, and you come up with 73,400,320,000 (A) MSCs per donor.
We know that there are 72,000,000 cells in a TEMCELL bag and according to their website, they use 20 bag per patient per treatment, which makes it 1,440,000,000 (B) MSCs needed per patient per treatment.
A / B = 50.97 treatments per donor.
Given that MSB's treatment is for children, you'd assume that they use less than 20 bags per patient per treatment and therefore most likely end up with more than 51 treatments per donor. Now combining that with the "two or three donors for a large clinical trial", it does sound reasonable to assume that a large 180 patient (children) SR-aGvHD trial would require that many donors.
HOWEVER:
There are also papers describing back in 2008 already, describing the expansion of MSCs using two different methods and achieving doublings of 23-25 and a maximum cell number of 7.16 x 10 11. If you then use the above mentioned 20,000 MSCs mentioned in the interview and multiply it with the number before, you end up with between 1.7 (23) and 6.7 (25) x 10 11 MSCs (= very similar to Wagner's number 7.16 x 10 11).
It is however important to mentioned that this was only achieved from the best out of eight donors (each other donor generated far less cells) plus after 25 doublings senescene kicked in. https://www.ncbi.nlm.nih.gov/pubmed/18493317
That's why - at the time - I found this interview to be very confusing as quite frankly, based on rather specific numbers mentioned in an interview (which I find to be very rare), if you actually bother using a spreadsheet and punch the numbers in (as German Accountants generally do), the numbers just didn't add up.
@Bazsa you mentioned that SI has made a comment about a recent SI interview. Here is the link (dated 21st March 2020): https://www.twst.com/interview/interview-with-the-ceo-and-managing-director-mesoblast-limited-nasdaqmeso-1 I found this statement to be particularly powerful: "[...] Using our media, they can be quickly grown up and expanded in very large numbers. They are ideal to use from a single donor to treat literally thousands of unrelated recipients. So unlike CAR-T therapies, which are patient-specific autologous, our therapies are all off-the-shelf allogeneic. That is unique to their cell type and allows us to scale and manufacture large batches of reproducible products from individual donors. Now, each of our Phase III programs has products made from different donors to ensure that there is no donor-to-donor variability, and this has already been verified. At the end of the day, the final batch of products that goes out the door is the same no matter which donor it came from, but very few donors are needed for us to make very large numbers of therapeutic doses for our commercial needs. This is a very scalable and efficient manufacturing process."
Given the above reference however, I am sceptical, which again, is my personal opinion to which I should be entitled to.
Why is the above even an issue?
We know that MSB/JCR are using more cells than Cynata's P1 trial (I'm sure that someone will be quick to point out that Cynata only enrolled 15 patients in their P1 trial - yes correct but the same people also celebrated the results of a 12 person COVID-19 clinical trial in the US - congratulations by the way. Well deserved and I say that without any sarcasm!):
Who knows what FujiFilm is going to do in their P2 trial. Maybe they look at the above and conclude, that a higher dose than the one used in Cohort B (1/4 of MSB's cells) could achieve an even better outcome. But even then, if they double the Cohort B dose, it is still half of MSB's dose. Hopefully FujiFilm will get the ball rolling soon(ish).
This matters for multiple reasons, which I suppose are more or less connected: more cells = higher cost (btw, given the context, calling it an "eye watering treatment charge" is a bit misplaced in my opinion) more cells = potential issue of "inter-individual donor variability = potential batch-to-batch consistency issues = more testing required = higher cost
If you are telling me now that this is not a "thing", then lets have a look at the PMDA's "Report of Deliberation Results" for JCR's TEMCELL (dated 2nd September 2015): https://www.pmda.go.jp/files/000215658.pdf
The PMDA was then satisfied with the measures put in place to control the risk associated with variations:
Now, lets say hypothetically there is a company that
has access to a process that apparently eliminates the need for multiple donors,
has been proven to be safe in humans (with compelling results),
has very promising pre-clinical results even when compared with MSCs from different sources in the same pre-clinical model,
is currently valued at a fraction of MSB (for multiple reasons including but not limited to very early days compared to MSB, technology still in its infancy, multiple management own goals along the way - in hindsight, COVID-19)
I made the decision and continue to make the decision for myself that it is worth a punt (and more). Thats my personal opinion based on what I could find in the public domain. It is by no means to be considered "the truth" and/or financial advice.
Given that the FujiFilm transaction has now been executed, I believe this issue has now been resolved.
If I don't reply to your post:
I might be busy trying to make a living,
be out-and-about trying to melt away the additional isolation kilos while actively practising social distancing,
washing my hands for the 20th time of the day while considering injecting disinfectant.
Have a safe week everyone and good luck to all MSB holders tomorrow. Given the euphoria around any COVID-19 announcements, a meaningful one such as yours should see another surge, and in the end will hopefully provide an answer to our manufacturing question: is there a scalability issue or not. Until then, decide for yourself and invest accordingly.
CYP Price at posting:
66.0¢ Sentiment: Buy Disclosure: Held
(20min delay)
