That is correct, I am definmitely not on the same or even near that level of cell biology you are, nor would I have questioned the science behind it if it wasn't for your posts on the MSB thread. I followed your arguments and tried to rephrase it the way I understood it (your explanations pre CRL #2), which they made sense to me.
Now, coming back to the earlier conversation we had about me "hoping" for MSB approval instead of a CRL #3.
I am still looking into it all, but so far, this is where I am (which could just be another rabbit hole like so many times before).
I am still trying to look for a patent in place during the P3 GVHD-001 trial that they may have reverted to now. Given that the technology is from Osiris, I was looking for patents assigned to MSB but likely with Osiris personnel, defining potency that also showed changes as well as other factors that could be revered to.
My best guess was Danilkovitch, which I have referenced a few times.
Different versions over the years, the 2012 version still active, 2017 abandoned and 2020 pending.
2020:
The 13 pg TNFRI threshold is the same, however, the invention claimed in 1. says: when all other claim versions (abandoned and the ones still active in the US until 2027) mentions: All other claims still showed readings for 27.7 pg, but that value was not included in the claim.
The pending patent you have tagged me in, "A composition comprising mesenchymal precursor or stem cells and their use," with the investors being Silviu Itescu and Paul Simmons, you can see the following: https://patents.google.com/patent/US20230398154A1/en
It continues:
It concluded:
They had these data points in all trials as each patent provided readings on the TNF-R1 expression. They now linked it to the IL2-Ra inhibition and retrospectively re-analysed the data they had from previous trials to show the improvement in survival.
That's my take so far.
After reading up more on Marks, I consider it to be a bit of confirmation bias since he is not "new", he joined the FDA in 2016 and has been the Director of CBER since 2016. His January 2024 interview in BioSpace, if taken apart, could be read as: "Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, argued that non-randomized, single-arm trials could be the best option when testing certain gene therapies for rare diseases" "“There are many rare diseases affecting dozens to a few hundred individuals in the United States where the concept of trying to do a randomized trial is very challenging at best and impossible at worst,” Marks told BioSpace. When it comes to trialing gene therapies, it’s not possible to efficiently enroll sufficient numbers of patients, either because there aren’t enough patients or because those patients won’t agree to be randomized, he explained. “It’s a situation where you can’t get the job done.”"
He however also said that: "Marks concurred, saying that one of two conditions needs to be met for CBER to consider approval of a gene therapy based on a single-arm trial. “The treatment has to create a large enough effect that it is apparent to a non-statistician that something has happened significantly to those individuals, such that having a control group is not necessary,” he explained, or measurement tools must show that “a parameter has changed enough so that we feel comfortable that it is reasonably likely to predict that something good down the line is going to happen.”" https://www.biospace.com/article/fda-s-marks-advocates-for-flexibility-in-rare-disease-gene-therapy-trials/
What does the non-statistician in you say? Survival of 67% vs 20-30% by 100 days, and what appears to be an improved potency assay as outlined above in the pending patents that has data to show from various previous trials (original manufacturing and improved manufacturing methods)?
CYP Price at posting:
28.0¢ Sentiment: Hold Disclosure: Held
(20min delay)