A few things to consider:
Bigger hurdles when you are the very first, especially when using a
world first in humans.
I doubt that the departments allowing the trial to proceed would have wanted a patient to die on their watch due to an oversight in the study protocol/lack of following the correct protocol.
In July 2015, Masayo Takahashi's pioneering macular degeneration iPS trial was put on hold due to genomic issues in the 2nd patient, with one of the mutations feared to carry a remote risk of cancer. It took them 1 year (and a switch to allogeneic iPS cells) in order to announce that the trial will continue, then almost another year before the next patient got treated. And January 2018, they reported another adverse event. Even though Takahashi assured the public that it wasn't as serious as it sounded, all of the above didn't exactly help the cause to abolish safety concerns when it comes to iPS cells.
Takahashi's trial protocol was reviewed in 14 meetings with different authorities over a period of 12 months.
https://www.futuremedicine.com/doi/full/10.2217/rme-2017-0130
I mentioned it before, reason we got FujiFilm that early was due to them buying our sister company CDI. FujiFilm was quick to realise the potential of iPS cells in the field of regenerate medicine. CDI was and is selling iPS derived MSCs (NOT using the Cymerus process, hence cannot manufacture them at commercial scale etc.). they gained knowledge through our pre-existing tie-up with CDI (after all both companies originated from the University of Wisconsin, Madison, IP held and licensed by WARF).
I dare to say that without that knowledge, there wouldn't have been a FujiFilm licence option agreement that early, and we'd still be chasing Regience K.K. and all the other windmills out there.
It is not a coincidence that even today, 12 year after Shinya Yamanaka's discovery there have only been 4 clinical trials world-wide using iPS cells (with one more starting shortly from memory).
Out of these 4 trials
- only one is/was conducted outside Japan
- only one is/was conducted by a company (rather than a university).
If it was such an easy sell, why is it that only Japanese universities so far have accepted the challenge (apart from us)?
Why would we waste more money (for which we'd have to bend over even further and accept further dilution) to prove safety of our Cymerus process in other indications? That's what a Phase 1 trial is designed for - to prove safety:
https://www.australianclinicaltrials.gov.au/what-clinical-trial/phases-clinical-trials
What are the odds that any country would have let us try a world-first in a condition that is not as devastating as SR aGvHD? There's a reason our trial settled for a condition with a mortality rate as high as 80%. Not a coincidence.
We got spoiled given that our Phase 1 trial had such outstanding results, that it really turned into a Phase 1/2.
Our trial delivered results (ok, yes, less patients, still, doesn't matter for what I'm going to say) that even beat a product that has recently been granted priority review by the FDA (after already being granted breakthrough therapy status):
https://www.onclive.com/web-exclusives/fda-grants-priority-review-to-ruxolitinib-for-gvhd
Yes, that is a drug requiring to be combined with corticosteroids in order to achieve an OR of 55% at day 28 (meeting the primary endpoint of the trial).
There is a very exciting opportunity here for CYP-001 to potentially PREVENT GvHD before it occurs (as AO mentioned a while back), or to at least reduce severity, IN ADDITION to TREATING the disease after it occurs. And yes, the market for prevention is substantially larger.
If the final report doesn't get the fence sitters (large pharma) to make a move, then I don't know what will. Good thing is, there is now finally light at the end of the tunnel! Most of us have been walking in the dark for the past 3 years +, lost some on the way, gained a few new comrades, too. It has taken us much longer to get her than initially anticipated, but this is it guys, soon we'll get the answer - if we agree with past choices made by management or not.
Don't get me wrong, I'm also very unhappy with the same "partnering discussions ongoing" for the past 3 years, self-inflicted deadlines that couldn't be met etc. I didn't agree with the loan fiasco and I also don't understand the KPIs that are used in order to determine the bonus payments. The dilution back in late 2015 was also a misstep if you ask me.
However, if you ask the Japanese, they will tell you that Cynata "is the closest to commercialisation" of all iPS programs out there:
https://www.rikelab.jp/work/2121
If you believe in regenerative medicine, iPS technology, MSCs and Cymerus in particular, that Cynata is currently your best bet in my opinion, especially given our current MC and considering the massive potential.
(20min delay)