1. A slide UCLA publicly provided in a grand round presentation by LL, appeared to infer all placebos had likely had recurrence events by December 2016 (most of us didn’t see the video until 2017) 2. This was based off shipping records for aliquots of DCVax-l. The shipping monitoring was discussed in the 2018 JTM paper which covered data from March 2017. 3. They rounded some numbers in that paper, which made it impossible for outsiders to determine if more recurrence events occurred. 4. A couple years later, Dr. Liau confirmed to the best of her knowledge, no further had occurred in number of crossovers. The number she gave was consistent with her presentation in December 2016. She told Lykiri he’d have to ask the company if he wanted additional information. 5. My due diligence toward the end of 2016 concluded it was likely, had this been only a standard of care trial, that 98% to 100% of patients would have normally had a recurrence by around November 2016. 6. In April of 2019, I believe, Dr. Liau stated most very long lived patients in the trial had not had recurrence events. 7. She also stated, based on her therapy outside of the trial, that many patients responding to DCVax-l had at least some mesenchymal features. Normally, under SOC, mesenchymal are more aggressive tumors with worse prognosis. 8. In 2011, Dr. Prins and Dr. Liau noticed that mesenchymal and classical tumor signatures appeared to respond to DCVax-l, while proneural was less decipherable in that regard. After that, Dr. Liau was reluctant to treat proneural with DCVax-l. 9. By November 19, 2021, WHO memorialized the new definition of GBM, which now excludes proneural tumors. 10. Back in April 2019, Dr. Liau also stated at the UW grand round (on the video we later saw) that it is important to get DCVax-l early. 11. Back in June 2015, the NIH funded Shashi Murthy with a four year grant to develop an automated closed system production method for Dendritic Cells. 12. Dr. Liau recently acknowledged (2022) cell immunotherapies have been challenging in the past to manufacture. A year prior, she stated we’ve got to find a way to get this treatment to patients. 13. One month after Flaskworks patented the dendritic cell generator, NWBO acquired them. 14. One month after that, NWBO achieved data lock in the Phase iii trial. 15. In approximately 2021, Dr. Pazdur stated any new/prospective/incoming standard of care must be able to reasonably ramp production. 16. In December 2014, Linda Powers stated the only way to meet potential massive demand, which they had been thinking about “a lot,” was to develop an automated closed system production method. 17. In or around late July 2015 (just a month or so after Shashi Murthy began his four year grant) the trial’s screening process was halted. 18. By March of 2018, it was clear to realists that over 28% of blended patients were alive at three years from time zero. 19. In 2022, Dr. Pazdur was adamant that the FDA would, in many cases, take action to protect placebos in trials that demonstrated obvious efficacy, even if that meant having to change the trial’s endpoint to an external control arm. 20. In 2021, the Lancet stated hybrid trials that could not simply stick with or go to solely placebo controlled comparisons, could be made more statistically powerful by modifying the control design to also incorporate external controls. 21. This month, Mike Scott confirmed Sawston is ready to manufacture more DCVax-l 22. This month, Flaskworks patented a more state of the art cell manufacturing system that recently added a antigen/lysate pulsed cassette feature to the patent design.
Question, how in the hell do you “buy” over a half decade of time to develop Dendritic Cell commercial manufacturing method before you take a trial to data lock?
My guess is our consternation is another person’s solution. Hopefully, in the very near future, patients will get a commercially viable product to help them with one of most otherwise feared and intractable cancers known to humans — January 2022
Imo, the SAP was completed by the end of 2019. This should have (one rare thing Ex and I agree on) included (and I think probably did) assembled ECA data.
They later stated they spent most of 2020 collecting idh-1 mutation status (slides and whatnot) on trial patients.
The acquired Flaskworks in Late August 2020. Flaskworks had finally received an important patent grant a month before. (They received more after the acquisition)
Data lock occurred October 5, 2020…. By then, SNO and the Europeans had already accepted changes in GBM definition, which now excludes idh-1 mutant tumors. The WHO would set the new/same global definition by November 2021.
International patents for Flaskwork’s, Direct’s and L’s technology increased during 2021 and 2022. Three patent applications, Direct, L and Combo, are currently under U.S. review by their respective examiners again. This time they are all being examined for decision at the same overlapping time. The latest examinations (forwarded to examiner) have been going on for [2.5] to [3.0] months. That means all should get a decision any day. There are reasons to believe they are likely to be granted this time around.
Low cost manufacturing ability was sought as an absolute necessity by Linda Powers and Dr. Ashkan as far back as 2014. Now, in 2022, the closed system automation developed by Flaskworks should be approvable for commercial manufacturing very soon, although no application has apparently been filed with MHRA yet…. Dr. Murthy and team have been working on this exact technology since June 2015, when the NIH gave them their first grant.
Someone pointed out that Dr. Ashkan believed as early as 2014 excellent commercial manufacturing would be needed for a technology that is expected to be with us for many years.
It’s uncanny how the recent additional DCVax patent applications are now lined up (one had to dust some cobwebs off) whilst the TLD/Publication appears to also be waiting, while the EDEN manufacturing process is still apparently laboring to get their certification application in. I would bet that once the application is in, the assumption will be already green lit and certification will be a formality within a month or two thereafter.
