It’s true people are speculating. Since we are,
1. A slide UCLA publicly provided in a ground 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.
