Hi Hittman
That is true! And to expand on your comment, (for the benefit of other readers):
In a dose escalation/dose finding trial like this the dosage will continue to be escalated until either:
1. There is a dose limiting toxicity (which has not happened with Vaxinia)
or
2. A step up in dosage produces no significant additional efficacy - at which point the dosage is reduced to the previous step, which is then declared as the "Optimal Biologic Dose."
So the posters who have tried to portray the increasing dosage in the MAST trial as a sign of failure are either ignorant - or they are being deliberately mischievous and trying to scare people.
We already have some very good signals of clinical benefit - the CR result in Cholangiocarcinoma, the PR's and the stable disease patients - but clinical benefit tends to take a while to show up so they are assessing "efficacy" (to determine the effect of dose escalation) through a range of biologic markers. eg. T cell diversity and changes in the tumour microenvironment. The AACR poster presentation details these:
https://static1.squarespace.com/static/5b63d41b3e2d09b1f56bf483/t/6615a985cf90a236e02c61a3/1712695687606/CT182-MAST-AACR2024-final2.pdfThey are clearly happy with what they are seeing at the Cohort 5 dose level of 3 x 10
8 (300 million PFU) - because LC confirmed that they are using that dosage level for the Cholangiocarcinoma expansion group - but she did say that they are also likely to test 10
9 (1 billion PFU) in the wider MAST trial.
My comment should not be interpreted as a statement that Vaxinia is a "success." I think the initial signals are very encouraging but we will need to see more data. I'm simply saying that claiming dose escalation as a sign of "failure" is moronic.
For anyone interested in the concept of Optimal Biologic Dose, this article from the BMC Cancer journal is extremely good:
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-021-07782-zI'm not loving the depressed state of the IMU share price, but I don't see the share price as a reflection of the prospects that IMU will succeed with Vaxinia - or indeed with any of their products.
I'm relieved that IMU has massively reduced their cash burn by selling of the Mfg facility, while retaining an assured capacity to manufacture their own product. I feel that the MAST trial is progressing extremely well, with encouraging results from the low dose cohorts, but I recognise that clinical benefit to patients - change in tumour size - is a biological process and it simply takes time to happen. Later this year we will start to see data from the higher dose cohorts, and then we can all discuss whether Vaxinia is a success or a failure.
Until then, I intend to maintain an open mind and a cheerful disposition.
I also remind myself that life is for living - and we all should enjoy it as best we can, while we can, and help those around us to do the same.
Best wishes to all for a fabulous weekend!
Cheers
Dave
(20min delay)
