Sorry for delay. Second part was nice, but mainly stuff we have heard before.
Synergy Bolsters Immune Theory
VB111 and anti-PDL1 show synergistic effect in mouse model of lung cancer and melanoma. Interesting.
(1) I was thinking VB111 had single-agent pancancer activity, but it looks like there still are going to be some indications where it just is not that great. Lungs are pretty immune-tolerant, and if eliciting an immune response is key to VB111 outcomes, then it is not surprising that the mouse response data was not as stellar as most we see from VBLT.
(2) In melanoma, VB111 monotherapy is better than antiPDL1 solo. I now see why VBLT mentioned a CI+VB111 trial a few times in the past. The sooner they show VB111 to be safe through a Ph1/2 trial, the sooner big pharma will come begging them to use it in a combination. Especially a company like AZ that needs to find some way to speed their drug through several indications. Also, BMS might be interested after their big failures with nivolumab.
(3) I hope they explore the CI space beyond the PD(L)1 axis.
Combination Partner
@gr8db8, I think you are correct about AZ and durvalumab (their anti PDL1). Also, remember they brought on Rachel Humphery last July as head scientific advisor. She spent 2013-2014 at AZ. Atezolizumab (Genentech/Roche) and avelumab (Pfizer/Merck) are the only other ones worth mentioning. Assuming it is AZ's durvalumab, I hope VB111 leverages them to the fullest. AZ is now going to be 5th to market (best case).
Reaching Statistical Significance
I think we will be fine, but my only concern with the Ph3 rGBM trial is will it get below p=0.05. Dror seems to echo my concern. Their previous trials were against historical averages and comparing it to itself (where the p=0.048). That is so close. This is the only thing that gives me anxiety.
VBLT has been both lucky and smart
(1) I always wondered how Dror made the jump from fever to increased survival to immune response. They just got lucky with that one patient in the all comers trial who had a fever after a single dose and then continued to live. It was also brilliant that they were able to reconcile that observation.
(2) They seem to have good mouse models and/or they are being very careful with interpretation. It is hard to predict science outcomes, but it is easy to examine scientific rigor. VBLT is rigorous. I really like it.
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