ONCS vs. Advaxis:
1) Advaxis uses gene modified live bacteria. Bacteria is rendered "harmless". However, it still wakes up the immune system (our innate system is coded to get revved up when it sees bacteria)
2) Bacteria is also embedded with DNA plasmid that encodes single target antigen. This antigen is a "well known" antigen for a specific cancer. They can target different antigens for different cancers.
3) Results from Advaxis HPV trial:
- 11% ORR
- additionally about 30% had "stable disease".
This is the characteristic pattern of responses from vaccines where very little actual visible shrinkage. But more so "stable or slowing of disease". The 11% ORR is at least better than nothing.
4) Toxicity - relatively mild. Fever, chills and cytokine release syndromes from live bacteria infusion. Seems more so than Tvec virus. But overall manageable. Requires antibiotic to eliminate the live bacteria after.
5) It is CLEAR the company sees no future in monotherapy (with the less than so so results above). Therefore, they have immediately changed strategy, hired a reputable new CMO and pushing hard for combination PD1 trials. They are starting 2 combo trials. One with Merck. One with MedImmune. Like Tvec and ONCS, they are hoping for big increase in responses from combination.
This brings me to the crux. I repeat - very very few vaccines lead to obvious, visible, regression of tumors. Traditionally, vaccines have led to slowing of disease, or making cancer come back slower after surgery (cutting it out). But very few actually cause tumors to disappear. Tvec & ONCS have very clear shrinkage of tumors. Actual shrinkage has only been reliably seen with CAR-T and PD1.
As to whether combo Advaxis+PD1 will be as good or better than Tvec/Immunopulse + PD1, since they have no human data, the only clue we can use is their mouse data.
Mouse data:
(a) We know ONCS mouse data shows 100% complete regression with Immunopulse + PD1
(b) Advaxis+PD1 yields 20% complete regression (compare that to Immunopulse 100% regression).
The 20% vs 100% in mice should give you an idea as to comparative efficacy.
