I think it’s a combination of patent protection (many applications not issued yet); people misinterpreting data required to support approval (I suspect conditional approvals requiring confirmatory trials aren’t on peoples’ minds); a failure by investors to understand IO and what is required to activate T cells, how to overcome immune checkpoints without actually using checkpoint inhibitors, how to improve cancer antigen presentation in situ, and what’s required to upregulate MHC Class I and II; and a complete misread in how versatile Oncosec’s multigene platform can be.
It is now crystal clear that checkpoint inhibitors are only part of the solution for solid cancers. To improve efficacy you need to use combination therapies. But systemic administration would be far too toxic. Oncosec’s approach takes advantage of a tumor’s full repertoire of cancer antigens by priming T cells in the TME - that is an enormous advantage! And it is arguably the safest method to administer combination therapies. DNA-encoded genes that get expressed as cytokines, antibodies, antigens etc following electroporation of plasmids aren’t transiently produced like mRNA or what’s observed with systemic administrations of checkpoint inhibitors; they are manufactured by cells in a protracted manner. This slows down the retreat of antigen presentation and chemokines, delays Treg infiltration while CD8 cells accumulate intratumorally, and armors T cells by downregulating checkpoint molecules like PD-1, CTLA-4, etc. for an extended period of time.
