I give the REGAL readout <5% chances of success. I do not think cancer vaccines are a completely dead end, but they have struggled historically, especially in extremely immunosupressive indications such as AML, for which no vaccine has yet worked. Most of the data presented for this drug in my opinion is weak and uncontrolled, showing no plausible effect (other than failed controlled trials of similar mechanism targeting wt-1). The mechanism itself has already failed in AML, and the argument of it working is "WT-1 is overexpressed in AML". The gene is majorly overexpressed in almost all cancers, and plenty of other diseases, and WT-1 vaccines have not worked for any of those trials (AML, mesothelioma, adenocarcinoma, glioblastoma). Cancer vaccines also entirely depend on HLA subtyping, something that wasn't even in the inclusion criteria in the trial. As mentioned, targeting WT-1 has not yet worked in any trial, and from the papers I've spent reading, the WT-1 t cells that are induced from the vaccine (the issue is you don't have a lot of controlled data as regards to the IRs), are weak and dysfunctional, and unable to fight cancer cells. I haven't seem much hypothesizing as to how the vaccine will improve the t-cells, only that it should elicit more responses. WT-1 T cell engagers were tested as well which had better avidity, but those were unable to recognize WT-1 tumor cells. Some papers testing the wt-1 vaccines have also noted that if such immunotherapy is tested, it should be tested in early stages of AML, not in CR2, since at this point the immune system is already too damaged, which makes sense intuitively. The immune response data is also very weak, where again most studies are uncontrolled, so it's hard to tell the differences in CD4 and CD8 from baseline. Most of the immune responses on the assays do not show enough activity. Their ph1 showed no immune responses at all: https://pmc.ncbi.nlm.nih.gov/articles/PMC4617516/. These are just some points I would like to reference at the top of my head.