How does this work? Does it run the x86_64 version of Wine in Box64? My understanding of wine was that it just translates API calls, shouldn't it work on any ISA then? (Or is most of a program / game math and that stuff would fail?)
You can't run amd64 without something like Box64 because Wine is not an emulator, so it doesn't interpret or rewrite the instructions to aarch64.
You can use Box64 on other ISAs if you implement the necessary translation code. I believe this is what's being done to run games on RISC-V, but I'm not 100% sure. Good ol' qemu-static would also do the job if Box64 isn't compatible (yet), but that's running the entire application in a foreign architecture so the overhead would be a lot more significant.
If what you describe is being done, it's being done by Box64. I don't know enough about aarch64 to know what ARM64X and ARM64EC do, though. I can find [a Github comment](https://github.com/ptitSeb/box64/pull/858#issuecomment-16057...) where one of the authors states that the goal is to implement ARM64EC, but I wouldn't know what the status is on that.