Line 6 Helix Native + Cubase 10.5 suddenly doesn't work anymore.

working fine in cubase here - if it crashes Premiere then, yes, I think it’s a Helix issue. Must be something corrupted in your install. Probably worth an uninstall/reinstall as a next step. Not sure if the uninstall will clean up the corruption but worth a try. If not then it’s a case of working out what is actually corrupted.