Yes, and if they can keep the project healthy, we can expect it to continue to increase in speed, in fact according to the authors the speed improvements are just starting.
I just tried it yesterday on one Django project. The DB migration failed. It seems that when doing DB migration, Django actually looks for .py files which don't exist anymore with nuitka.
Yes; any framework or tooling that relies on runtime imports (eval is OK, just not eval-from-file) is not going to work with rather a lot of compiled-python programs.
It's possible to build shims that support "import module if running interpreted python; just point to already-loaded/compiled code (or eval a string, ew, but if you must) if not", but many large projects do not do that. It is likely not too painful to implement/send a PR for though.