Just passing along that I had just updated all my internal client systems to the latest SEP 12.1.6 MP1 (confirmed physically at the system, reboots are done)and on a system I am also going to do a Win 10 upgrade on, the Media Creation Tool (which I use the "upgrade this PC now" option) says that SEP is not compatible and forces me to uninstall it, giving me no choice about bypassing this. This system is Wiondows 8.1 Pro.
Yet on a clean install Win 10 Enterprise system built today using the ISO file via DVD media to build it, I was able to install SEP 12.1.6 MP1 full install (via setup.exe package instead of Remote Push from SEPM), it installed fine and LU ran fine. Upon reboot I"m not yet seeing it talk to SEPM though but on my SEPM machien I had accidently enabled two discontiguous networks via two NIC's so maybe this client is chasing after the wrong IP address or something. I'll give that some time, but the main point is that install went fine.
So not sure what to say, but it appears Microsoft is not up to date on their app compatibility, and the Enterprise ISO one didn't seem to have a problem. Both are build 10240.