MIDI completely dropping after 20 mins

I’m having to restart Cubase 8.5 every time in order to get it back online again

Using and M-Audio code 49 USB 2.0 - firmware updated on everything

Any ideas or tweaks to get this working without dropping and having to restart?

If you are on Windows it could be the power scheme that needs tweaking. Have a look at the advanced power settings for USB in Windows.