Line6 UX2 and Catalina issues

You may have an issue with some other third party software that is installed on your Mac. Run EtreCheck and give it "Full Disk Access" so the report includes more details which may provide more clues. Post the report here using the "Additional Text" icon which looks like a piece of paper.

I am not familiar with most of the software installed. I'm not a macOS software expert so I hope another contributor will chime in regarding your third party software.

Most contributors will tell you that you should uninstall the VPN software because it is not making you secure. If you need a VPN to connect to a business, then usually the business will have their own dedicated VPN solution to use. Otherwise most VPN offerings are really only useful to make you appear to be operating in another region. This software may also be interfering.

The WD proproprietary software should be unnecessary unless you have WD SSDs where you are utilizing the SSD's built-in hardware encryption since your connected WD drives are using native Apple file systems.

Make sure all your third party software is completely up to date.

The one item of concern is the "Case Sensitive" file system being used on one of your external WD drives. I'm not sure how you are utilizing this particular WD drive, but most people should not be using a Case Sensitive file system. Apps (including Apple apps) may have issues with a Case Sensitive file system because the developers of the apps are not expecting it so do not test their apps under those conditions. Plus you may encounter issues trying to transfer files from a Case Sensitive file system back to a non-Case-Sensitive file system because you may end up with multiple files which will appear with the same exact name on the non-Case-Sensitive file system. For example the following file names are unique on a Case-Sensitive file system, but would give you errors for duplicate file names on a non-Case-Sensitive file system since a non-Case-Sensitive file system does not distinguish between upper & lower case characters. Unfortunately the only way to change the file system is by erasing the drive and restoring the contents from a backup.

All of these names would be considered identical on a non-Case-Sensitive file system:

• MyFile
• myfile
• Myfile

While your internal boot drive appears to be operating at a decent speed, the internal hard drive this old may be starting to wear out or even failing. Run DriveDx and post the complete text report here using the "Additional Text" icon which looks like a piece of paper. I have seen a worn out drive have intermittent performance issues which perhaps may enough to cause issues with your audio apps.

You should disconnect all unnecessary external devices in case one of them is causing a problem.

You should always have frequent and regular backups of your computer and all external media (including the cloud) which contains important & unique data.

Keep in mind a drive can appear healthy in the DriveDx summary but still have problems. Seeing the actual health information on the drive may reveal potential issues that have not yet gotten severe enough to trigger a "Warning" message in DriveDx. Granted this is a long shot, but I would be happy to review the drive's health report for you.

Well since you don't seem to want to post the DriveDx report, then I will have to assume the drive is causing your problems. I suggest you install macOS to an external USB3 SSD to bypass the internal hard drive. Unfortunately this may not be definitive since your setup may be more sensitive to possible USB issues while booting from USB (not a problem for most people, but may be for this test with your setup & what you are trying to resolve). It would also be best to unmount the internal drive when booting & testing from the external to minimize the internal drive from interfering during testing how the external USB3 SSD performs.

Maybe another contributor will have some other ideas especially regarding your installed software or this device, but at this time with the information presented I am going with a bad drive assuming you already tried uninstalling the VPN and WD software and disconnected all external devices except the one you are having issues with in case there is a compatibility issue between devices. Connect the UX2 directly to the Mac. Also you can try connecting the UX2 to a different port if possible in case the port is bad (not really sure what connections are used with UX2) and try using different cables.