That's a bummer. Thank you very much for your help!

Oh, I just found this in the documentation: iPad and iPhone apps running on a Mac with Apple silicon can’t connect to external accessories using this framework. You may continue to link apps to this framework and run other features on Apple silicon. So it seems that I have no recourse? Would adding support for Catalyst address this problem? Originally, I only wanted to run my app on my Mac so that I can use Instruments with the external USB device connected. Using Instruments wirelessly on my iPad slows everything down to a crawl (wireless profiling is needed since I only have one port available in my iPad)

Using External Accessory framework? Yeah, that's correct. I'm not the one who worked on that part, but I see from the comments and code that it monitors iOS ExternalAccessory.framework for devices.

I was able to do it by creating a dummy Xcode project and modifying the scheme to target the executable of my application. If I enable Metal frame capture, then I can run the profiler without issues.