I am using a Librem 13v4 with Qubes 4.1. I flashed Pureboot 21 via USB with a precompiled image and injected SN. The BIOS functions and interacts with the librem key normally. After selecting boot I can decrypt the disk but while loading it crashes and the OS will not boot. The problem is solved by reverting to Pureboot 18.1.
I’m not able to reproduce that here on a L13v4 with Pureboot 20/21 - a previous install of Qubes 4.1 boots without issue here