MacOS Big Sur 11.6 (20G165)
Safari Version 15.0 (16612.1.29.41.4, 16612)
Adobe Acrobat DC 21.007.20096

Safari no longer supports opening PDFs in Acrobat, rather than the browser. A high-level tech support at Adobe screen-shared on my computer and couldn't find any way to set it so that PDFs would open in Acrobat. Help files on Adobe's help site refer to an older version of Safari, which had preferences different than the current version (see attached screen shot of current Safari preferences).