A large and rapidly growing number.
The largest commercial classes of multi-domain therapeutic proteins include the crispr (and similar) that drive gene therapies, and the chimeric antigen receptors (and similar) that drive cell therapies.
But lead optimization there look different than this page’s efforts.
Oh yeah good point on crispr and the antibody chimeras (which etanercept is)
I guess I imagine one of the highest order obstacle to protein therapeutics to be immunogenicity, which is really hard to design around for a de Novo protein