Thanks for digging into one! I had a project back on this back in my Probabilistic Graphical Model days with Simon Lacost-Julien (I believe this was my worst-ever grade in a course)... so I’ll defer to you on the mechanism.

I do know you're right that affinity/residence time and efficacy are separate axes. Bio is one of our sparsest regions (due to closed access papers, and our focus on core ML), so proposals there are more likely to have issues like this.

We've got some ideas on how to improve these issues, but I really appreciate you helping us by pointing this one out!