This is an interesting idea. I also really really like SirPeebles's idea of having them be worth victory points if the pile runs out.
I think you will have to do some funky wording antics to get it precise though. Maybe something like:
When you play this, execute the text on the top card of the Polymath supply pile.
When you play a Polymath card while this is the top card of the Polymath supply pile, +$3, +1 buy.
So say you play the $3/buy card (call it A) while the 2 cards/2 actions card (call it B) is on top. Then you say "I played A, so I execute the top card of the Polymath pile. That says when I play it (B), to execute the text on the top card of the Polymath pile, but I can ignore that because I didn't play B. Then it says when I play any Polymath card, which I just did, while that is the top card of the Polymath pile, +2 card, +2 actions. So I'll do that. Now I finish resolving the text I was reading on A. It says When I play a Polymath card while this is the top card of the pile, +$3, +1 buy, but it's not the top card of the pile, so I ignore it."
Alternatively, you might be able to have:
[horizontal line]
When you play a Polymath card while this is the top card of the Polymath supply pile, +$3, +1 buy.
Then that just becomes a general thing that happens whenever the cards are in the supply. But having a horizontal line with no text above it (something which I think Band of Misfits needs) looks awkward, so I'm not sure if that's desirable.
And then I think Polymath would have to be a new card type, since "Polymath card" is not something that's already defined. And I think each distinct copy would have to have a different name. I'm not sure about that though, but I can't think of any cards with the same name but different effects.