Most of his enemies are criminally insane, and locked in the Miskatonic Mental Institution (a play on Arkham Asylum, and H. P. Lovecraft's Miskatonic University in the city of Arkham).
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In one of the Supreme earlier stories, he teams up with Darius Dax to switch Supreme and Professor Night's minds, but the duo manage to reverse the effect and switch the minds of the two villains.