Biotech Values

[biomaven0]

once a drug gets reasonable efficacy with tolerable sized pills or subq injection or ... then further potency is generally of little importance

I agree that potency per se is not that important, but my impression is that ultra potent small molecules (single digit nM IC50's) tend to do better in practice. Not something I've ever looked at systematically, but very high potency is likely a proxy for selectivity - if the molecule fits the target "just right" then it tends to not fit other targets with similar structure as well as might a molecule with just an "OK" fit. A similar argument can be made on the tox side - all other things being equal, a smaller effective dose will be less likely to produce some unexpected liver toxicity or the like.

In this particular case with a "warhead," I have no clue whether higher potency will be better or not - could just as easily be worse, with more collateral damage limiting the tolerable dose.

Peter