This article kind of grinds my gears. I feel like there is an unstated assumption that people in pharma R&D are idiots and haven’t thought of this stuff.

Pharma companies care very much about off target effects. Molecules get screened against tox targets, and a bad tox readout can be a death sentence for an entire program. And you need to look at the toxicity of major metabolites too.

One of the major value propositions of non small molecule modalities like biologics is specificity, and alternative metabolism pathways; no need to worry about the CYPs.

Another thing they fail to account for is volume of distribution. Does it matter if it hits some receptor only expressed in microglia if it can’t cross the blood brain barrier?

Also the reason why off targets for a lot of FDA approved drugs are unknown is because they were approved in the steampunk industrial era.

To me this whole article reads like an advertisement for a screening assay.