I think we're saying the same thing. The disease model itself is necessarily limited. Sure you have a molecule that hits the target, great. But the struggle comes from being able to get that molecule to target in vivo without causing toxic effects.

Maybe we're just missing on how we're using words. I don't see how having a better disease model necessarily gets you to a better place on this. Sure, you can get better SAR and can decrease the dose. But as you point out, dosage is not just a function of SAR.

Having better tox models seems like the highest value, albeit very difficult, route here. Which to me is a separate, more general, problem than a specific disease model.