Poor target engagement or linkage to disease or disease phenotypes | Compounds are targeted at molecules that are not relevant in the pathogenesis of the human disease condition |
Linkage of target with human genetics data relevant for disease in question Perform GWAS, rare functional mutational, Mendelian randomisation or other biomarker analyses Pharmacodynamic biomarker to assess engagement of target molecule of interest
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Dose of drug limited by characteristics of compound or target tissue | Once in humans, because of safety concerns or undesirable pharmacokinetic properties, the dose cannot be optimised |
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Poor patient selection | COPD is a heterogeneous disease and as such unselected patients are likely to have variable responses to treatment, diluting the effects of the drug |
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