Category 2• Complex pharmacology underlying Shh and catenin signaling and the proposed mode of action resulting in pilomatricoma raised concerns of over- or under-estimating human risk• Potential off-target effects• Potential hormonal effects (increase in FSH and LH)• Discussion on safety margins not sufficient• Experience with drug class insufficient to aid prediction for the compound. The gene discussed is BRD2; the disease is pilomatrixoma.