definiens: means a Validated Hit that has been approved by the Steering Committee after recommendation by the Collaboration Committee for further development or chemical optimization based on substantially demonstrating : 1 . preferably modulation ( e.g. activation or inhibition ) of an in vitro assay activity ( e.g. biochemical ' or cell based ) used for primary screening at a concentration of l.00 nM or less underprimaryscr, eeningconditions ; 2 . suitable bioavailabilitycharacteristics ba ~ ed qn'''pharmcokiQetit data .from three ( 3 ) groups of three ( 3 ) rats admi ~ istered oraUy''imdIV, 3 . suitability for medicinal chemistry ;, 4 . the absence of a Third Party intellectual property position known to either party ( without any obligation of diligence by either party ) that would, impede the development of a Validated Hit ; and 5 . selective modulation of an assay activity used for primary screening compared to other processes or targets reasonably selected for selectivity that is meaningful in regard to treatment ofCF . Preferably, such chemicals will be active against a target at a concentration at least, 10 fold lower than a given concentration where no meaningful modulation occurs of activity measured by a selectivity assay