The goal of this collaboration was to provide early quantitative decision-making guidance for the project team by developing and interrogating a quantitative systems pharmacology (QSP) model of the co-modulation inhibitory receptors PD-1 and TIM-3 in immuno-oncology. The QSP model was to explain why marketed anti-PD1s have such similar dose regimens despite very different Kds (MK-3475 (Pembrolizumab, Keytruda™): 2mg/kg Q3W, IV, Kd = 30pM and MDX-1106 (Nivolumab, Opdivo™): 3mg/kg Q2W or Q3W, IV, Kd = 3 nM) as well as predict optimal drug properties targeting PD-1 and TIM-3 in oncology for bispecific biologics as well as fixed-dose combinations (FDC). We also provided a bispecific versus FDC risk assessment.
- QSP model analysis predicted there would be diminishing returns on very tight binding biologics due to Target Mediated Drug Disposition (TMDD) that offsets potency
- QSP model analysis predicted there is no advantage between FDC, 2-2 bispecific, and 2-1 bispecific formats, which are predicted to be roughly equivalent in terms of dosing requirements