14/04/2023
A QSP model supporting dose justification for the novel PARP1-selective inhibitor AZD5305 was presented at AACR 2023 annual meeting.
AZD5305 is a potent and selective PARP1 inhibitor and trapper which is hypothesized to improve therapeutic index over first generation nonselective PARP inhibitors. In a collaborative effort between M&SD and AstraZeneca scientists a quantitative systems pharmacology of PARPi mechanism-of- action was developed and applied to explore dose-dependent antitumor activity of AZD5305 across a selection of xenograft models with different homologous recombination repair (HRR) status. As result, the model was used to predict an effect at clinically relevant exposure observed in the phase I clinical study PETRA. Model-based simulations indicated near maximal efficacy at clinical doses equivalent to 1 mg/kg exposure in xenograft models.
