M1231 is a first-in-class bispecific antibody–drug conjugate targeting MUC1 and EGFR, designed to internalize into tumor cells and release a hemiasterlin-related microtubule inhibitor payload.

A multiscale systems pharmacology model integrated in vitro internalization data, tumor growth inhibition in MUC1-expressing xenograft models, and target-mediated drug disposition modeling in cynomolgus monkeys, with allometric scaling to predict human pharmacokinetics and tumor response.

Simulations predicted tumor stasis beginning at 2.4 mg/kg every three weeks and maximal regression at 4.3 mg/kg Q3W, informing dose selection for the ongoing first-in-human clinical trial (NCT04695847).

Hemophilia B is a genetic bleeding disorder caused by deficiency of Factor IX, leading to impaired clot formation and recurrent bleeding episodes.

To support the development of adeno-associated virus (AAV)–based gene therapy to restore Factor IX production, a mechanistic quantitative systems pharmacology (QSP) model was established that integrates a minimal physiologically based pharmacokinetic (PBPK) description of systemic and hepatic biodistribution with intracellular processes such as receptor binding, endocytosis, nuclear transport, and transgene expression.

Calibration with preclinical and emerging clinical data enabled quantitative prediction of Factor IX exposure–response and informed dose selection, providing a scalable translational framework adaptable to other AAV serotypes and liver-directed gene therapy programs.