The current state of TB science suffers from some critical weaknesses. The Modeling & Simulation Working Group under the CPTR Regulatory Science consortium is addressing some of these limitations and developing new TB drug regimens using pooled data from legacy clinical trials performed by CPTR Drug Coalition member companies and other sources. Additional data on relevant biomarkers (e.g. laboratory tests, imaging parameters, microbiologic assays, etc.) and clinical endpoints will be progressively incorporated into the models with the goal of informing clinical trial design. This approach will be used to characterize and quantify natural disease progression, placebo and drug effects, and inform dose selection as well as trial execution variables (e.g., patient discontinuation rates, dosing schedules, compliance, specific design, etc.) from multiple trials using patient-level data. Models can increase efficiency and decrease risk of errors in drug development decisions by overcoming the complexity and uncertainties of the disease-drug-treatment interaction. This Working Group supports a related set of work streams that directly or indirectly address some of the current limitations in combination drug development, including an empirical drug-disease-trial model, a physiologically based pharmacokinetic model on the Simcyp platform, an in vitro hollow fiber system model, a population PK-PD model, a mechanism based systems pharmacology model, as well as, QT assessment and interpretation in the context of new combination TB drug development.