Etentamig is a BCMA x CD3 bispecific antibody in development for RRMM and AL amyloidosis. The webinar will showcase the MIDD strategies that guided key decisions and advancements: (1) optimal dosing regimen selection for RRMM, including step-up dosing via exposure-response and PK/IL6/CRS analyses; (2) demonstration of no DDIs via an IL-6 PBPK model; (3) repriming/restart therapy guidance after dosing delays using PK simulations; and (4) interplay between sBCMA, free, and total PK using a semi-mechanistic PK/PD model to recommend free PK assay only in future studies. Overall, MIDD successfully guided optimal dosing regimen selection and key regulatory decisions for etentamig. The MIDD Webinar Series, coordinated by Yash Kapoor and Fulya Akpinar Singh, is a series of webinars focused on shaping the future of drug development and regulatory decision-making sponsored by the ISoP Education Committee. Topics range from MIDD approaches in regulatory submission to pharmacometrics topics that are at the core of model development.

The ICH M15 Guideline “General Principles for MIDD” stresses the importance of performing model evaluation targeting the Question of Interest (QoI) that model is intended to help to answer. In this presentation we elaborate on how reference corrected visual predictive check (rcVPC) methodology can be used for this purpose. The rcVPC can provide an efficient and more easily communicable tool to validate models, increasing confidence in model-informed decision-making among broader, non-modeling stakeholders. The MIDD Webinar Series, coordinated by Yash Kapoor and Fulya Akpinar Singh, is a series of webinars focused on shaping the future of drug development and regulatory decision-making sponsored by the ISoP Education Committee. Topics range from MIDD approaches in regulatory submission to pharmacometrics topics that are at the core of model development.

Pediatric dose optimization is constrained by small cohorts and sampling limits. We applied Bayesian Forecasting to select the RP2D for pediatric patients with ALK-fusion tumors. An established PopPK model using adult data as prior in combination with real-time PK monitoring during Cycle 1 guided dose confirmation and/or adjustments. Doses were selected to match the adult steady-state therapeutic exposures. Model‑predicted doses achieved target exposure without adjustment in all 14 patients ≥20kg; 4/5 patients

A model-based dose selection and pharmacokinetic (PK) bridging approach was applied to support development of pembrolizumab SC (pembrolizumab with berahyaluronidase alfa for subcutaneous administration) from intravenous (IV) administration. Methodology, results and conclusions will be discussed in this presentation. The MIDD Webinar Series, coordinated by Yash Kapoor and Fulya Akpinar Singh, is a series of webinars focused on shaping the future of drug development and regulatory decision-making sponsored by the ISoP Education Committee. Topics range from MIDD approaches in regulatory submission to pharmacometrics topics that are at the core of model development.

This talk explores how model-informed drug development (MIDD) can evolve from a supportive tool into a central pillar of clinical strategy. Using the development of AZD8233—a novel PCSK9 antisense oligonucleotide—as a case study, the presentation will walk through how modeling guided key decisions from Phase 2b to Phase 3, including trial design, dose optimization, and cardiovascular risk prediction. The MIDD Webinar Series, coordinated by Yash Kapoor and Fulya Akpinar Singh, is a series of webinars focused on shaping the future of drug development and regulatory decision-making sponsored by the ISoP Education Committee. Topics range from MIDD approaches in regulatory submission to pharmacometrics topics that are at the core of model development.

IVIG co-administration with monoclonal-antibodies/bispecifics is common across autoimmunity, immunodeficiencies, and transplantation. These therapies undergo FcRn-mediated recycling, raising potential for PK-PD interactions. Mechanistic IgG-disposition model utilized to investigate how IVIG dose/timing, and IgG dynamics influence IgG behavior and PK/PD outcomes. Model well-described total/endogenous-IgG kinetics across autoimmune/transplantation. It recapitulated reduced tesidolumab exposure with IVIG in transplantation, explaining associated PD alterations. Model examined IVIG supplementation in multiple-myeloma receiving teclistamab, and rituximab-IVIG co-therapy for transplant desensitization. Simulations revealed IVIG co-therapy alters mAb PK-PD depending on IVIG-regimen, IgG-pool and exposure-response-relationship of the mAb. Model provides mechanistic framework for MIDD and prospective management of IgG interactions. The MIDD Webinar Series, coordinated by Yash Kapoor and Fulya Akpinar Singh, is a series of webinars focused on shaping the future of drug development and regulatory decision-making sponsored by the ISoP Education Committee. Topics range from MIDD approaches in regulatory submission to pharmacometrics topics that are at the core of model development.

This webinar will focus on the PKPD models developed and used end-to-end to design and execute a Phase 1 study for a first brain-penetrant PROTAC ARV-102. Core PKPD models were developed using nonclinical data and included allometrically scaled PK parameters and animal-derived PD parameters for target engagement. Model simulations were used to select a dose range for the first in human study and the PKPD models were updated to refine the dose response. The iterative modeling-experimentation resulted in a successful Phase 1 study and illuminated important translational relationship of PROTAC PKPD between animals and humans.

Quantitative Systems Pharmacology (QSP) is increasingly applied in MIDD frameworks and regulatory interactions, though challenges remain in ensuring transparency and credibility. This webinar will share insights from the group’s work, including considerations on virtual populations, regulatory submission examples, proposed minimum evaluation criteria, and ongoing challenges highlighting areas in need of further regulatory guidance.

The MIDD Webinar Series, coordinated by Yash Kapoor and Fulya Akpinar Singh, is a series of webinars focused on shaping the future of drug development and regulatory decision-making sponsored by the ISoP Education Committee. Topics range from MIDD approaches in regulatory submission to pharmacometrics topics that are at the core of model development.

The MIDD Webinar Series, coordinated by Yash Kapoor and Fulya Akpinar Singh, is a series of webinars focused on shaping the future of drug development and regulatory decision-making sponsored by the ISoP Education Committee. Topics range from MIDD approaches in regulatory submission to pharmacometrics topics that are at the core of model development.