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The Delaware Valley Drug Metabolism: Discussion Group (DVDMDG) presents an in-person symposium “Project Optimus and Oncology Drug Development” on Thursday, November 16.

8:00 – 9:00 am

Registration and Breakfast

9:00 – 9:10 am

Welcome and Introduction
Yan Zhang, Ph.D., Senior Director, DMPK/Clin Pharm (Nuvation Bio)
Christopher Kochansky, Director, DMPK, Drug Discovery Sciences (Exelixis)

9:10 – 9:55 am

Pragmatic and Holistic Approach for Dose Finding and Optimization in Oncology Drug Development — A Clinical Pharmacology Point of View on Project Optimus (remote presentation)
Jiang Liu, Ph.D., Associate Director, Division of Pharmacometrics, OCP (FDA)
Abstract: Efficient dose finding and optimization in the general population and an individual patient have always been a critical issue of drug (including oncology drug) development. With advances in cancer biology and new molecular targeted agents and immunotherapies, a pressing need for an improved oncology drug dose finding and optimization strategy has been highlighted, as demonstrated particularly by the recent Project Optimus from the FDA. The new strategy will require a multi-disciplinary collaboration to integrate all available nonclinical and clinical information, including pharmacokinetic (PK), pharmacodynamic (PD), activity or efficacy, safety and tolerability, and patient-disease-trial factor impacts and an understanding of dose- and exposure-response relationships for safety and efficacy. This presentation will provide an overview of the current landscape of dose finding and optimization in the oncology drug development. A pragmatic and holistic approach integrating the totality of evidence at different stages of drug development for dose selection and optimization for general or specific populations will be discussed and illustrated using representative case examples.
Dr. Jiang Liu is the Associate Director for Therapeutic Reviews of the Division of Pharmacometrics, Office of Clinical Pharmacology, Center of Drug Evaluation and Research, at the U.S. Food and Drug Administration. Dr. Liu received his Ph.D. in pharmaceutical sciences and Masters in statistics from the University of Florida. He joined the FDA as a pharmacometrics reviewer more than 14 years ago. Dr. Liu had also served as a QT-IRT scientific lead for three years and a pharmacometrics team leader for four years before taking his current role. He is overseeing pharmacometrics review activities focusing on oncology, immunology, rare diseases, etc.

9:55 – 10:40 am

QSP Approaches to Assessing Oncology Drugs
William Jusko, Ph.D., PKPD Modeling Courses and Consultant Services, Distinguished Professor of Pharmaceutical Sciences (SUNY)
Abstract: The assessment of chemotherapeutic effects using pharmacokinetic and pharmacodynamic models spans a range of experimental approaches utilizing cell cultures and animal xenografts to studies in humans monitoring tumor sizes and patient survival. Cell culture systems, particularly with inclusion of cell cycle kinetics, has allowed discernment of mechanisms of drug action (irreversible and reversible), and elucidation of multiple steps in drug action. Transit compartment models are particularly useful for accounting for time-dependent processes in both cell and xenograft responses. Semi-mechanistic Psi parameters have proven useful for quantifying the nature of dual and triple drug interactions. These methods are contained in network models that help analyze the plethora of data harvested by inclusion of diverse genomic and proteomic measurements. Our studies utilize such QSP approaches to assess the joint effects of gemcitabine and second drugs in treatment of pancreatic cancer.
Dr. Jusko is SUNY Distinguished Professor & former Chair of Pharmaceutical Sciences at the University of Buffalo. He received his BS in Pharmacy (1965) and PhD (1970) degrees from Buffalo. He then served as Clinical Pharmacologist at the Boston VA Hospital and Assistant Professor of Pharmacology at Boston University. He returned to Buffalo in 1972 as Director of the Clinical Pharmacokinetics Laboratory and Assistant Professor. He received the Doctor Honoris Causae from the Jagiellonian University in Poland (1987) and from the University of Paris Descartes (2015) and has many other awards including the 2018 Oscar B Hunter Career Award from ASCPT and the 2020 Distinguished Pharmaceutical Scientist Award from AAPS. He serves on the Editorial Boards of 7 journals and is former Editor-in-Chief of JPKPD. His research covers clinical, basic, and theoretical PK/PD of diverse drugs, particularly immunosuppressants, anti-diabetics, anti-cancer drugs, and antibodies with over 650 publications.

10:40 – 11:00 am

Coffee Break

11:00 – 11:45 am

Oncology Dose Optimization Readiness – a drug development perspective
Sandra Visser, Ph.D. VP, Head of Oncology Clinical Pharmacology Modelling and Simulation GSK
Abstract: FDA’s Project Optimus aims to reform oncology dose optimization. This initiative marks a watershed moment for oncology drug developers to rethink the drug development paradigm. What adaptations does pharma need to make to change the dose-optimization paradigm? What challenges do need to be overcome? We at GSK took a holistic look at what we need to be doing to get ready for Project Optimus, ahead of the release of the draft FDA guidance. We focused on the following: a) understand expectations of Project Optimus on evidence generation across R&D functions; b) develop a dose optimization framework and guidance for projects teams; c) clarify the value drivers across the oncology portfolio from greater dose optimization and d) highlight operating model implications across key dimensions such as governance, processes, and capabilities. This project highlighted that improving dose optimization is essential to bring safe and effective medicines to patients and will bring Oncology Development closer in line with clinical development in other therapeutic areas. Investments in capabilities and analytics and optimization of the process of data generation, cleaning, and programming, embedded in a clear accountability framework are needed to allow for efficient and sufficient data generation with rapid decision-making around dose optimization. The costs for increased evidence generation in early stages of development are expected to be offset by a more streamlined registrational program with further synergies for assets with indication expansion and combinations.
Sandra Visser is VP, Head of Oncology Clinical Pharmacology Modelling and Simulation at GSK and currently seconded to the global development governance board secretariat. She led the task force to get GSK’s Oncology Development ready for Project Optimus. She is passionate about application of clinical pharmacology and model-informed drug discovery and development strategies in drug discovery and development to drive project and portfolio value and to improve R&D decision making. Sandra received her PhD in quantitative pharmacology from Leiden University in The Netherlands, worked and lived in Sweden (AstraZeneca) before coming to the United States to join Merck in 2013.

11:45 – 1:00 pm

Lunch / Networking

1:00 – 1:45 pm

QSP, a Key Enabler for Project Optimus
Birgit Schoeberl, Ph.D., VP, Global Head, Translational Modeling & Simulation and Data Science (Novartis Institutes for BioMedical Research)
Abstract: In this talk, Dr. Schoeberl will discuss how Quantitative Systems Pharmacology (QSP) and semi-mechanistic models will be a key enabler to inform dose finding and optimization by leveraging nonclinical and clinical data in oncology. She will also discuss some examples and lay out a vision for the future.
Dr. Birgit Schoeberl is the Global Head of Modeling and Simulation, PK Sciences at Novartis Institutes of Biomedical Research (NIBR) in Cambridge MA. Her team uses machine learning, computational fluid dynamics, QSP and PBPK modeling to address drug development questions from discovery to approval. Prior to joining NIBR, Dr. Birgit Schoeberl spent time at GNS Healthcare as SVP of Scientific Value using Bayesian Network Inference to build models directly from data to identify causal disease drivers or to identify predictive biomarkers. She was a founding scientific team member of Merrimack Pharmaceuticals where she applied different modeling techniques to inform drug discovery and held various leadership roles. Before leaving Merrimack Pharmaceuticals she was responsible for Discovery and the early clinical development and part of the executive leadership team.

Dr. Birgit received her Chemical Engineering degree from the Technical University in Karlsruhe, Germany, and Ph.D. in Biological Eng. from the Max Planck Inst. for Dynamics of Complex Technical Systems in Magdeburg. She received postdoctoral training in the Biological Engineering laboratories of Douglas Lauffenburger and Peter Sorger at MIT.

1:45 – 2:30 pm

Top 10 Trends in Oncology Drug Development in the Era of Project Optimus
Julie Bullock, Pharm.D., Senior VP, Head of Clinical Pharmacology & Translational Medicine (Certara, Integrated Drug Development)
Abstract: Since the launch of FDA Oncology Center of Excellence Project Optimus initiative, the expectations for oncology dose finding and development have drastically changed. In this session, an introduction to the Project Optimus initiative including why now and what to expect will be presented followed by discussion of 10 trends to be aware of in this rapidly changing landscape.
Dr. Bullock is currently a Senior Vice President with Certara Drug Development Solutions (consulting division of Certara). She has over 20 years of drug development experience and is a recognized drug development scientist with scientific and regulatory expertise focused in the therapeutic areas of oncology/hematology and coagulation. Julie has extensive experience in all development phases including regulatory interactions with major global health authorities (FDA, EMA, PMDA), due diligence, design of clinical development plans, pediatrics, dose-finding strategy and streamlining development for breakthrough therapies and accelerated approval. Julie is a Key Opinion Leader on the FDA’s Project Optimus (oncology dose finding) initiative and has provided risk-assessment and tactical dose justification support for over 100 early and late-stage oncology assets since the launch of Project Optimus in 2022.

In her current role, Dr. Bullock supports a global team of clinical pharmacologists with regulatory strategy and drug development experience who provide program level and strategic support to Biotech and Pharma company portfolio programs.

Prior to her role at Certara Dr. Bullock was a Team Leader for the Hematology/Oncology review team in the Office of Clinical Pharmacology at the Center for Drug Evaluation and Research at the FDA. Julie’s FDA career spanned 10 years where she contributed to over 14 new molecular entity NDA/BLA filing applications, multiple supplemental NDA/BLA applications and countless IND related submissions submitted to the hematology/oncology division. Dr. Bullock received her Doctor of Pharmacy from Drake University and completed a drug development fellowship with the State University of New York at Buffalo and Novartis Pharmaceuticals.

2:30 – 2:50 pm

Coffee Break

2:50 – 3:30 pm

Roundtable Discussion
All speakers

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