Using Systems Pharmacology Modeling Approaches to Guide Preclinical Animal Studies


John M. Burke, Applied BioMath

Asawari Samant, MathWorks

Inventing and developing safe and efficacious drugs is a difficult task, especially for co-modulation proteins that regulate the immune response for chronic autoimmune diseases. For example, there must be adequate target coverage to dampen the immune response, but not so much as to essentially shut off the immune system. The development of a bispecific biologic that targets two different co-modulation proteins expressed on cells is even more complex. In this webinar, we apply systems pharmacology techniques to predict the therapeutic window in cyno monkeys for this bispecific biologic.

In the second half of the webinar, we will demonstrate how SimBiology can be used to implement systems pharmacology approaches within the context of this bispecific biologic example.

Highlights include:

  • Building and characterizing a mechanistic model for bispecific biologics
  • Exploring dosing strategies to achieve response in the therapeutic window

About the Presenters: 

John M. Burke, PhD, is President, CEO and Co-founder of Applied BioMath, LLC, a Systems Biology and Pharmacology company. Dr. Burke’s BS and MS are in Applied Mathematics, University of Massachusetts, Lowell. His PhD degree is in Applied Mathematics, Arizona State University, where he studied dynamical systems, singular perturbation theory, and control of signal transduction networks and protein expression. Prior to Applied BioMath, Dr. Burke joined Boehringer Ingelheim (BI), as Global Head of Systems Biology, where he started, developed and managed the Systems Biology and Pharmacology group, portfolio, strategy and tactics. At BI, his group supported over 100 projects in five years, and over 11 transitions into Development or Clinical Trials. Prior to Boehringer Ingelheim, he was a Sr. Fellow in Douglas A. Lauffenburger’s lab, Biological Engineering Department, MIT; Co-Scientific Director of the Cell Decision Processes Center, Systems Biology Department, Harvard Medical School; then Merrimack Pharmaceuticals.

Asawari Samant is a Senior Application Engineer at MathWorks. She has a B.S. and M.S. in chemical engineering. At MathWorks, she primarily supports the pharmaceutical and biotechnology industry, and the computational biology sector.

Start Date: Feb 3, 2015 08:00

Quantitative systems pharmacology modeling (QSPM) approach provides biological insights and predicts optimal drug properties for dual targeting approaches for two immuno-oncology therapeutics

Biotech and Pharma are increasingly using quantitative systems pharmacology modeling (QSPM) approaches to help answer complex, critical Go/No-go decisions in R&D. Dr. John Burke will discuss the: • Value of QSP approaches • A QSP industry case study The case study entails developing and interrogating a QSPM of PD-1 and TIM-3. The QSPM provided: • Biological insights by predicting why dosing regimens are quite similar for two therapeutics targeting PD-1 that have affinities that differ by several orders of magnitude • Best-in-class profile predictions for PD-1 and TIM-3 dual antagonists This webinar is ideal for scientists in R&D who want to learn more about how to leverage QSPM to shorten timelines, lower cost, and increase the likelihood of developing best-in-class drugs. Speaker Info: John M. Burke, PhD Co-Founder, President, and CEO john.burke@appliedbiomath.com Prior to co-founding Applied BioMath, Dr. Burke was an Associate Director, Head of Systems Biology at Boehringer Ingelheim where he started, developed and managed the Systems Biology group, portfolio, and strategy. Prior to Boehringer Ingelheim, Dr. Burke was at Merrimack Pharmaceuticals, Co-Scientific Director of the Cell Decision Processes Center, Systems Biology Department, HMS, and was a Sr. Postdoctoral Fellow in Douglas A. Lauffenburger’s lab, Biological Engineering Department, MIT. Dr. Burke holds a PhD degree in Applied Mathematics from Arizona State University.

Start Date: Apr 5, 2016 12:45

Exploring ADC Pharmacokinetics using QSP Modeling Strategies

The Pharmacokinetics (PK) of ADC therapeutics typically show a discrepancy between the PK of total antibody and that of conjugated antibody, carrying one or more payload molecules. This discrepancy is often attributed to deconjugation, however recent evidence suggests that the underlying mechanisms may be more complex. In this webinar, Dr. Apgar will present how quantitative systems pharmacology modeling approaches provide biological insights into the impact of drug-to-antibody ratio and the resulting changes in molecular properties on overall PK and relative payload disposition as observed in preclinical and clinical studies. This webinar is ideal for scientists interested in how computational models can be used to design novel ADCs and to optimize the discovery and development of existing ADCs. Featured speaker: Joshua Apgar Co-Founder and CSO Applied BioMath Before co-founding Applied BioMath, Dr. Apgar was a Principal Scientist in the Systems Biology Group of the Department of Immunology and Inflammation at Boehringer Ingelheim Pharmaceuticals. Josh holds a PhD from MIT in Biological Engineering where he worked on experiment design for Systems Biology, focusing on the identification of tractable experiments that could allow for the estimation of unknown parameters and reveal complex mechanisms in signal transduction networks.

Start Date: Sep 13, 2017 08:30

Quantitative Modeling & Simulation Approaches: Driving Critical Decisions from Research through Clinical Trials

Quantitative Systems Pharmacology (QSP) is a mathematical modeling and engineering approach to translational medicine that aims to quantitatively integrate knowledge about therapeutics with an understanding of its mechanism of action in the context of human disease mechanisms. QSP approaches de-risk projects, accelerate the development of best in class therapeutics, and reduce late stage attrition rates. This results in helping industry save money, accelerate timelines, and make better therapeutics, ultimately improving patients’ lives. In this webinar, two case studies will be discussed to highlight how QSP efforts in rheumatoid arthritis have accelerated the discovery and development of best-in-class therapeutics, and impacted critical decisions, in the continuum from preclinical exploration to clinical research. Specifically, we will show how QSP impacts: Biological understanding, Lead generation, Clinical candidate selection, IND support, and clinical trial go/no go decisions from industry. This webinar is ideal for scientists and decision makers in R&D who want to learn more about how to leverage QSP to provide quantitative guidance for their drug discovery and development.

Start Date: Nov 7, 2017 09:00

How a Good Regulatory and Computational Strategy Helps Avoid Common Pitfalls

The development of New Chemical and Biological Entities is becoming more and more challenging. Most people agree that the lower hanging fruit has been picked. However, there are steps that companies can take to maximize their chances of success. Drug development 101 requires that companies develop a Target Product Profile (TPP) and a Regulatory Strategy, and yet many companies are failing in these endeavors, or are leaving them out of their development programs altogether. In this webinar targeted to scientists and project leaders in research and development, Dr. Lorna Speid will discuss and present examples of how to develop the Regulatory Strategy. Dr. John Burke will parallel these examples with case studies on how Model-Aided Drug Invention can support and guide such a regulatory strategy.

Start Date: Mar 4, 2018 09:00