Translating R&D concepts into confident decisions
QSP has enormous potential to improve biopharmaceutical R&D and inform decision-making across the drug development process. QSP combines computational modeling and experimental data to examine the relationships between a drug, the biological system, and the disease process. With the ability to leverage vast amounts of biological and pharmacological data, QSP enables the understanding of disease pathophysiology, to identify and test therapeutic strategies in virtual trials with virtual patients.
Certara has differentiated its approach to QSP by building robust, regulatory-ready software platforms for reproducible model development. Today, those platforms are available for immunogenicity, immuno-oncology, and next, neurodegenerative diseases. The software is available in proprietary and proven editor tool, with an easy-to-use interface, that delivers models and model results that are reproducible. This unique approach has been shared with US, EU and Japanese regulators, all committed to advancing the use of QSP in drug discovery, development and regulatory review.
Download QSP Fact SheetUnderstanding the Impact of Immunogenicity
Innovation in biologic development has led to a marked increase in the approvals of protein-based therapeutics for a range of diseases. Despite the success of biologics, immunogenicity (IG) or the tendency to trigger an unwanted immune response remains an inherent and major challenge.
In response to this challenge, Certara developed a software platform with support from the seven members of its QSP IG Consortium to predict the IG of biologics and its impact on efficacy and safety in diverse patient populations. Certara’s IG Simulator, built in a unique regulatory-ready platform supports decision-making from discovery through clinical. It can take FIH data to design Phase II/III trials, predict impact of disease and co-medication, extrapolate to new populations, and predict if IG can be managed by dosing.
The robustness of this groundbreaking model will facilitate compound prioritization and inform go/no decisions for biologics developers. Based on our work in IG, we have developed a new QSP platform for vaccines. The Certara QSP Vaccine Simulator is used to provide dosing recommendations across multiple patient populations for COVID-19, oncology, and RSV.
Advancing Combination Immuno-oncology Therapy
While Immuno-oncology has delivered on its promise for treating a wide range of cancers in targeted populations, the expansion of that success through combination therapy has been more elusive. QSP is well suited to address this challenge, by understanding and integrating the complex dynamic factors determining efficacy that can lead to better combinations and dosing regimens for a wider group of patients.
Working with a consortium of six leading pharmaceutical companies, Certara has developed a QSP IO Simulator that will enable exploration of different therapeutic combinations, even drugs using different modalities, within virtual populations. The Simulator incorporates compounds’ pharmacokinetics, target binding, and mechanisms of action as well as existing knowledge on the underlying tumor and immune system biology to predict clinical results for novel combinations, and complex biologics such as bi-specifics.
The Challenges of Neurodegenerative Disease Drug Development
Neurodegenerative diseases (ND), which includes >1,000 individual disorders, have a profound impact on society, including death and debilitation of millions of people. But ND has been the most challenging areas of development, with failure after failure, especially in Alzheimer’s Disease.
Recognizing the tremendous need, challenges and opportunity, Certara is developing a QSP platform for identifying and understanding quantitative interconnectivities of common biological pathways and networks and their potential for pharmacological exploitation in ND. This can lead to a better quantitative understanding of the interrelationships between dose, pharmacological effect, disease progression and clinical outcome within specific patient populations and aid in the identification of clinically accessible biomarkers that reflect disease progression.
QSP can leverage big data to enable the understanding of disease pathophysiology, for the dynamic interactions between drug(s) and a biological system and allow us to identify and test therapeutic strategies in silico. This enables the evaluation of the pharmacological potential of drug therapies through quantitative mechanistic relationships between administered dose, tissue drug concentrations, biomarkers and pharmacological response via integration of PBPK and QSP modelling.
Tackling the most complex challenges with consulting services
In its July 2020 workshop, the US FDA described this modeling & simulation technology as shifting from “justifying the value of QSP”—to “best practices” implementation.” QSP helps answer questions about novel compounds and modalities, combination therapy, initial dosing for first-of-its kind therapies, and other vexing development situations:
- In a given biological pathway, what are the best target and modality for pharmacological intervention to treat a disease?
- How can we improve the therapeutic effectiveness of an existing drug through combination therapy?
- Can we predict human response (dose) to a novel mechanism based on preclinical data?
- How can we better understand the underlying pathophysiology to identify druggable pathways?
- Can we predict the effect of a drug in a special population?
- How can QSP support translation, product differentiation and utility of biomarkers?
- Can we individualize dosing regimen based on patient characteristics?
- How can we optimize clinical trials by accounting for pharmacodynamics interactions with co-medications and genotypes?
Certara provides QSP consulting services and regulatory support to address the above questions in therapeutic areas including oncology, vaccines, neurology, CNS, hematology, autoimmune disorders, rare diseases, dermatology and gene therapy.
Piet van der Graaf is Senior Vice President and Head of Quantitative Systems Pharmacology at Certara and Professor of Systems Pharmacology at Leiden University. From 2013-2016 he was the Director of Research of the Leiden Academic Centre for Drug Research. From 1999-2013 he held various leadership positions at Pfizer in Discovery Biology, Pharmacokinetics and Drug Metabolism and Clinical Pharmacology. He was the founding Editor-in-Chief of CPT: Pharmacometrics & Systems Pharmacology from 2012-2018 before becoming Editor-in-Chief of Clinical Pharmacology & Therapeutics. Piet received his doctorate training in clinical medicine with Nobel prize laureate Sir James Black at King’s College London. He has been awarded the 2024 Gary Neil Prize for Innovation in Drug Development from the American Society of Clinical Pharmacology and Therapeutics (ASCPT) and was the recipient of the 2021 Leadership Award from the International Society of Pharmacometrics (ISoP). Piet is an elected Fellow of the British Pharmacological Society and has published >200 articles in the area of quantitative pharmacology and drug development.
With 25 years of experience in computational biology. Andrzej has published models and software for analysis of molecular network dynamics and constraint based modelling of genome scale metabolic networks. Currently, his scientific work focuses on immuno-oncology and immunogenicity. He is a visiting Professor of Systems Biology at Surrey.
In addition to 18 years of mechanism-based QSP modeling in Neurology and Psychiatry as co-founder of In Silico Biosciences, Hugo has 20 years of experience in drug discovery and development as a Research Fellow at the Janssen Research Foundation laboratoria in Beerse, Belgium. At Certara, he leads a new Certara QSP consortium focused on neurodegenerative diseases.
Piet van der Graaf is Senior Vice President and Head of Quantitative Systems Pharmacology at Certara and Professor of Systems Pharmacology at Leiden University. From 2013-2016 he was the Director of Research of the Leiden Academic Centre for Drug Research. From 1999-2013 he held various leadership positions at Pfizer in Discovery Biology, Pharmacokinetics and Drug Metabolism and Clinical Pharmacology. He was the founding Editor-in-Chief of CPT: Pharmacometrics & Systems Pharmacology from 2012-2018 before becoming Editor-in-Chief of Clinical Pharmacology & Therapeutics. Piet received his doctorate training in clinical medicine with Nobel prize laureate Sir James Black at King’s College London. He has been awarded the 2024 Gary Neil Prize for Innovation in Drug Development from the American Society of Clinical Pharmacology and Therapeutics (ASCPT) and was the recipient of the 2021 Leadership Award from the International Society of Pharmacometrics (ISoP). Piet is an elected Fellow of the British Pharmacological Society and has published >200 articles in the area of quantitative pharmacology and drug development.
With 25 years of experience in computational biology. Andrzej has published models and software for analysis of molecular network dynamics and constraint based modelling of genome scale metabolic networks. Currently, his scientific work focuses on immuno-oncology and immunogenicity. He is a visiting Professor of Systems Biology at Surrey.
In addition to 18 years of mechanism-based QSP modeling in Neurology and Psychiatry as co-founder of In Silico Biosciences, Hugo has 20 years of experience in drug discovery and development as a Research Fellow at the Janssen Research Foundation laboratoria in Beerse, Belgium. At Certara, he leads a new Certara QSP consortium focused on neurodegenerative diseases.
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