Translational Science in drug development
21 June 2019
Article written by Cees Korstanje – Translational Science Director/Director Pharmacology
Many people who have just finished a PhD might be working on drug development. However, they often will not know all the connecting processes involved in bringing the drug into patients. These connecting processes are also referred to as Translation Science (TS). In this article, Cees Korstanje elaborates on what TS means and what goals it can serve.
TS is more a process and art of connecting cross-functional biological data than a defined science entity. TS in early drug development is a process of selection nonclinical tools and generation of data to build a biological concept and thereby generate confidence that the chosen drug and drug target will lead to a positive proof of concept in patients. In this process, the ‘translational science plan’ is the blueprint and defines what the critical hurdles are and what tools and models are required to generate the ‘confidence end points’. Execution of this plan requires a multidisciplinary interaction space where, dependent on complexity of issues, biological and pharmacological models, sample/readout collection schemes, sample type, bio-analytics platform, arithmetic models and data analysis matrices are compiled. Confidence end points are usually sets of biomarkers, and biomarkers are mostly bio-analyte levels that mark the status of a critical part of the disease process as influenced by the drug.
In current practice TS expertise input in clinical phases of drug development is not limited to defining and measuring a biomarker palette in patients to support selection of patients, individual dose selection, and clinical end points in registration trials, but can also be used for decision-making in a due diligence process, or to generate data for health-economic value purpose. This in particular for therapeutic regimens with combinations therapy in high-value markets, such as oncology. For a new therapeutic modality to find identity and to proof its therapeutical benefit in a complex therapeutical treatment schedule, it is pivotal to document what shifts in biomarker patterns are caused by the newcomer.
Obviously, a higher demand of more data in a regulated environment like pharma, urges to be critical on using a multitude of biological models, analytical platforms and data algorithms, since everything needs to meet quality standards and requires validation steps that may consume much time and resources. Therefore, combining drug target genomics, host-immune system avidity and systems biology knowledge with concentration-response and ligand-target characteristics may be a sound basis to explore deconvolution methodologies for obtaining the pivotal quantitative systems pharmacology (QSP) descriptors aiming at higher benefit with lower spend.
Advancements in analytical genetics and bioanalytical science have led to important reductions in sample volumes and sample work-up procedures to bring multiplex technology into analytical platforms. Liquid biopsy in combination with personalized ctDNA assays is a compact and practical tool in clinical oncology research and patient care. Reliable quantitative histology slide platforms have become available for wide applicability. Sensitivity and precision improvements e.g. in metabolomics now make applications in QSP programs feasible.
So keen use of TS is helpful to design tailored biomarker programs with minimal accumulation of analytical platforms in QSP matrices in a cost-effective way to satisfy the needs to connect drug development phases from bench to bedside.
Cees Korstanje is an experienced Science Director in the pharmaceutical industry. He is skilled in: Pharmacology (in-vivo/vitro, model development, mode-of-action profiling, safety pharmacology, and PK/PD projects), Translational Science and Biomarkers, and Clinical Pharmacology studies in the context of Drug Development programs in different therapeutical areas and >5 Marketing Authorizations, Lead in collaborations with academic and CRO partners (a.o. in Horizon2020 programs).
He graduated from Leiden University (Pharm D) and Amsterdam University (PhD), and worked at Utrecht University (Veterinary pharmacology) before entering the Pharma business, with 70+ scientific publications.
We would like to thank Cees Korstanje for sharing his knowledge on Translational Science within our Biotechnology Community. Need assistance in your projects? You can reach out for any and all consultancy questions via his website.
Are you currently working with TS and want to share your experience? Please send us an email to info@biotechnologycommunity.com.