Science Pool

Molecular Profiling – A Gamechanger for Personalised Medicine

Molecular profiling of cancer patients is a great success story: A single test can analyse a patient’s genome to identify genetic alterations from the four main classes that are known to drive cancer growth: base mutations, gene insertions and deletions, copy number alterations, and rearrangements or fusions. In addition to retrieving information on these common oncogenic drivers, it is also possible to obtain new information on complex or rare biomarkers from the same test. Based on this knowledge, oncologists can select the most suitable cancer therapy, often a combination of increasingly targeted drugs that address a specific cancer mechanism. As a result, molecular profiling approaches have been integrated to mainstream clinical oncology, and targeted therapies have become standard of care for patients known to express certain mutations in their tumours.

Molecular profiling – suitable for many indications

This success has fueled interest in the molecular profiling of other complex indications as well and has also expanded the profiling process: not only the sequence is analysed, but also methylation and expression patterns. The profiling toolbox also includes proteomics to analyse the proteins expressed in a cell or tissue and metabolomics to study the metabolism of diseased cells, tissue, organs, and patients.

The wealth of data generated by these approaches is now being analysed by artificial intelligence linking these data to individual patient information to identify biomarkers that provide insights into the genesis and course of the disease and that may help to stratify patients, predict outcome, and select therapies. The goal of these efforts is the development of precision medicines for complex diseases not only in cancer, but also in autoimmune or other chronic diseases – a clear departure from the old paradigm of “one-drug-fits-all.”

By systematically integrating data science across its discovery and development platform, Evotec aims to lead this paradigm change towards highly effective personalised medicine of the future. It has industrialised the generation of genomics, transcriptomics, proteomics and metabolomics data with its EVOpanOmics platform and has built a strong complementary data analytics platform driven by artificial intelligence and machine learning with EVOpanHunter. This platform makes use of molecular patient databases, bioinformatics and the data generated by EVOpanOmics.

Integrated approach

The company is in a unique position as these platforms are complemented by Evotec’s multimodality expertise spanning from small molecules and chemistry to biologicals, antisense molecules to cell and gene therapy. Moreover, with its iPSC platform Evotec’s scientists can design and test patient-derived disease models for comprehensive compound profiling in the treatment development process, focusing on disease relevance throughout the entire pre-clinical and clinical steps.

Already, Evotec has closed a number of collaborations in this field. In 2020, it joined forces with Indivumed GmbH for the discovery and development of first-in-class therapeutics for the treatment of non-small cell lung cancer (NSCLC). The collaboration combines Evotec’s bioinformatics, advanced analytics and AI capabilities as well as its small molecule and antibody discovery platforms, with the NSCLC cohort of Indivumed’s multi-omics cancer database “IndivuType.”

In the same year, Evotec closed a partnership with the University of Oxford, gaining access to biospecimens from the biobank Quality in Organ Donation (QUOD), an initiative of the university’s Nuffield Department of Surgical Sciences (NDS) in close collaboration with the National Health Service Blood and Transplant (NHSBT) organisation in the UK. QUOD is providing blood, urine and tissue samples from heart, lung, liver and kidney from consented organ donors for researchers with anonymised integrated medical records. Evotec at present is investigating first samples from 1,000 individuals using a comprehensive multi-omics approach (genomics, transcriptomics, proteomics, metabolomics) to complement its existing patient database. The goal is to enable a better understanding of disease mechanisms across indications, i.e. cardiovascular, kidney, and liver diseases.

A particular focus of Evotec is chronic kidney disease (CKD). CKD is an impending public healthcare challenge, and the traditional diagnostic biomarkers, e.g. creatinine, have low sensitivity and specificity. Therefore, novel diagnostic and prognostic biomarkers for patients at high risk of early-stage progression are urgently needed. They may not only provide information about the etiology and mechanisms underlying CKD progression, but may also enable early diagnosis and the selection of appropriate therapies, thereby personalising therapy. Evotec closed a strategic partnership with the University Hospital of Erlangen for the molecular analysis of biospecimens from the German Chronic Kidney Disease (GCKD) cohort study initiated by the university. GCKD is the world’s largest cohort study on chronic kidney disease, enabled by scientists from eleven universities and more than 150 practicing nephrologists that monitor more than 5,000 patients with CKD. The study comprises sampling of biospecimens, clinical data and multiple interviews. The collaboration aims to better understand the various kidney disease etiologies, their respective disease mechanisms, progression, and potential complications. Together with Evotec’s existing molecular patient database, this systematic integrated exploitation of the GCKD biobank is expected to provide novel starting points for drug discovery and the identification of biomarkers, enabling precision medicine approaches for highly effective treatment options for clearly defined patient populations.

Also in kidney disease, Evotec is collaborating with Novo Nordisk to jointly identify and develop novel targets based on comprehensive medical and molecular data sets of thousands of chronic kidney disease patients, and with Chinook Therapeutics to identify, characterise and validate novel mechanisms and discover and develop precision medicines.

All collaborations leverage the EVOpanOmics and EVOpanHunter platforms with the overarching goal to develop disease-modifying therapies for the targeted treatment of patients with unmet medical needs.