Targeted complete next-generation sequencing for companion diagnostics and personalized treatment of cancer

Project Information

SEQURE

Grant agreement ID: 806446

DOI

10.3030/806446

Project closed

EC signature date 18 April 2018

Start date 1 May 2018

End date 30 April 2020

Funded under

• INDUSTRIAL LEADERSHIP - Leadership in enabling and industrial technologies – Biotechnology

Total cost

€ 1 851 000,00

EU contribution

€ 1 295 700,00

Coordinated by

CERGENTIS BV
Netherlands

Periodic Reporting for period 2 - SEQURE (Targeted complete next-generation sequencing for companion diagnostics and personalized treatment of cancer)

Reporting period: 2019-05-01 to 2020-04-30

Summary of the context and overall objectives of the project

Cancer is the most common genetic disease and is a very difficult disease to treat effectively.

Cancer treatment is often:
• Unnecessary
For many cancer types and patients, a surgical operation will often be sufficient to remove all tumour cells in the patient’s body. However, the complete removal of tumour cells can currently not be reliably established and many patients are therefore, as a precaution, given additional (adjuvant) treatment.
• Ineffective
Cancer drugs only work on a subset of patients.
• Detrimental to the quality of life of the treated patient
Many cancer drugs result in severe side-effects and loss of quality of life.

The development of next generation sequencing (NGS) technologies and increasing understanding of the genetic complexity and heterogeneity of cancer has spearheaded the development of precision or personalized medicine.
However, current tests rely on the sequencing of short fragments covering only a fraction of the complete sequence of genes of interest. By missing clinically relevant genetic variants, including structural changes such as gene fusions, genetic diagnostics for personalized medicine is suboptimal and ineffective. In addition, the complete sequencing of genes enables the identification of tumour specific breakpoint sequences that are the ideal basis of personalised minimal residual disease (MRD) and circulating tumour DNA (ctDNA) tests to quickly and robustly monitor response to therapy. There is therefore an unmet need for a cost-effective technology, providing the complete sequence information and enabling detection of all genetic variants relevant for therapeutic decisions.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Dutch biotechnology company Cergentis has developed the proprietary TLA (Targeted Locus Amplification) sequencing technology platform, enabling targeted NGS sequencing of complete genes, across all gene regions (exons and introns) and all types of genetic variants (including structural changes) in a single rapid analytical procedure.

Within the SEQURE project Cergentis finalized the platform development for the analysis of tumour biopsies and validated customizable companion diagnostic kits, that will be offered to pharmaceutical companies to improve effectiveness of drug development in oncology clinical trials as well as to clinical partners to improve their cancer diagnostics. The project resulted in a fundamental improvement in the diagnostic value of genetic tests and therefore positions Cergentis’ technology for co-licensing agreements with global diagnostic & pharmaceutical companies to ensure effective large-scale clinical implementation of the TLA-based in-vitro companion diagnostic kits.

In short the project results can be summarized as follows:

Work-package 1 (TLA protocol development for tumour tissue FFPE sections) has been successfully executed and has resulted in a TLA protocol for FFPE material.

Work-package 2 (Validation of SEQURE test for MRD monitoring tool development) was also completed successfully. First clinical partners are routinely applying TLA for MRD monitoring test development in the support of the treatment of paediatric leukaemia patients and
multiple partners have initiated tests for personalised MRD monitoring for solid tumours.

Work-package 3 (Analytical validation of SEQURE test) has been successfully executed. Most extensive validation has been done with multiple leading diagnostic labs & research centres for lymphoma diagnostics. The project has confirmed the added value of TLA based sequencing of diagnostically relevant genes.

Work-package 4 (Bioinformatics tools/software development and automation of the protocol)) has been executed successfully and has resulted in a bioinformatics software package and a data representation software package that has been launched for end users.

Work-package 5 (Regulatory affairs/Quality system assurance) regulatory advice has been obtained for the execution of the entire work-package.

Work-package 6 (Commercialization and business development) Leading cancer research institutes, diagnostic labs, pharmaceutical companies and diagnostic companies have been approached and this has resulted in a significant number of important collaborations both for the clinical validation of SEQURE tests as well as the further co-development and future co-marketing/licensing of SEQURE tests.

Cergentis has presented at a number of conferences and continues to manage its granted patents and patent applications and assess third party IP. Cergentis continues to be confident that it will have a very strong IP position for SEQURE tests and be in the position to market its technologies & products via licensing agreements.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

SEQURE tests will fundamentally improve the quality of cancer genetics research and cancer genetic diagnostics by both improving the quality of cancer companion diagnostic tests (that are the basis for initial treatment decisions) and, by enabling ctDNA/MRD tests, fundamentally improving the speed and quality with which the efficacy of a given treatment can be assessed. Improving the diagnosis and treatment of oncologic patients addresses a significant health care and societal challenge. The current diagnostic solution will have multiple long-term social impacts. Above all, improved diagnosis and subsequent treatment will benefit patients’ well-being, quality of life and reduce direct (medical costs) and indirect (loss of productivity of the patient) expenses associated with morbidity and mortality of oncologic patients.

Cover of application note

Cover of application note