Report
Teaser, summary, work performed and final results
Periodic Reporting for period 1 - SEQURE (Targeted complete next-generation sequencing for companion diagnostics and personalized treatment of cancer)
Teaser
Next-generation sequencing (NGS)-based genetic tests are at the forefront of the adoption of personalized medicine in cancer. However, current tests rely on the sequencing of short fragments covering only a fraction of the complete sequence of genes of interest. By missing...
Summary
Next-generation sequencing (NGS)-based genetic tests are at the forefront of the adoption of personalized medicine in cancer. 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. 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. Cergentis seeks to finalize the platform development for the analysis of tumour biopsies and validate customizable companion diagnostic kits, that will be offered to pharmaceutical companies to improve effectiveness of drug development in oncology clinical trials. Company will perform validation of dedicated in-vitro companion diagnostic kits, markedly improving diagnosis and personalized treatment of cancer. Cergentis will integrate its proprietary TLA Technology with the DNA enrichment technologies that are currently the basis of standard next generation sequencing tests. The project will result in a fundamental improvement in the diagnostic value of such tests and therefore position 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. The SEQURE project will accelerate the commercialization of a unique diagnostic technology answering an unmet need in the personalized treatment of oncologic disorders.
Work performed
Work-package 1 (TLA protocol development for tumour tissue FFPE sections) is proceeding very well and has resulted in the successful development of a first TLA protocol for FFPE material.
Work-package 2 (Validation of SEQURE test for MRD monitoring tool development) is also proceeding well. First clinical partners are routinely applying TLA for MRD monitoring test development in the support of the treatment of paediatric leukaemia patients and the Princes Maximá Centre (the central Dutch paediatric cancer institute) is performing a large study to validate MRD tests developed on the basis of TLA analyses performed by Cergentis. The university of Turin is validating TLA based MRD tests in lymphoma.
Work-package 3 (Analytical validation of BRCA SEQURE test) is proceeding according to plan. A multiplex TLA primer set for the sequencing of the BRCA1 & BRCA2 genes has been successfully developed.
Work-package 4 (Bioinformatics tools/software development and automation of the protocol)) is proceeding well but has been hampered somewhat by a severe illness of one of Cergentis’ key bioinformaticians.
Work-package 5 (Regulatory affairs/Quality system assurance) is proceeding according to plan and regulatory advice is being obtained for the execution of the entire work-package.
Work-package 6 (Commercialization and business development) is proceeding well. Leading cancer research institutes, diagnostic labs, pharmaceutical companies and diagnostic companies have been approached and visited 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.
Final results
The expected results and impact of the project have not changed and are still as described in the SEQURE project proposal.
In brief: Successful development of 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.
Cergentis is already supporting MRD test development for paediatric leukaemia patients.