Agendia NV, a Dutch SME, was founded in 2003 as spin-off from the Netherlands Cancer Institute. They pursue the commercialization of molecular diagnostics using DNA microarray technology for cancer. Agendia aims to be one of the key market players in genomic breast cancer profiling. One of the products Agendia is developing is MammaPrint, a breast cancer recurrence test. This test identifies the risk of recurrence of cancer after surgical treatment, so that the appropriate adjuvant treatment can be selected personalized on the patients tumor characteristics. Breast cancer is the most commom cancer in the world and the principle cause of death of cancer among women worldwide. Currently guidelines recommend that adjuvant therapy is to be considered for all patients with early invasive breast cancer after surgery. However this 'one size fits all approach' leads to a proportion of patients being over- or under treated as the risk of recurrence is difficult to determine. The advancements in molecular diagnostics are starting to improve the prognosis and treatment of breast- and other cancers. MammaPrint is a molecular diagnostic based on analyzing the entire human genome. Agendia’s solution therefore enables better clinical decisions, reducing over- and under-treatment and therefore leading to better health outcomes and less costs. MammaPrint can be used for all early stage breast cancer patients, which is unique in the field of breast cancer recurrence tests. As MammaPrint will be developed for more accurately identifying which breast cancer patients will gain the most benefit of adjuvant chemotherapy, the potential market for introducing MammaPrint is worldwide. In order to reach this full scale adoption, this project is focused to achieve the last clinical evidence for the clinical utility of this test needed for the uptake in EU and US clinical guidelines and reimbursement arrangements. This uptake is necessary for adoption of MammaPrint by physicians worldwide.

Colorectal cancer (CRC) is increasingly being recognized as a heterogeneous disease with distinct molecular subtypes. These subtypes have different biological processes at the basis of their disease and consequently their prognosis and responses to therapy are also different. We have previously developed molecular diagnostic assays using a single platform on routine FFPE tumour biopsies. These assays identify gene expression profiles with distinct prognosis and drug response phenotypes (CMS4/c-type, BRAF mutant-like, and MSI-like). Our overall objective is to develop targeted therapies more effective than the current therapies that do not take advantage of molecular classification of the disease to select patients for therapy. We therefore propose to perform 3 two-stage single arm multi-centre open-label phase II studies based on solid preclinical evidence and a sound scientific rationale for these subgroups of CRC patients: 1) combination of chemotherapy and a TGF-βR inhibitor (LY2157299) in patients presenting a C-type signature; 2) vinorelbine in patients with a BRAFm-like signature; and 3) an immunotherapeutic anti-PD-L1 drug (MPDL3280A) in combination with bevacizumab in patients with a MSI-like signature. The primary objectives of these studies are to determine the clinical efficacy (progression-free survival as primary endpoint), safety and tolerability of the experimental treatments in these molecularly selected populations. Mutation analysis at the beginning of treatment and monitoring by liquid biopsies might reveal further biomarkers that predict response in retrospective analysis. The project outcomes may have a significant impact in CRC patients with poor-risk prognosis worldwide as 40-50% of them present gene expression profiles matching one of the 3 approaches. Around 40,000 European CRC patients may potentially benefit from the results. Also, these may be translated to other cancer types with equivalent gene expression patterns/deregulated signalling pathways.