Transforming gene expression signatures into IVD products for commercialization
SkylineDx is using its expertise to bridge the gap between novel gene expression signatures and commercially available diagnostic products with high clinical utility.
Bioinformatics combined with genomic technolo-gies, such as next-generation sequencing and micro-array techniques, is opening up new possibilities for diagnostic tests that could help in clinical decision making, such as more efficient patient stratification and prediction of patient’s response to therapies. SkylineDx is a commercial-stage company focused on the discovery, development and early commer-cialization of novel gene-signature-based diagnos-tics that works in collaboration with major academic centers of excellence.
“We specialize in bringing new gene expression signatures from the discovery phase through to early commercialization, and have developed an effective and thorough process to achieve this,” said Dharminder Chahal, CEO of SkylineDx (Fig. 1). “Our large team of researchers, bioinformaticians and business developers has evaluated over 200 ideas for gene signatures—we are researchers who really want to make a difference.”
Incorporated in 2013, with the aim of making per-sonalized medicine a reality, SkylineDx has developed early-stage assets in multiple myeloma into a com-mercial product, MMprofiler, and is building a port-folio of products in other disease areas. SkylineDx is headquartered in Rotterdam, the Netherlands, and has a commercial office in Laguna Hills, California, USA.
Discovery to commercialization
Over the past 18 months, SkylineDx has scouted over 200 gene signatures from respected universities and academic hospitals worldwide. Opportunities are analyzed in more detail following a well-defined screening process, which considers the clinical util-ity of the potential test, as well as the technology and investment needed to make it happen. Only a few dozen ideas make it through the screening phase.
The next step for potential gene signatures is a due diligence investigation, which involves exten-sive in-house bio-informatics data analysis to repro-duce the signature on the same dataset, as well as independent cohorts. “At this stage we also involve external scientists and key opinion leaders, who pro-vide valuable feedback on problems concerning the potential signature,” said Chahal. “If all goes well, we sign a license deal and take the signature into the development phase.”
Current product portfolio
SkylineDx developed the MMprofiler—a validated microarray-based prognostic test for risk assessment of patients with multiple myeloma, a type of bone marrow cancer. The test is based on SkylineDx’s proprietary SKY92 (or EMC92) gene signature—a prognostic signature of 92 genes for high-risk mul-tiple melanoma that was discovered by scientists at the Erasmus Medical Center in Rotterdam, the Netherlands1. Clinical studies have confirmed the prognostic value of SKY92 as a marker of high-risk disease in 16 independent cohorts.1-3
Within 1 year the MMprofiler was made available for research use only and in 2015 it was CE-IVD (in vitro diagnostic medical device) registered in Europe. In the US it will soon be available as a laboratory- developed test. Currently the test is in use globally in academic hospitals and in clinical trials.
Portfolio of gene signatures
SkylineDx is also developing new products in other disease areas, and has four gene signatures in the pipeline at different stages on the path to commer-cialization. Projects include a strategic collaboration with the Mayo Clinic, USA, to develop new diagnostic tests for patients with melanoma. Molecular testing could be performed on biopsy tissues collected at diagnosis, to help work out the likelihood that the melanoma has already spread to the lymph nodes, with the aim of preventing unnecessary SLN biopsy procedures in patients at a low risk of metastases.
The collaboration with the Mayo Clinic will optimize and further develop an algorithm to identify molecular risk factors associated with sentinel lymph node (SLN) metastasis, based on original research published by scientists at the Mayo Clinic4. Dermatologist Alexander Meves and his team discovered a set of gene expres-sion variables that could help identify patients with SLN metastases when used in combination with clini-copathological variables. The diagnostic test is now progressing from the discovery phase to validation.
SkylineDx projects start with discovery work and are further developed in collaboration with universities and pharmaceutical companies. The company is interested in early-stage gene expression biomark-ers that could be developed into diagnostic tests to improve clinical practice. Potential genetic biomark-ers could either have synergies with SkylineDx’s current pipeline or be a new franchise in a certain disease area.
“We have strong expertise in bioinformatics and a proven ability to transform gene expression sig-natures into commercial IVD products with high clinical utility,” said Chahal. “Our in-house team has the necessary skills for taking assets from early-stage discovery through to developing, validating and early commercializing innovative diagnostic tests.” SkylineDx is looking to set up collaborations with partners that can further commercialize its diagnostic products in geographical locations such as the US or Asia.
1. Kuiper, R. et al. Leukemia 26, 2406–2413 (2012).
2. Kuiper, R. et al. Blood 126, 1996–2004 (2015).
3. van Beers, E. H. et al. Clin. Lymphoma Myeloma Leuk. 17, 555–562 (2017).
4. Meves, A. et al. J. Clin. Oncol. 33, 2509–2515 (2015).
EVP Global Business Development
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Tel: + 31 (0)10 7044857