Biomarker Pipeline
Orion and its scientific founders have developed MethylScope® and MethylScreen® technologies, two powerful DNA methylation-based platforms, which scan the entire human genome to discover and validate novel cancer biomarkers. During the past three years, we have conducted more than 450 genome-wide, microarray-based experiments involving 6 common cancer types. This work has resulted in the discovery of 150 novel cancer biomarkers, which have been validated in collaboration with the Mayo Clinic and the University of Glasgow. Our rigorous process validates biomarkers using our growing specimen bank covering the 14 most common cancers. The bank contains more than 950 tumor, normal, and blood specimens (combined) from more than 800 patients.
Our next generation of cancer diagnostic products will emerge from this healthy pipeline of novel test leads.
Discovery Results
Using MethylScope, Orion's patented biomarker discovery platform technology, Orion scientists have built genome-wide high resolution DNA methylation maps of tumors and adjacent normal tissues obtained from more than 50 patients. The figure below shows a color-map of MethylScope measurements of candidate biomarkers that stratify tumor from normal tissue in breast, lung, and ovarian cancer. In each map, individual biomarkers are organized in rows and individual patient samples are arranged in columns. Methylation scores for each biomarker are represented from low methylation to high methylation by a color gradient from green to red.
Lead Biomarkers
The three panels below show the biological validation results of three leading biomarkers from our breast, lung, and ovarian cancer programs. Each dot in a panel represents the MethylScreen assay results for one patient sample. The MethylScreen assay's relative methylation score is on the y-axis, and patient samples by tissue type (tumor or normal) is shown on the x-axis. Our lead breast cancer biomarker was tested in a tissue panel with 205 patient samples, and has a sensitivity of 90% (correctly identifying 92/102 tumor samples) and a specificity of 96% (correctly identifying 99 of 103 normal samples). Our lead lung cancer biomarker was tested in a tissue panel with 50 patient samples, and has a sensitivity of 86% (correctly identifying 24/28 tumor samples) and a specificity of 100% (correctly identifying 22 of 22 normal samples). Our lead ovarian cancer biomarker was tested in a tissue panel with 52 patient samples, and has a sensitivity of 100% (correctly identifying 25 of 25 tumor samples) and a specificity of 100% (correctly identifying 27 of 27 normal samples). Orion's biomarkers are the most powerful epigenetic biomarkers discovered to date. For our lead diagnostic targets, we are currently evaluating the impact of differential methylation on cellular RNA and protein levels.
Tumor Types Carrying our Markers
Orion scientists evaluated the role each of the novel 150 biomarkers plays in 14 different human cancer types. In collaboration with the Mayo Clinic, the biomarkers were run against a large collection of patient samples, including tumor and normal samples from cancers of the breast, lung, ovary, bladder, cervix, colon, endometrium, esophagus, head and neck, liver, skin (melanoma), prostate, kidney, and thyroid. The control panel comprised whole blood samples from cancer-free individuals.
The figure above depicts the results of our cross tumor biomarker screen. MethylScreen assays measuring 150 biomarkers (organized in rows) were run against cohorts of tumor and normal specimens from each of 14 tissue types (shown in columns). Assays that stratified tumor from normal specimen in a cohort with a sensitivity >80% and a specificity >80% were considered hits (shown in black).