Hadasit Bio-Holdings

BioMarCare Technologies

BIOMARECARE Colon-MarCarePlex™ Technology Offered for Investment/Strategic Partnering

BioMarCare Technologies, a leader in the development of plasma RNA biomarkers for colorectal cancer (CRC), is looking for a strategic partner or for an investor for the development of its proprietary Colon-MarCarePlex™ technology for the screening of pre-cancerous polyps and early cancer detection in blood.

Breakthrough Blood RNA Biomarkers Push Accurate CRC Screening Test Forward

Plasma circulating free RNAs is considered to be fragile and more susceptible to degradation. We were able to develop a breakthrough reproducible and low cost diagnostic procedure to purify and stabilize RNA extracted from plasma sufficiently intact to allow analysis by reverse transcription-PCR.

This technology was employed to depict the profile of colorectal tumors by combination of microarray technology analysis of circulating RNAs from patients with CRC with information available through bioinformatics analysis of literature. This enabled us to derive a reliable RNA profile of 8 biomarkers for pre-cancer diagnostic.

Discovery:

To identify gene profile that is indicative to advanced adenoma and early colorectal cancer versus expression levels in plasma of healthy individuals, a gene expression analysis using Affymetrix array was performed and revealed plasma expression of 6,577 genes that shared a common presence in plasma of all subjects. The bioinformatics search yielded 4 gene lists that were compared with the gene list reveled by the Affymetrix array. In order to minimize the number of predictive biomarkers and to obtain a limited number of best performing genes a qPCR method was employed on 72 common genes.  Each ofthe 72 common genes was tested on 20 plasma cfRNA samples collected from 3 clinical groups: CRC, Advanced Adenoma and Healthy individuals.

BioMarker selection:

This selection yielded 17 genes that were identified as differentially expressed between control and disease samples.In order to establish the final In-Vitro diagnostic profile each of the 17 genes were tested with 50-100 patients’ plasma RNA samples allowing downsizing the selected signature to 8 biomarkers. Carefully chosen marker combinations formed a solid base to become a sensitive screening assay.

Clinical study:

Patients were recruited prospectively from 3 clinical sites. Plasma was collected from 3 patient groups:

 i) Colonoscopy negative individuals;  

ii) Advanced adenomatous polyps (pre-cancer) – confirmed by colonoscopy; and

iii) Colorectal cancer patients (stages I-III)

The population for this clinical study was symptomatic recruited from gastroenterology units. A future prospective clinical validation will require recruitment of asymptomatic population in a screening setting.

Patent Protection:

A PCT application was filed in light of Supreme Court Prometheus-Mayo decisions and covers multi RNA biomarker panel combination for colorectal cancer screening

Colon-MarCarePlex™: Powerful Biomarker Panels Based on Solid and Proven Technology

Analysis of the experimental qPCR data revealed 8 biomarkers.

For pre-cancer predication, the patient’s cohort included 46 colonoscopy negative subjects and 38 patients with advanced adenoma polyps. The leading biomarker profile was based on combination model of two genes with the following performance characteristics: Receiving operating characteristic (ROC) curve analysis for the model yielded 70.5% AUC (95% Asymptotic CI: 58.5%-82.5%) with P value <0.001 for discriminating advanced adenoma polyps patients from healthy individuals. The specificity was above 85% and the maximum Youden index meet at a point 2 with performance sensitivity of 60% and specificity of 87%.

For colorectal cancer detection, the patient’s cohort included 41 colonoscopy negative subjects and 28   patients with CRC. Logistic regression was used to develop a classification model for Cancer & Healthy using  the 8 biomarkers with the following performance characteristics: ROC curve analysis for the model yielded 84.3% AUC (95% Asymptotic CI: 74.8%-93.9%) with P value <0.001. The specificity above 85% and the maximum Youden index meet at a point 0.84 with performance sensitivity of 75% and specificity of 93%.

These results document the achievability of molecular profiling of colorectal tumors by qPCR of RNAs circulating in plasma, notwithstanding the challenges posed by low and labile amount of the targets sample. 

A Meaningful Market with Room to Grow

Blood based tests have long been sought in the cancer screening for their convenience and potential for higher compliance. Nevertheless, on late 2014 a new screening molecular stool test for colorectal cancer named Cologuard achieved simultaneous approval from FDA and the Centers for Medicare & Medicaid Services.  This relatively complicated DNA & ELISA stool assay requires sample collection and shipment to a central service laboratory. Yet, this product opened the gate for the introduction of simple, In-Vitro molecular diagnostic detection kit based on cfRNA in blood using a routine qPCR format.    

Because patients at earlier stages of CRC are often asymptomatic, CRC screening allows for early identification of cancer at stages where treatment is more likely to be effective. Five-year survival rates for Stages I-II CRC cases are 94% and 82%, respectively. Colon-MarCarePlex assay is a non-inferiority assay for CRC sensitivity when compared to fecal test (FIT) and a superiority test for pre-cancer (advanced polys) sensitivity. Given that identification of pre-cancer is important for reduction of CRC incidence and that detection of CRC at early stages has the potential to significantly reduce mortality, an optimal new screening tool should have high sensitivity for CRC and also capable to identify pre-cancer in blood. Colon-MarCarePlex high sensitivity in plasma enables screening independently of tumor location and can be with great clinical utility due to patients’ compliance.

BioMarCare Technologies Ltd. is looking for an investor or strategic partner for the development of its Colon-MarCarePlex™ technology.

BioMarCare Technologies
http://www.biomarcare.com
Founded: 2009
HBL's Holdings: 66%