BARD1 Biomarker Technology

The proprietary BARD1 technology is a biomarker platform covering various BARD1 tumour markers, diagnostic and therapeutic methods and uses in multiple cancers. BARD1 tumour markers have potential utility as diagnostic biomarkers for the detection and monitoring of cancer and therapeutic targets for immunotherapies used in the treatment of cancer. The technology has potential applications across breast, ovarian, lung, colorectal and other cancers.

BARD1 is a protein that normally partners with the better known protein BRCA1 to act in repair of damaged DNA that otherwise could lead to the cell becoming cancerous. A range of deletions in the BARD1 protein leads to the loss of the ability of BARD1 to bind to BRCA1 and subsequently the loss of the cell’s DNA-repair mechanism. This increase in the level of the altered BARD1 proteins (BARD1 isoforms) ultimately can promote the formation and maintenance of tumour growth. The overexpressed altered isoforms of BARD1 can induce an immune response and the generation of antibodies. These “autoantibodies” appear in the early stages of many types of cancer. The autoantibodies bind to small defined sections (epitopes) on the altered BARD1 isoforms. Using panels of up to thirty small peptides (10 – 20 amino acids in length that have been synthesised in the laboratory) that represent the epitopes to which these autoantibodies bind, assays can be designed to detect the presence of autoantibodies to tumour-associated BARD1 in a patient’s serum. The probability of cancer being present is then determined based on an algorithm that integrates the level and abundance of different autoantibodies to altered BARD1 isoforms present in the patient’s serum compared to that of healthy people. The algorithm is developed from LASSO (least absolute shrinkage and selection operator) modelling of results of tests on several hundred cancer and control serum samples.

BARD1 Autoantibody Tests

The Company has three autoantibody tests in development for early detection of ovarian, breast and lung cancers. BARD1 autoantibody tests measure autoantibodies to variant BARD1 proteins in the blood and use a proprietary cancer-specific algorithm to combine these levels into a cancer score that identifies the presence or absence of a specific cancer.

BARD1 autoantibodies reflect the body’s early immune response to tumour formation and are present in the early stages of cancer, enabling the BARD1 tests to detect cancer earlier across all cancer stages before symptoms appear.

Multiple preclinical studies have been completed to evaluate BARD1 autoantibody panels and algorithms for detection of ovarian, breast and lung cancers. These preclinical, retrospective, case-control research studies in biobanked samples from cancer patients and healthy controls showed the accuracy of research BARD1 tests at discriminating people with and without cancer, and the potential of developing commercial BARD1 tests with high sensitivity and specificity for early detection of ovarian, breast and lung cancers. The table below provides a summary of the BARD1 autoantibody (AAb) test results for ovarian, breast and lung cancers.

Product Study n (cancer:normal) Training AUC Test AUC Sensitivity Specificity
OC-CA125 (ave-risk) 400 (200:200) 0.98 0.95 88% 93%
OC-R001 (high-risk)  261 (127:134) 0.99 0.97 89% 97%
BC-001a (ave-risk) 123 (1:64) 0.94 0.86 70% 88%
BC-001b (benign) 110 (61:49)   0.84 85% 76%
LC-POC (ave-risk) 187 (94:93) 0.96 0.86 80% 77%
LC-600 628 (395:233) 0.85 0.80 80% 68%

AUC is the accuracy of the test; Sensitivity is the % of people with cancer that correctly test negative.

BARD1 autoantibody test results

BARD1’s lead pipeline product is the BARD1-Ovarian test in development for early detection of ovarian cancer. BARD1-Ovarian has shown excellent results in early studies with diagnostic accuracy of 0.95 AUC, 88% sensitivity and 93% specificity for detection of ovarian cancer in average-risk women (OC-125 Study) and even higher diagnostic accuracy of 0.97 AUC, 89% sensitivity and 97% specificity in high-risk women with a family history of breast/ovarian cancer or carrying BRCA1/2 mutations (OC-R001 Study). BARD1-Ovarian has the potential to become an alternative ovarian cancer screening test in high-risk asymptomatic women with Hereditary Breast and Ovarian Cancer (HBOC) syndrome. It could also have utility as a follow up test when medical imaging results are unclear in symptomatic women or as an elective screening test in average-risk asymptomatic women.

BARD1’s second and highly complementary product is the BARD1-Breast test in development for early detection of breast cancer. BARD1-Breast has shown diagnostic accuracy of 0.86 AUC, 70% sensitivity and 88% specificity for detection of breast cancer in average-risk women (BC-001a Study) and could accurately distinguish malignant breast cancer from benign lesions with accuracy of 0.84 AUC, 85% sensitivity and 76% specificity (BC-001b Study). BARD1-Breast has the potential to be an alternative breast cancer screening test in average-risk asymptomatic women of all ages including women with dense breast tissue.

The Company’s third program is the BARD1-Lung test in development for early detection of lung cancer. BARD1-Lung has shown up to 0.86 AUC, 80% sensitivity and 77% specificity for detection of lung cancer in a proof-of-concept study performed at the University of Geneva.