FAQ

Company Background

What does BARD1 Life Sciences Ltd (ASX:BD1) do?

BARD1 Life Sciences Ltd (BARD1 LSL) is an Australian biotechnology company focused on developing and commercialising non-invasive diagnostic tests for early detection of cancer. Its lead product, the BARD1 Lung Cancer Test, is a blood test in development for early detection of lung cancer, utilising novel tumour markers and a proprietary algorithm. The company’s pipeline also includes the BARD1 Ovarian Cancer Test in development for early detection of ovarian cancer, and high-value diagnostic and therapeutic projects at research-stage for multiple cancers. BARD1 is committed to transforming the early detection and prevention of cancer to help improve patients’ lives.

When was the company founded?

BARD1 Life Sciences Ltd was listed on the Australian Stock Exchange (as ASX:BD1) on 20/6/16 after acquiring BARD1AG SA.  BARD1 LSL is headquartered in Perth, Australia and has contract research laboratories at the University of Geneva, Switzerland.

How does the company plan to commercialise its technology?

BARD1 LSL plans to develop a portfolio of non-invasive diagnostic tests for early detection, diagnosis or monitoring of cancer. The company’s business strategy is to complete validation studies to demonstrate the performance of its diagnostic tests for detection of cancer and gain marketing clearance of its diagnostic tests in key marketplaces including the USA, Europe, Australia, and elsewhere. Subject to the results of these validation studies, the company will then seek to commercialise its diagnostic products through licensing the laboratory tests to clinical laboratory or major diagnostic partners for upfront fees, milestones payments, and royalties on sales. Importantly, BARD1 LSL will strive to create value for ASX:BD1 shareholders.

What are the market opportunities?

The global cancer diagnostics market was valued at US$100.9B in 2013, and is expected to reach US $168.6 billion by 2020, growing at a compound annual growth rate (CAGR) of 7.6%.1 The largest segment by application was lung cancer at US$26.0B followed by breast cancer at $20.1B, then colorectal, prostate, liver, and ovarian cancer at US$7.2B. There is a clear unmet clinical need for non-invasive, accurate and affordable diagnostic tests for early detection of cancer.

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Additionally, the global cancer vaccine market was valued at US$3.5B in 2016.2 BARD1 therapeutics have the potential to provide safe, effective and targeted solutions for the prevention and/or treatment of multiple cancers.

What's next for the company?

BARD1 LSL’s vision is to be a leader in the early detection of cancer to help save patients’ lives. The company’s research and development (R&D) activities are primarily focused on further developing and validating its lead product, the BARD1 Lung Cancer Test in 2017, with plans to enter a validation study for early detection of lung cancer in high-risk individuals who have undergone computed tomography (CT) scans. The study will be designed to demonstrate the superior sensitivity and specificity of the BARD1

1 Transparency Market Research (2014, Oct 31). Cancer Diagnostics Market: Global Industry Analysis, Size, Share, Growth, Trends, Forecast, 2014 – 2020. Available http://www.transparencymarketresearch.com/cancer-diagnostics-market.html, accessed October 15, 2016. 2 Dewan, S. (2016, Nov). Cancer Vaccines: Technologies and Global Markets. BCC Research. Available from http://www.bccresearch.com/market-research/pharmaceuticals/cancer-vaccines-technologies-markets-report-phm173b.html. Accessed March 15, 2017.

Lung Cancer Test compared to gold standard low-dose CT scanning to support future marketing and licensing. BARD1 LSL also plans to accelerate development of its second product, the BARD1 Ovarian Cancer Test, for early detection of ovarian cancer, and in 2018 to expand its diagnostic pipeline to develop new diagnostics tests for multiple cancers and intended uses. To support these programs the company intends to expand its management team and appoint an advisory board when appropriate. Additionally, the company plans to investigate therapeutic opportunities for its BARD1 Technology, initially through a small research collaboration to evaluate novel cancer immunotherapy formulations for use in the prevention and/or treatment of cancer in animal models, then if successful it will expand its therapeutic program and collaborations with the goal of early licensing to pharma partners.

BARD1 LSL aims to achieve the following value-adding milestones and strong news flow over the next 12-18 months including:

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What are your peer valuations?

There are several emerging niche diagnostic companies that are developing and commercialising diagnostic tests based on tumour markers for detection of cancer. Companies that have successfully validated and commercialised their diagnostic tests include Vermillion Inc and Oncimmune Ltd, that both have market capitalisations of around A$100M.

Vermillion Inc (NASDAQ:VRML) is a US-based diagnostics company that has commercialised 2 FDAcleared and CE marked diagnostics tests for risk assessment of ovarian cancer, and has a pipeline of gynaecological tests in development. VRML had a market capitalisation of A$150M (=USD115M) as at 15/3/17.

Oncimmune Ltd (LON:ONC) is a UK-based diagnostics company that has commercialised a CLIA-cleared and CE marked blood test to aid in the early detection of lung cancer, and has a development pipeline for liver and ovarian cancer. ONC had a market capitalisation of A$90M (=GBP57M) as at 15/3/17.

BARD1 Life Sciences Ltd (ASX:BD1) is an early-stage Australian-based diagnostics company with a proprietary biomarker technology platform, 2 diagnostic tests in development for early detection of lung and ovarian cancers, and several high-value diagnostic and therapeutic projects at research-stage for multiple cancers. BD1 had a market capitalisation of A$17M as at 15/3/17. BARD1 has achieved excellent preliminary results in proof of concept (POC) studies to date, and subject to continued positive results has significant upside potential as it progresses its fast-to-market diagnostic tests through validation towards commercialisation.

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BARD1 Technology

What is the BARD1 molecule?

BARD1 is both a gene and a protein that plays an important role in the normal cell cycle and tumour suppression. However, cancer cells express numerous abnormal BARD1 proteins that drive oncogenesis (cancer formation), and are correlated with cancer progression and poor prognosis.

Abnormal BARD1 proteins are immunogenic and induce circulating BARD1 autoantibodies in the blood. These abnormal BARD1 proteins (tumour-associated antigens) and autoantibodies are tumour markers that can be found in the blood of people with various cancer types and stages from early to late.

What is the BARD1 Technology?

The proprietary BARD1 Technology includes BARD1 tumour markers, diagnostic assays and algorithms. BARD1 tumour markers have potential utility as 1) diagnostic biomarkers for the detection and monitoring of cancer, and 2) therapeutic targets for immunotherapies used in the prevention or treatment of cancer. The BARD1 Technology has potential applications across multiple cancers including lung, breast, ovarian, prostate, and colorectal cancer.

Who are the inventors of the BARD1 Technology?

The BARD1 Technology is based on the discoveries of a leading scientific team at the University of Geneva, Switzerland (UNIGE) and University Hospital of Geneva (HUG). This scientific team, led by internationally renowned scientist Dr Irmgard Irminger-Finger, cloned the BARD1 gene and determined its biological function, pioneered translational research validating BARD1 autoantibodies as important biomarkers for cancer, built a solid intellectual property portfolio, established collaborations worldwide, received multiple grants and raised capital to fund the translation of the BARD1 technology for diagnostic and therapeutic uses in cancer.

Is the BARD1 Technology protected?

Yes. BARD1 LSL has established a strong intellectual property portfolio covering various BARD1 DNA and protein sequences, methods of diagnosis and treatment, and use in multiple cancers. The patent portfolio comprises 5 patent families with multiple granted and pending patents across key marketplaces including the US, Europe, Japan and other countries. In addition, the algorithm is protected by trade secret.

BARD1 Pipeline

What are BARD1 Tests?

BARD1 Tests are blood-based diagnostic tests for early detection of cancer. BARD1 Tests measure multiple BARD1 autoantibodies in the blood and use a proprietary diagnostic algorithm to combine these levels into a cancer score that identifies the presence or absence of a specific cancer.

What BARD1 diagnostic products are in development?

BARD1 Tests are currently in development for detection of lung cancer and ovarian cancers:

BARD1 Lung Cancer Test: ELISA-based blood test in development for screening and diagnosis of lung cancer. Preliminary results indicate that the BARD1 Lung Cancer Test has an accuracy over 93%, sensitivity greater than 90%, and false positives less than 10% for lung cancer.

BARD1 Ovarian Cancer Test: ELISA-based blood test in development for detection and monitoring of ovarian cancer. Preliminary results indicate that the BARD1 Ovarian Cancer Test has an accuracy of over 86% for distinguishing people with or without ovarian cancer.

The result of the BARD1 Test may help guide next steps. A positive test result may suggest that a patient should be referred for more invasive and costly imaging, biopsy or surgical procedures, whereas a negative test result may suggest that a high-risk patient should have an annual BARD1 Test to monitor changes in their test result.

What are the potential benefits of BARD1 Tests?

BARD1 Tests may address unmet needs for early detection of cancer in high-risk asymptomatic people to help inform decision-making and save people’s lives. Potential benefits include:

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Why is early detection of cancer important?

Early detection of cancer saves lives. Early detection testing is used to screen an asymptomatic target population at high-risk of developing a specific cancer type, with the goal of detecting the cancer at an early stage before symptoms occur and when treatment can be most effective. Narrowing the target population to high-risk groups is important when the prevalence of the disease in the overall population is low to improve the predictive value of the test and reduce the cost-effectiveness of the screening program. Screening programs are critical for the early detection of cancer to save people’s lives by enabling earlier treatment, improving patient outcomes, increasing survival and reducing healthcare costs.

Currently, both lung and ovarian cancers are often diagnosed at a late-stage after symptoms have appeared, resulting in a poor prognosis and overall 5-year survival of 18% for lung cancer and 46% for ovarian cancer in the US. Detection at an early stage when cancer is local rather than at a late stage when cancer is found distant may increase 5-year survival from 4% to 55% for lung cancer, and 29% to 92% for ovarian cancer, a potential survival improvement of 13x and 3x respectively (see below).

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What is the current standard of care for cancer detection?

Clinical guidelines recommend the current standard of care (best clinical practice) for diagnostic procedures for various cancers based on a systematic review of evidence and an assessment of the benefits and harms of alternative care options. Screening tests for cancer must have a high sensitivity and appropriate specificity to detect those with cancer and exclude those without cancer. No blood tests are currently recommended as the standard of care for screening or early detection of lung cancer or ovarian cancer in asymptomatic people, since currently available tests lack the sensitivity and specificity required for use in screening.

For lung cancer, current clinical guidelines recommend annual screening with the ‘gold standard’ lowdose computed tomography (LDCT) in high-risk asymptomatic adults aged 55-74 years with a greater than 30 pack-year smoking history who either continue to smoke or have quit within the past 15 years. Randomised clinical studies (NLST) showed that LDCT reduced the relative risk of mortality by up to 20% compared with chest x-ray alone.

For ovarian cancer, clinical guidelines recommend against routine screening in asymptomatic women of average (or population) risk. Three large randomised trials on ovarian cancer screening (PLCO, UKCTOCS and a European trial) found no evidence that any single test or combination of pelvic examination (PE), transvaginal ultrasound (TVUS) or CA-125 blood levels was effective in reducing mortality from ovarian cancer.

What are the results of BARD1 Tests so far?

The BARD1 Lung Cancer Test was evaluated in a Lung Cancer POC Study across 200 samples to have a ROC-AUC = 0.93-0.96, demonstrating high accuracy of over 93%, with over 90% sensitivity and 90% specificity for detection of lung cancer (see Prospectus dated 7/4/16). A recent Assay Feasibility Study to evaluate the BARD1 Lung Cancer Test across 40 samples on a commercial RUO instrument platform, yielded a ROC-AUC = 0.93 verifying the reproducibility and accuracy of the test (see ASX announcement of 8/2/17). These results demonstrated that the research-grade BARD1 Lung Cancer Test had an accuracy of over 90% for correctly identifying people with or without lung cancer in small case-control studies. This means that over 90% of people with known lung cancer correctly tested positive, and less than 10% of people without lung cancer incorrectly tested positive.

A new BARD1 Ovarian Cancer Test was evaluated in an Ovarian Cancer POC Study of 116 samples to have a ROC-AUC = 0.86, indicating the feasibility of developing an accurate blood test for detection of ovarian cancer (see ASX announcement of 22/9/16). These results were verified in a second study across 88 samples that confirmed the ROC-AUC = 0.86, and demonstrated the reproducibility, good sensitivity and specificity of the research-grade assay (see ASX announcement of  31/1/17).

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BARD1 LSL recently conducted a lung cancer confirmation study across 530 samples, and an ovarian cancer optimisation study across 300 samples. These studies were conducted in larger sample sizes to evaluate the BARD1 Tests across different cancer types and stages to optimise the performance and determine the limits of the tests for detection of lung and ovarian cancers. BARD1 LSL expects to announce the results from these studies by end of March 2017.

Are further studies required to commercialise the BARD1 Tests?

Yes, additional studies will be required to further develop, optimise and validate the research-grade BARD1 Lung Cancer Test and BARD1 Ovarian Cancer Test to enable marketing and licensing as proven, accurate, and reliable laboratory tests that can be performed on commercial instrument platforms by clinical laboratories.

How do the results of BARD1 Tests compare to marketed diagnostic products?

Several blood tests are currently available based on single or multiple tumour markers that are marketed for the risk assessment or detection of various cancers. Regulatory and health authorities do not consider certain tumour marker or multi-marker tests that are in common use to have sufficient sensitivity or specificity to be used alone for the screening or early detection of cancer. This is because tumour markers can be elevated by benign conditions as well as cancer. This is true of both the single-marker PSA test that has been shown in multiple studies to have a sensitivity of less than 21% for prostate cancer, and the CA-125 test that has a sensitivity of less than 66% for early-stage ovarian cancer.

Examples of available multi-marker tests for lung and ovarian cancer include:

  • EarlyCDT®-Lung, developed by OncImmune Ltd, is a CLIA-cleared and CE marked 7-marker blood test to aid in the risk assessment and early detection of lung cancer. It has been validated to have a sensitivity of 40% and specificity of 90% for detecting lung cancer in high-risk patients and those with indeterminate nodules.
  • OVA1®, developed by Vermillion Inc, is a FDA-cleared and CE marked 5-marker blood test for risk assessment of ovarian cancer in women with pelvic masses. It has been validated to have a sensitivity of 92% and specificity of 54% for ovarian cancer risk assessment. A second-generation FDA-cleared and CE marked test called Overa is based on a modified 5-marker panel and validated to have an improved specificity of 69% for ovarian cancer risk assessment in women with pelvic masses.

How are diagnostic tests regulated?

Diagnostic tests are typically regulated as medical devices. BARD1 Tests will initially be developed as ‘inhouse’ laboratory tests requiring marketing clearance under CE mark in Europe, ARTG Listing in Australia, and as a CLIA-certified LDT in the US.

In February 2017, BARD1 LSL announced that it had completed an assay feasibility study. What did it achieve and what is the significance?

The Assay Feasibility Study was performed by Meso Scale Diagnostics (MSD) to evaluate the researchgrade BARD1 Lung Cancer Test on its research-use-only (RUO) instrument platform. MSD performed various studies to determine the best assay method for further development of the BARD1 Lung Cancer Test. The study achieved a receiver operating characteristic (ROC)-area under the curve (AUC) = 0.93, which was comparable to the ROC-AUC = 0.96 previously reported for the company’s Proof of Concept (POC) Study.

These results verified that the research assay was reproducible in an independent laboratory on a commercial RUO instrument platform, had high accuracy of 96% for detection of lung cancer, and could be further developed as a robust test for performance by clinical laboratories. This is an important step in the development of a research-grade assay towards a robust laboratory developed test for use in a clinical laboratory.

What is the Cancer vaccine project?

It is a research project to evaluate the effectiveness of novel BARD1 cancer vaccine formulations for use in the prevention and/or treatment of cancer in industry-accepted animal models. BARD1 LSL expects to update the market on this collaboration opportunity by end of Mar-17.

Diagnostic Test Terminology and Performance Measures

What is an in vitro diagnostic (IVD)?

In Vitro Diagnostic (IVD) tests are medical devices that are used in vitro for the examination of specimens (including blood, urine and tissue samples) taken from the human body to provide information on diseases, conditions, or infections, and are sold as diagnostic kits to laboratories, health professionals, or consumers for home use.

What is a laboratory developed test (LDT)?

Laboratory-Developed Tests (LDT) are “in-house” tests that are designed, manufactured and used in a single laboratory, and sold as a service to clinics, patients, and third-party payers.

What is an ELISA test?

Enzyme-Linked Immunosorbent Assay (ELISA) is a biochemical method used to detect the presence of an antibody or antigen in a liquid sample. ELISAs are the most widely used assay type, as it is a relatively fast and inexpensive test method.

What are tumour markers?

Tumour markers are substances that are produced by cancer or by other cells of the body in response to cancer, such as proteins, gene expression patterns and DNA fragments. Tumour markers are often found at higher than normal levels in the blood, urine, stool, tumour tissue, or other tissues or body fluids of some people with cancer. However, tumour markers may be elevated, normal or absent in people with cancer, can vary over time, and may be present at an early or later stage of cancer. Tumour markers can be used to aid the detection, diagnosis and management of cancer to help improve patient outcomes and survival.

What is a ROC curve?

A receiver operating characteristic (ROC) curve graphically shows the performance of a diagnostic test by plotting the true positive rate (TPR or sensitivity) for correctly detecting cancer in diseased patients against the false positive rate (FPR, or 1-specificity) for incorrectly identifying cancer in non-diseased (healthy) patients, at various threshold settings. A ROC curve can be used to compare diagnostic tests. A good diagnostic test must demonstrate a high sensitivity (correct diagnosis) and acceptable false positive rate (“cancer scares”) for the disease.

What is the AUC?

The area under the curve (AUC) interprets the accuracy of the test in distinguishing between patients with and without cancer, where the greater the AUC the better the test. A perfect test would have an AUC=1.0, an excellent test AUC=0.9-0.99, a good test AUC=0.8-0.89, and a useless test AUC=0.5. In a clinical context, an AUC=0.90 means the probably of correctly classifying a patient as being positive or negative for cancer is 90%.

What is sensitivity?

Sensitivity (or true positive rate) is the percentage of patients with cancer that were correctly identified with a positive test result. High sensitivity is important because it minimises the number of patients with cancer that are missed (false negatives). For example, if a test has a sensitivity of 90% for lung cancer, then it detects 90% of people with lung cancer and misses lung cancer in 10% of people with cancer.

What is specificity?

Specificity (or true negative rate) is the percentage of patients without cancer that were correctly identified with a negative test result. For example, if a test has a specificity of 90% for lung cancer, then 90% of healthy people will correctly test negative and the other 10% will be false positives.

What is a false positive?

False positive (1 – specificity) is the percentage of heathy people without cancer that were incorrectly identified with a positive test result. A diagnostic test with low specificity for cancer may have an unacceptably high false positive rate (“cancer scares”) that can lead to patient anxiety and over referral of healthy individuals for unnecessary invasive and costly follow-up procedures.

What is accuracy?

Accuracy is the percentage of true results. It is an overall measure of test reliability in correctly identifying people with and without cancer. It is calculated by dividing the number of true positive and true negative results by the test population.

What are predictive values?

Positive predictive value (PPV) is the probability that the disease is present when the test is positive in a given population with known disease prevalence.

Negative predictive value (NPV) is the probability that the disease is not present when the test is negative in a given population with known disease prevalence.

For example, in a high-risk population with 20 cases of disease for 1000 people (2% prevalence), a diagnostic test with a specificity of 90% and sensitivity of 90% would have a PPV=15.5% and NPV=99.7%.

Acronyms

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