Simple blood test can detect lung cancer with high sensitivity and specificity - results from large clinical validation study published in the Journal of Clinical Oncology

-- GENSIGNIA plans to introduce minimally invasive diagnostic test which is urgently needed to improve the diagnostic performance of high resolution imaging for lung cancer detection

LONDON, MILAN, and SAN DIEGO, Jan. 13, 2014 /PRNewswire/ -- GENSIGNIA Ltd, a London-based, privately held molecular diagnostics company with laboratory operations in San Diego, CA, and Fondazione IRCCS, Istituto Nazionale dei Tumori (INT), Milan, a National Cancer Research Center in Italy, announced today that positive clinical validation results for the microRNA signature classifier (MSC) Lung Cancer assay were published in the Journal of Clinical Oncology (JCO). The results demonstrate for the first time that a blood-based test can significantly reduce the high false positive rate associated high resolution imaging, specifically with Low-Dose Computed Tomography (LDCT or Spiral CT), the current recommended lung cancer screening methodology for heavy smokers.  The MSC Lung Cancer assay had high sensitivity and detected lung cancer up to 2 years prior to diagnosis by LDCT. Aspects of the study results were presented on January 8^th in San Diego as a plenary talk at the AACR-IASLC Molecular Origins of Lung Cancer meeting by Gabriella Sozzi, Ph.D., Professor, Head of Cancer Genomics at INT. In 2014, GENSIGNIA intends to introduce a lung cancer diagnostic test initially in the U.S.

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Prospectively collected blood samples from 939 heavy smokers from the randomized lung cancer screening trial comparing LDCT versus observation (Multicentric Italian Lung Detection [MILD] trial; INT) were used to validate the diagnostic performance and demonstrate clinical utility of the MSC Lung Cancer assay, a 24 microRNA expression signature assay. Heavy smokers from the MILD trial that were cancer-free (n=870) or diagnosed with lung cancer (n=69) were examined in this correlative study. The MSC Lung Cancer assay demonstrated an overall sensitivity of 87% for the presence of lung cancer. For all subjects, the MSC Lung Cancer assay had negative predictive values (NPVs) of 99% and 99.86% for detection and death-by-disease (lung cancer), respectively, indicating the test's high specificity for correctly identifying subjects without lung cancer.  The high specificity of the MSC Lung Cancer assay resulted in a 5-fold reduction in the false positive rate of LDCT-identified suspicious lung nodules in heavy smokers that did not have lung cancer.

"The 5-fold reduction in false positives obtained by combining the MSC Lung Cancer assay to the results of the LDCT scan is of great clinical relevance in the context of reducing the false positive rate and the potential side effects associated with repeated LDCT scans or other unnecessary invasive diagnostic follow-ups." stated Dr. Ugo Pastorino, Head of Thoracic Surgery Unit, Chairman of Department of Surgery, Istituto Nazionale dei Tumori, Milan, Italy.

This correlative study in lung cancer is the first of its kind, clinically validating a biomarker using prospectively collected blood samples from a large randomized lung cancer screening trial. In addition to a significant reduction in the rate of false positive results, the performance of the MSC Lung Cancer assay was independent of the stage of lung cancer and time prior to detection of cancer with LDCT (up to two years prior). This suggests additional potential utility for diagnosis and early detection with the MSC Lung Cancer assay.

"We have developed a minimally invasive molecular diagnostic assay that quantifies the expression of specific miRNAs which are freely circulating in blood and indicate the presence of lung cancer." stated Gabriella Sozzi, Ph.D., Professor, Head of Cancer Genomics at INT. "Overall, the results of our study support the use of the assay as a tool to improve the early detection of lung cancer."

Globally, approximately 1.1 billion people smoke, and in the U.S, there are approximately 19 million heavy smokers, or those that smoke at least 1 pack per day. LDCT is a recommended method for screening lung cancer in high risk individuals, primarily heavy smokers. Published in June 2011 in New England Journal of Medicine, the landmark NCI-sponsored National Lung Screening Trial (NLST) reported a 20% relative reduction in mortality with LDCT screening of high risk individuals with a history of ≥30 pack-years and ≤15 years since they quit smoking, versus annual chest X-rays. In the NLST, 24.2% of subjects screened were deemed positive for lung cancer, and the majority of positive screens led to additional tests. When a positive screening result was found, 96.4% of the LDCT tests were deemed "false" positives. As a result, the cost of screening large numbers of high risk individuals, the potential harm associated with LDCT screening, and the high false positive rate with LDCT highlight the need for complementary biomarkers to improve diagnostic performance.

"Screening heavy smokers with Spiral CT scans saves many lives, but the cost-effectiveness of this approach has been questioned due to the high rate of false positives." stated Gabriele Cerrone, Founder and Executive Chairman of GENSIGNIA. "In combination with a Spiral CT, the MSC Lung Cancer assay significantly reduces the false positive rate, which can translate in substantial savings for the global healthcare system by avoiding the need for additional workups and scans required to confirm diagnosis."

About Lung Cancer

According to the World Cancer Research Fund International, lung cancer is the most common cancer in the world and it is estimated that smoking will kill up to a billion people worldwide this century. In the U.S., it is the second most common cancer, but according to the American Cancer Society, lung cancer is by far the leading cause of cancer-associated death. More people in the U.S. die of lung cancer than colon, breast, and prostate cancers combined. The symptoms of lung cancer typically do not appear until the disease is already in an advanced, non-curable stage. Even when the symptoms of lung cancer do appear, they are often mistaken for other problems such as an infection or the long-term effects from smoking, which often delays diagnosis. As a result, over 80% of lung cancer patients die within two years of diagnosis.

About miRNAs and the MSC Lung Cancer Assay

MicroRNAs (miRNAs) are small noncoding ribonucleic acids (RNAs) that modulate gene activity and are aberrantly expressed in cancer. They are tissue- and disease-specific molecules actively released by tumor cells and their microenvironment into the circulation packaged in exosomes or associated with ribonucleoprotein complexes to protect them from degradation. Due to their small size and stability, miRNAs can be measured in biological fluids such as plasma and serum and can serve as circulating biomarkers. Drs. Sozzi and Pastorino had reported the development and validation of plasma-based miRNA signatures from subjects in two independent LDCT screening studies, demonstrating that quantitative measurement by real-time RT-PCR of 24 circulating miRNAs is diagnostic and prognostic in lung cancer (Boeri et al., 2011). This biomarker assay is designed to offer the potential for early detection of lung cancer thereby avoiding the costs and complications associated with unnecessary tests following a false positive diagnosis using LDCT or chest X-rays.

About Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Fondazione IRCCS, Istituto Nazionale dei Tumori (INT), Milan, was founded in 1928 and has become a national center of excellence for academic research and cancer treatment, and has been awarded the qualification of Comprehensive Cancer Center by the Organisation of European Cancer Institutes (OECI). INT delivers outstanding patient care through technological avant-guard, groundbreaking research, and continuous personnel development.

About GENSIGNIA

GENSIGNIA Ltd is a London-based molecular diagnostics company with operations in San Diego, USA and Milan, Italy. GENSIGNIA focuses on the development and commercialization of novel molecular diagnostic blood tests designed to provide more accurate detection of cancers.  In 2014, GENSIGNIA intends to introduce a lung cancer diagnostic test initially in the U.S.

Statements in this press release about the Company's expectations, applications of its technology, markets, launch of tests and other statements that are not historical fact are "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and are based on management's current beliefs, assumptions, estimates and projections. Actual results could differ materially from those projected in the forward-looking statements for various reasons, including risks associated with product and test development, test transfer to contracting labs, government regulation, market acceptance, limited commercial experience and dependence on key personnel and financing.