THE FACES OF ORAL CANCER ARE CHANGING K N OWING E A R L IE R TO GIV E THEM A L ATE R Introducing the First and Only Tests to Aid in the Diagnosis of Oral Cancer by Detecting a Tumor-Initiating and Stem Cell-Associated Biomarker The OncAlert Oral Cancer product line is comprised of proprietary tests that detect CD44 and total protein. These tests are optimized for easy use by collecting samples via an oral saline rinse. The test results, along with other clinical factors, can aid in the early detection of oral cancer (including oral and oropharyngeal cancer).
ORAL CANCER: A GLOBAL HEALTH ISSUE Oral cancer is a global challenge with more than 529,000 cases and nearly 292,000 deaths each year. 1 Worldwide 5-year survival rate is only 50% due to delayed intervention with more than half of diagnoses at stage III and IV. 2 Earlier detection (stage I and II) yields survival rates up to 80%-90%. 2 WHO IS AT RISK FOR ORAL CANCER? Oral cancer is common in both developed and developing countries. Prevalence is substantially higher among men Key risk factors are linked to preventable causes Tobacco use: smoking or smokeless Excessive alcohol use Infection with human papillomavirus (HPV) MORE THAN HALF OF ORAL CANCER IS DETECTED IN STAGE III AND IV OFTEN TOO LATE 2 2
ONCALERT : THE SCIENCE OF EARLIER THE FIRST AND ONLY TESTS TO IDENTIFY A TUMOR-INITIATING AND STEM CELL-ASSOCIATED BIOMARKER FOR ORAL CANCER The OncAlert Oral Cancer RAPID Test and OncAlert Oral Cancer LAB Test are technologically advanced and highly accurate methods to aid in the early detection of oral cancer through the unprecedented detection of CD44 and total protein levels collected in an oral rinse. CD44 is significantly overexpressed in oral cancer even in early stages. The qualitative biomarker assay (OncAlert RAPID), with a negative predictive value (NPV) of over 90%, performs well in ruling out oral / oropharyngeal cancer when a reasonable suspicion exists. ONCALERT: IMPROVING THE STANDARD OF CARE EXAMINATION TYPE SENSITIVITY SPECIFICITY Conventional 64 31-76 OncAlert RAPID 71-84* 30-50* OncAlert LAB 80** 93** * Sensitivity or Specificity is dependent upon selected biomarker threshold. * * Without clinical variables the OncAlert LAB Test will yield a false negative rate of 15% while the false positive rate is 52%. The biomarker assay performs well in confirming when there is a reasonable suspicion of cancer, but will not effectively assist in the discrimination of more benign processes. OncAlert LAB, a quantitative algorithm which incorporates clinical variables with biomarker levels, provides better discrimination of cancer vs. benign processes. 3
THE RATIONALE FOR ORAL CANCER TESTING Early detection can double your chance for survival. 2 Timely diagnosis of oral cancer has been challenging. Early lesions are often not visible, or they mimic other conditions Traditional palpation and visual examination cannot identify occult lesions Current testing options can be cumbersome, costly, and difficult to interpret The fast, simple, and accurate OncAlert Oral Cancer tests can help aid diagnosis at an early stage. 4
EASY TO USE, EASY TO ADD TO YOUR PRACTICE The OncAlert Oral Cancer tests can easily be integrated into your practice for your at-risk patients. Requires no special training or equipment Can be easily administered by clinicians Combines with a visual and physical exam as part of a regular check-up Is simple and painless for patients Provides easy-to-interpret test results Identifies patients who may need additional follow-up The accurate, cost-effective tests can benefit nearly every adult, with particular emphasis on at-risk populations for oral cancer (i.e. current and former tobacco users, those who consume excessive alcohol, or those who may be infected with human papillomavirus). 5
ONCALERT ORAL CANCER RAPID TEST 6
INTRODUCING ONCALERT ORAL CANCER RAPID TEST A SIMPLE, NON-INVASIVE TEST THAT DELIVERS ONSITE RESULTS IN 20 MINUTES The OncAlert Oral Cancer RAPID Test provides a qualitative result, reporting either elevated or normal levels of oral cancer biomarkers. QUICK RESULTS IN JUST 3 STEPS Patient swishes and gargles a sterile saline solution in mouth for 10 seconds Sample is collected in the specimen cup Test cassette is inserted into the specimen cup. Results should be read at 20 minutes The OncAlert RAPID Test helps you easily identify the presence of biomarkers associated with oral and oropharyngeal cancer. Discard test after use. Results may not be valid after 20 minutes. Patients should not smoke, eat, drink or brush their teeth at least one hour prior to testing. 7
ONCALERT: THE SCIENCE OF EARLIER DISCUSSING ONCALERT RAPID TEST RESULTS WITH YOUR PATIENTS If control line does not appear, discard the test and do not use the results. (A positive test is read when either the CD44 OR total protein test strip shows a positive result.) TOTAL PROTEIN OR 1 2 3 4 5 Recommended Threshold Adjusted Threshold CD44 control line test line Negative Positive Test results should be assigned based on either the CD44 or Total Protein gradient scales. A healthcare professional may do one or more of these things: Lesion Test Test Result Result + Test Positive Test Negative With Lesion Take appropriate clinical action Based on clinical feature of lesion may watch and re-examine or biopsy Without Lesion Counsel patient that they have elevated markers Educate that lifestyle changes may decrease marker levels Order OncAlert LAB Test Repeat RAPID Test Routine follow-up This test and suggested guidance is not designed to take the place of clinical findings or healthcare provider judgment. It should only be used as an aid in diagnosis. 8
9 ONCALERT ORAL CANCER LAB TEST
INTRODUCING ONCALERT ORAL CANCER LAB TEST QUANTITATIVE RESULTS THAT SUPPORT CONFIDENT DECISION-MAKING The OncAlert Oral Cancer LAB Test delivers an accurate measure of oral cancer biomarkers Provides a quantitative, personalized result using an algorithm that incorporates important factors such as sex, age, race and tobacco use history Helps support decisions about further diagnostic tests, monitoring, and possible interventions EASY TO USE AND UNDERSTAND Samples are collected in office or clinic for testing at a reference laboratory Point-of-care, patient friendly sample collection Easy administration that fits into your office workflow Quantitative and objective results to aid in the diagnosis of oral cancer 10
ONCALERT: THE SCIENCE OF EARLIER HOW THE ONCALERT ORAL CANCER LAB TEST WORKS This unique test is highly specific and sensitive, with high intra- and inter-assay reproducibility Quantitatively detects all CD44 isoforms and total protein Creates historical, longitudinal profile of patient's oral/oropharyngeal cavity CD44 and total protein levels when incorporated in a follow-up The measurements are reported back to the clinician for use as an aid in diagnosis May reduce the incidence of false negatives compared to a conventional oral exam alone Incorporates clinical variables (e.g. age, sex, race, smoking history) for improved performance May be used following a positive RAPID test to improve discrimination between benign and malignant processes DISCUSSING ONCALERT LAB TEST RESULTS WITH YOUR PATIENTS A healthcare professional may do one or more of these things: Lesion Test Result + Test Positive Test Negative With Lesion Take appropriate clinical action Based on clinical feature of lesion may watch and re-examine or biopsy Without Lesion Additional testing and follow-up Repeat LAB Test Routine follow-up This test and suggested guidance is not designed to take the place of clinical findings or healthcare provider judgment. It should only be used as an aid in diagnosis. 11
KNOWING EARLIER TO GIVE THEM A LATER EARLY FRONTLINE IDENTIFICATION enabling earlier intervention when outcomes are likely to be better ACCURATE the only product line that detects the tumor-initiating and stem cell-associated biomarker CD44 and total protein NON-INVASIVE in-office collection of oral rinse sample for the OncAlert Oral Cancer RAPID Test and the OncAlert Oral Cancer LAB Test COST-EFFECTIVE applicable for a broad range of patients FAST easy-to-interpret results in 20 minutes with OncAlert Oral Cancer RAPID Test Give patients a better later, with the OncAlert Oral Cancer product line. Order today through your local OncAlert Oral Cancer distributor or at www.oncalert.com Sources: 1 WHO 2014-2015 World Cancer Report 2 Pereira LH, Reis IM, Reategui EP, Gordon C, Saint-Victor S, Duncan R, Gomez C, Bayers S, Fisher P, Perez A, Goodwin WJ, Hu JJ, Franzmann EJ. Risk Stratification System for Oral Cancer Screening. Cancer Prev Res (Phila). 2016 Jun;9(6):445-55. References: Head and Neck Cancer, Union for International Cancer Control. 2014 Review of Cancer Medicine on the WHO List of Essential Medicines. World Health Organization website. http://www.who.int/selection_ medicines/committees/expert/20/applications/headneck.pdf?ua=1. Accessed June 25, 2015. Oral cancer facts. Oral Cancer Foundation website. http://www.oralcancerfoundation.org/facts/. Accessed June 25, 2015. Mateus Pereria LH, Reis IM, Reategui EP et al. Risk stratification system for oral cancer screening [published online ahead of print March 28, 2016]. Cancer Prev Res (Phila). 2016. doi: 10.1158/1940-6207.CAPR-15-0200. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108. Mehanna H, Beech T, Nicholson T, et al. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer systematic review and meta analysis of trends by time and region. Head Neck. 2013;35(5):747-755. Why screening works. Oral Cancer Foundation website. http://oralcancerfoundation.org/dental/why_screening_works.php. Accessed June 25, 2015. Petersen PE. Strengthening the prevention of oral cancer: the WHO perspective. Community Dent Oral Epidemiol. 2005;33(6):397-399. Head and neck cancers. National Cancer Institute website. http://www.cancer.gov/types/head-and-neck/head-neck-fact-sheet#q1. Accessed June 26, 2015. Franzmann E, Cowden S, Kim M, Ginn G, Bohannon R. Oral Rinse Test as a Diagnostic aid for oral cancer. J Clin Oncol. 2016; 34 (suppl; abstr e17509) Franzmann EJ, Reategui EP, Pedrosos F, et al. Soluble CD44 is a potential marker for the early detection of head and neck cancer. Cancer Epidemiol Biomarkers Prev. 2007;16(7):1348-1355. Sankaranarayanan R, Ramadas K, Thomas G, et al. Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial. Lancet. 2005;363(9475):1927-1933. Sankaranarayanan R, Mathew B, Jacob BJ, et al. Early findings from a community-based, cluster randomized, controlled oral cancer screening trial in Kerala, India. Cancer. 2000;88(3):664-673. Su WW, Yen AM, Chiu SY, Chen TH. A community-based RCT for oral cancer screening with toluidine blue. J Dent Res. 2010;89(9):933-937. Mehrotra R, Singh M, Thomas S, et al. A cross-sectional study evaluating chemiluminescence and autofluorescence in the detection of clinically innocuous precancerous and cancerous oral lesions. J Am Dent Assoc. 2010;141(2):151-156. Hohlweg-Majert B, Deppe H, Metzger MC, et al. Sensitivity and specificity of oral brush biopsy. Cancer Invest. 2009;27(3):293-297. Elashoff D, Zhou H, Reiss J, et al. Prevalidation of salivary biomarkers for oral cancer detection. Cancer Epidemiol Biomarkers Prev. 2012;21(4):664-672. Carvalho AL, Jeronimo C, Kim MM, et al. Evaluation of promoter hypomethylation detection in body fluids as a screening diagnosis tool for head and neck squamous cell carcinoma. Clin Cancer Res. 2008;14(1):97-107. Neville BW, Day TA. Oral cancer and precancerous lesions. CA Cancer J Clin. 2002;52:195-215. 6301 NW 5th Way Suite 1500 Ft. Lauderdale, FL 33309 info@vigilantbiosciences.com Copyright 2016 by or under license to Vigilant Biosciences, Inc. All rights reserved. Subject to issued and pending international patent protection. All marks used herein are owned by Vigilant Biosciences, Inc. The OncAlert Oral Cancer RAPID Test and the OncAlert Oral Cancer LAB Test are CE Marked and available in select international markets. The OncAlert RAPID Test and OncAlert LAB Test are not yet available for sale in the U.S. BR00-0001-revC