SaliMark™ OSCC Investigator Meeting Salivary Transcriptome Markers for Oral Squamous Cell Carcinoma Detection SaliMark™ OSCC

Study Organization Sponsor: PeriRx, LLC Chief Medical Office – Dr. Jack Martin CEO – Stephen M. Swanick PI: Dr. Marc Surkin Statistician/Regulatory Consultant: Dr. Richard Chiacchierini Former Director FDA IVD

SaliMark™ OSCC NIH & Salivary Dx: Vision & Investments By 2013, determine the efficacy of using salivary diagnostics to monitor health and diagnose at least one systemic disease.

SaliMark™ OSCC Tumors are known to produce mediators (hormones/cytokines/lymphokines) that can modulate the activities and gene expression patterns of distal organs (salivary glands) through the vasculature.

SaliMark™ OSCC Subsequently verified in multiple ethnic groups before National Cancer Institute – Early Detection Research Network Study mRNA Markers for OSCC Initially Discovered 2004

SaliMark™ OSCC Conclusions: The validation of these biomarkers showed their feasibility in the discrimination of OSCCs A prospective blinded trial was necessary 395 subjects studied by National Cancer Institute – Early Detection Research Network

SaliMark™ OSCC Study Population (n=168) – 71% of patients with T1/T2 lesions Highly statistically significant increase in all six pre-specified mRNA markers (DUSP1, OAZ1, SAT, IL1B, IL8 and S100P, p <0.001 for all) 2 – nearly 4 fold increased levels Five of 6 mRNAs significantly upregulated in dysplasia Prior NCI Multi-marker Model Validated New Highly Discriminatory Multi-marker Models Developed in Intended Use Population of Patients with Suspicious Oral Lesions Test score is based on a weighted average of the expression of 3 cancer genes relative to “housekeeping” genes – “gene expression footprint” PeriRx Prospective Blinded Validation Study

SaliMark™ OSCC Study Population (n=168) – 71% of patients with T1/T2 lesions Highly statistically significant increase in all six pre-specified mRNA markers (DUSP1, OAZ1, SAT, IL1B, IL8 and S100P, p <0.001 for all) 2 – nearly 4 fold increased levels Five of 6 mRNAs significantly upregulated in dysplasia Prior NCI Multi-marker Model Validated New Highly Discriminatory Multi-marker Models Developed in Intended Use Population of Patients with Suspicious Oral Lesions Test score is based on a weighted average of the expression of 3 cancer genes relative to “housekeeping” genes – “gene expression footprint” PeriRx Prospective Blinded Validation Study 71% of patients with T1/T2 lesions Over 800 subjects enrolled in Clinical Trials of SaliMark™ OSCC Biomarkers

SaliMark™ OSCC How to Use the SaliMark TM OSCC Test Score Lesion Suspicious For OSCC Low Risk Test Score: Follow Up Within 4 Weeks Low Risk Test Score: Follow Up Within 4 Weeks Moderate Risk Test Score: Second Opinion from Specialist* Moderate Risk Test Score: Second Opinion from Specialist* High Risk Test Score: Refer for Consideration of Biopsy High Risk Test Score: Refer for Consideration of Biopsy SaliMark TM OSCC Test *Specialist decision on biopsy and follow up to be based on quantitative test score, physical examination and risk factors in medical history (smoking, alcohol consumption, age, gender and ethnicity) The goal of salivary testing Is to get appropriate patients to specialists sooner

SaliMark™ OSCC Dual Approval Pathway - We Need Additional Cases! Current data supports CLIA Approved Laboratory Developed Test Additional cases necessary to support FDA submission

SaliMark™ OSCC Getting started Online CITI Program training course on ethical issues in research required by IRB for one investigator in each practice Sign financial disclosure statement Sign contract with PeriRx, LLC

SaliMark™ OSCC Inclusion Criteria 18 years and older Oral lesion requiring biopsy Recently diagnosed OSCC not as yet treated Enrollment as easy as spitting in a cup Diagnosis of cancer within the last 5 years, excluding non-melanoma skin cancer or OSCC within 2 years If > 5 years since other cancer diagnosis, must be free of known disease & not on current treatment for cancer Prior Immunosuppressive therapy (in last 2 months) or current autoimmune disorder HIV or Hepatitis (in last 2 months) Exclusion Criteria Enrollment Tips Review practice schedule on Fridays for potential cases Alert Priority Express Courier at (Available 24/7/365) OR if scheduled in advance at Account Name: PeriRx, Account # Physician support for the importance of this trial is key to successful enrollment Stress the noninvasive/painless nature of the study, the absence of risk and the benefits Just Do It! – once you enroll the first patient the rest is easy

SaliMark™ OSCC The patient should fast for 1 hour Have the patient rinse their mouth with water Collect 2 cc of saliva into Falcon tube (to top of cone section) Label the tube with provided waterproof label The specimen is identified by the study ID (for example - Surkin 001, 002, etc.) Place the capped tube in bag with ice Call the courier service Saliva Collection Steps

SaliMark™ OSCC Conclusions We Need Additional Subjects for an FDA Submission