About AviaraDx

INTRODUCTION

AviaraDx, Inc. discovers, develops and commercializes molecular diagnostic tests for cancer patients, enabling personalized medicine in oncology. The company operates a CLIA-certified, CAP accredited diagnostic service laboratory in San Diego, CA.

DEFINING THE MEDICAL NEED

In 2007, over 1.4 million new cancer cases were diagnosed in the U.S. alone. Cancer is the number two cause of death in the U.S., killing 560,000 people annually. The NIH estimates the overall cost associated with cancer in the U.S. in 2006 was about $206 billion. Although there has been major progress in the treatment of cancer over the past 20 years, the overall five year survival rate is only 66%. There are many reasons for this high mortality rate, including late diagnosis, challenging tumor identification and classification, and inappropriate treatment, all of which lead to poorer patient outcomes.

THE AviaraDx SOLUTION

The majority of promising new cancer drugs target selected cancer-activated pathways, receptors, and/or enzymes. However, to maximize the clinical utility of these new therapies, it is important to identify the molecular characteristics of each patient’s tumor in order to provide the clinician with optimal diagnostic and prognostic information, along with options for improved therapy regimens. AviaraDx, in collaboration with top tier academic leaders, has developed molecular-based tests that are objective, quantifiable, practical and clinically impactful.

All tests are real time, RT-PCR based, assays that are compatible with readily available, formalin-fixed, paraffin embedded (FFPE) needle core biopsies, excisional biopsies and/or surgical samples.

AviaraDx DIAGNOSTIC OFFERINGS

• Aviara CancerTYPE ID®

Approximately three to five percent of all cancer cases receive diagnoses of “cancer of unknown primary”, or CUP. In addition, a large number of patients receive an “uncertain diagnosis”. Both of these diagnoses pose treatment dilemmas for the oncologist. AviaraDx fills this diagnostic need with the CancerTYPE ID assay, a faster, effective and more objective diagnostic tool that significantly reduces the number of tumors in which the primary origin is diagnosed as either “unknown” or “uncertain”. The CancerTYPE ID assay is proven to have an overall success rate of 87% in classifying 39 cancer types, potentially decreasing time-to-diagnosis and increasing the success rate of cancer classification.

• Aviara H/I^SM (HOXB13:IL17BR)

Studies linking gene expression profiles to clinical outcome in breast cancer have demonstrated that the potential for distant metastasis (i.e., cancer recurrence) and overall survival probability may be attributed to biological characteristics of the primary tumor at the time of diagnosis. Although the majority of breast cancers express estrogen receptor (ER) positivity, approximately 40% of ER+ breast cancers fail to respond, or develop resistance to, endocrine therapy. This leads to disease progression despite adjuvant therapy.

In a genome-wide microarray analysis of tumors from women with ER positive breast cancer treated with adjuvant tamoxifen, AviaraDx, in collaboration with a medical research team at Harvard Medical School, discovered the HOXB13/IL17BR (H/I) gene index, an independent predictor of treatment outcome for breast cancer patients receiving endocrine therapy. Further clinical analysis of nearly 2,700 patients from four independent clinical studies has validated the H/I index as both a prognostic marker, and a biomarker predictive of tamoxifen benefit in ER+ patients.

• Aviara MGI^SM (Molecular Grade Index)

Histological tumor grade is a well-established prognostic indicator of recurrence risk for breast cancer patients. However, there is both subjectivity and inter-/intra-observer variability associated with traditional pathological grading of tumors. In addition, up to 50% of breast tumors are graded as intermediate (i.e., Grade 2), which is not clinically useful for the treating oncologist.

Given the clinical importance of accurate tumor grading, a simple, robust PCR-based assay to quantitatively and objectively assess tumor grade, represents a valuable clinical tool. Aviara MGI is a five-gene tumor grade signature which accurately discriminates between tumor grades 1 and 3 and is able to reclassify Grade 2 tumors as Grade 1-like and Grade 3-like. Patients with Grade 3 tumors have been shown to benefit from chemotherapy.

• Aviara Breast Cancer Index^SM

By combining the results of the Aviara H/I and MGI tests, a combined risk analysis can be calculated for better stratification of ER-positive, node-negative breast cancer patients. This analysis determines a patient’s risk of recurrence based on biomarkers which measure two distinct biological pathways. MGI measures the tumor’s proliferative status, and H/I predicts endocrine benefit. These two biomarkers, when combined, provide a more complete picture of both recurrence risk and therapeutic options for each individual patient.

Unlike other multi-gene assays, the combination of H/I + MGI provides objective information for both the functional status of the ER pathway (H/I) as well as the proliferation status (MGI) within these tumors. Because of this, H/I + MGI has the capability of significantly re-stratifying the majority of “intermediate risk score” patients into either low or high risk groups. This in turn enables the treating oncologist to objectively identify those patients that are in need of, and would most likely benefit from, more aggressive therapies.

PIPELINE

Prognostic Test for Prostate Cancer: Of the 230,000 new prostate cancer cases that are diagnosed each year in the US, about 90% (~207,000) are classified histologically as intermediate grade, with a Gleason score of 6 or 7. This intermediate grade of prostate cancer poses a treatment dilemma for both the clinician and the patient. This test will enable the differential prognosis and treatment pathway selection ranging from “watchful waiting” to surgery and adjuvant therapy.

Predictive Tests for Cancer Drugs: AviaraDx is discovering biomarkers that represent molecular pathways activated in a given cancer that can be inhibited by currently available or development-stage drugs or drug classes. Via its existing internal databases of genome-wide, high resolution expression profiles from more than 1,000 clinical cancer samples, AviaraDx plans to discover and develop a continuous stream of novel diagnostic tests. These tests will be designed to identify treatment pathways and predict responsiveness for specific drugs and/or drug classes.

CLINICAL AND ACADEMIC COLLABORATORS

Harvard Medical School/MGH, Boston, MA; Mayo Clinic, Rochester, MN; MD Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX; and Sharp Memorial Hospital, San Diego, CA.

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