AutoGenomics, Inc. COMPANY PROFILE. For reprint orders, please contact:

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2 For reprint orders, please contact: COMPANY PROFILE AutoGenomics, Inc. Ram Vairavan Vice President, Marketing & Business Development 2270-K, Camino Vida Roble Carlsbad, CA 92009, USA Tel: ; Fax: ; Keywords: BioFilmChip microarray, biomarkers, disease management, genomics, multiplexing platform, load & go, molecular diagnostics, multiple drug resistance, pharmacogenomics, proteomics AutoGenomics has created an automated multiplexing microarray platform to make genomic and proteomic analyses routine and efficient for clinical and research laboratories. While the emergence of microarrays has advanced genomic analyses, a number of underlying issues, such as cross-hybridization, poor spot morphology and intrinsic fluorescence of the solid substrate, have yet to be fully resolved. Current methods use discrete instrumentation, are manual and require highly skilled labor, which leads to inconsistent results. AutoGenomics automated platform uses a three-dimensional BioFilmChip TM microarray to circumvent these issues, providing optimal spot morphology and utilizing solution-based hybridization with allele-specific primer extension to improve single-base discrimination. AutoGenomics is developing applications for the early detection and management of complex disease states in oncology, cardiology, and mental disorders. Customers include clinical reference laboratories, hospitals, academic institutions, and pharmaceutical and biotech companies. Founded in 1999, the company is headquartered in Carlsbad, California, USA. Introduction Genomics and proteomics research are creating innovative, groundbreaking discoveries that are changing the way diseases are diagnosed, monitored, and managed. As a result, physicians must have the ability to closely monitor the progression of disease with a unique signature of genomic and proteomic markers. This will enable them to make an informed decision on diagnosis and therapy. Targeted therapeutics are being developed to address specific protein products of these genes. One such example is trastuzumab (Herceptin ; Genentech, Inc.), which is a drug used to treat breast cancer and targets the protein product of the HER2 gene. The efficacy of the drug in treating patients with metastatic breast carcinoma is predicted by the overexpression of HER2/neu protein, thus making it a valuable test in the management of breast cancer. Auto- Genomics is capitalizing on this transformation. System solution AutoGenomics multiplexing microrarray platform, the INFINITI Analyzer, seamlessly brings genomic and proteomic samples into the realm of automated molecular testing; thus, this platform enhances lab work flows by delivering sample to result without manual intervention. The INFINITI Analyzer, therefore, offers the following distinct benefits to the user: Multiplexing capabilities; given that most diseases are caused by multiple genetic mutations and/or protein expressions, the ability to multiplex multiple markers on the same microarray enhances productivity and workflow. Genomic and proteomic analyses; a single platform to perform both genomic and proteomic analyses. Fully integrated platform; integration all of the discrete processes in genetic analyses such as fluidics, hybridization, stringency, optical detection and result analysis into a selfcontained platform. Lower requirement for skilled labor; the load and go design allows the system to be operated by less skilled laboratory technicians in contrast to the highly skilled individuals needed to perform manual genetic tests. Compelling economics; enhanced productivity and work flow provides a cost-efficient solution. The key components are shown in Figure 1 and include the BioFilmChip microarray, the Intellipac reagent management module, the INFIN- ITI Analyzer and Qmatic Operating Software. The BioFilmChip microarray The BioFilmChip microarray is based on a polyester film coated with proprietary multilayered matrices. It minimizes background fluorescence and provides significant performance and cost advantages over traditional microarrays. The BioFilmChip microarrays are offered as ready-to-use microarrays, preloaded 2004 Future Medicine Ltd ISSN Pharmacogenomics (2004) 5(5),

3 COMPANY PROFILE Vairavan Figure 1. Components of the INFINITI multiplexing microarray platform. A. C. B. A. The BioFilmChip microarray. B. The Intellipac reagent management module. C. The INFINITI Analyzer. with immobilized probes for clinical use and are customizable for research, life sciences and clinical trial applications. The Intellipac reagent management module The Intellipac reagent management module is a unique reagent management system that contains all of the necessary reagents to perform a test. The on-board microchip efficiently manages the reagents, electronically records all relevant reagent specific information, such as expiration date, reagent usage and operator usage data, and contains the assay protocol for a specific test. The INFINITI Analyzer The INFINITI Analyzer is a plug-and-play platform that integrates all of the discrete processes of sample handling, reagent management, hybridization, detection and result analysis of DNA and proteins. The analyzer has been designed to operate on a load-and-go concept. In order to run a test, the operator generates a work list, loads the samples, BioFilmChip microarrays and Intellipac reagent modules, and then walks away. The tests are processed automatically and read by the built-in confocal microscope. Results are analyzed and presented in a customized graphical format for easy interpretation. The used chips are discarded in the waste drawer for easy disposal. The system can process 24 microarrays simultaneously. Qmatic Operating Software Qmatic Operating Software is a proprietary software module built into the INFINITI Analyzer. It manages multiple processes in genomic and proteomic analyses. The Qmatic software s random access capability allows the INFINITI Analyzer to simultaneously manage multiple tests with different methodologies on a continuous flow basis. Open architecture design The INFINITI Analyzer s open architecture design enables adaptation of multiple methodologies, such as hybridization assay, allele-specific primer extension assay to perform single nucleotide polymorphisms (SNPs), short tandem repeats (STRs), microsatellite analysis, and gene expression analysis. Without any modification, the same platform can be used to perform protein determinations using sandwich, competitive and enzymatic methodologies. Furthermore, the analyzer permits users to develop protocols for their own applications. Emergence of molecular diagnostics Advances in understanding disease at a molecular level are facilitating the treatment of individuals based on their genetic make-up rather than symptoms. This is leading to the development of new diagnostic tests. Genetic mutations of diseases, such as cystic fibrosis and Tay-Sachs, can now be positively identified at birth. To facilitate 586 Pharmacogenomics (2004) 5(5)

4 AutoGenomics, Inc. COMPANY PROFILE early treatment, better management and reduce healthcare costs, many states have begun the mandatory screening of a number of inherited genetic disorders, including cystic fibrosis. Although newborn screening and genetically inherited disease detection are the current focus of research, disease management is becoming the key driver for future growth. Recent advances in genomic and proteomic research have uncovered numerous gene and protein targets that are leading indicators of major diseases, including cancer, cardiovascular and psychiatric disorders. These complex disease states have multiple gene and protein markers that offer information on the presence and progression of a particular disease. Molecular diagnostics has a number of applications for disease management, including: Early diagnosis; early identification of genetic mutations and structural abnormalities in proteins will enable early diagnosis and risk stratification of specific disease states, leading to administration of proactive treatment protocols. Pharmacogenomics; characterization of the body s interaction with pharmaceuticals at the molecular level will assist in the choice of treatment options, increase the awareness of interactions among multiple drugs, and allow physicians to prescribe more customized dosages for each patient. Theranostics (therapy and diagnostics); creation of tests that can identify which patients are most suited to a particular therapy and providing feedback on how well a drug is working in order to optimize treatment regimens. Wide spectrum of applications AutoGenomics is developing a wide spectrum of applications in genetic disorders, pharmacogenomics, biomarkers in oncology, infectious diseases, cardiology and mental disorders. The company has completed the development of genetic tests to determine mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) genes, as well as tests for identifying factor II, factor V Leiden and methylenetetrahydrofolate reductase (MTHFR) mutations. The ability to multiplex several markers on the same chip has enabled the company to make progress in developing a novel genotyping assay for the accurate determination of high- and lowrisk human papillomavirus (HPV) types. Ideally, an HPV test should allow for the detection of multiple HPV types, identify individual types, Highlights Multiplexing microarray platform that addresses DNA-, protein- and cell-based assays. Degree of automation that eases requirement of skill level. Film-based microarray that provides ideal spot conformity and multiplexing capabililty. Wide spectrum of applications in genetic disorders, pharmacogenomics, oncology, infectious diseases, cardiology and mental disorders. and provide quantitative information about the viral load of each individual type found [1]. The increasing importance of pharmacogenomics is now being realized by the drug industry. The cytochrome P450 2D6 (CYP2D6) enzyme is involved in the metabolism of tricyclic antidepressants, antipsychotics, β-adrenergic blockers, and antiarrhythmics, and it is believed to be responsible for > 70 different drug oxidations. The deficiency of the CYP2D6 enzyme is inherited as an autosomal recessive trait with 7% of Caucasians classified as poor metabolizers [2]. Since there may be no alternate metabolic pathways to clear these drugs from the system, poor metabolizers may be at severe risk from adverse drug reactions. AutoGenomics is developing a CYP2D6 test and will complement it with CYP2C9 and CYP2C19 tests to enhance patient care. Outlook: assessing multi-drug resistance Multi-drug resistance (MDR) is a major problem in the treatment of cancer with chemotherapy. MDR generally occurs when the cancer cells transport certain chemotherapeutic drugs from inside their cell to the outside. Such resistance can occur, for example, if there is an overexpression of the trans-membrane permeable glycoprotein, which appears to act as a drug efflux pump, inhibiting the rise in the intracellular concentration of anticancer drugs. The diagnosis of potential drug resistance (whether single or multiple) is, therefore, a critical step in determining which form of chemotherapy is likely to be most effective. Administering an ineffective drug can cause chemotoxicity in the patient, which leads to adverse side effects and impedes timely treatment. With its ability to multiplex and perform DNA and protein assays simultaneously, AutoGenomics is working with academic and research institutions to develop MDR applications for use with cancer and antiretroviral drugs

5 COMPANY PROFILE Vairavan AutoGenomics plans to use its versatile platform as a valuable tool to screen for biomarkers in personalized medicine. Biomarkers of disease play an important role in drug discovery and development by providing clues to genetic susceptibility, disease progression and predisposition, as well as offers information on physiologic and metabolic profiling of diseases [3]. The availability of these new-wave markers has played a key role in improving the time and cost-efficiency of drug development, as well as providing tools for early disease detection, prognosis, and monitoring. AutoGenomics also plans to develop DNA fingerprinting and agricultural applications. Bibliography 1. Iftner T, Villa LL: Chapter 12: human papillomavirus technologies. J. Natl. Cancer Inst. Monographs 31, (2003). 2. Bertilsson L, Dahl ML, Dalen P, Al-Shurbaji A: Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br. J. Clin. Pharmacol. 53(2), (2002). 3. Colburn WA: Biomarkers in drug discovery and development: from target identification through drug marketing. Clin. Pharmacol. 43, (2003). 588 Pharmacogenomics (2004) 5(5)