ChipDX.com

IntroductionChipDX is a start-up company founded in 2008 that develops, validates and delivers In-Vitro Diagnostic Multi-Index Assays (IVDMIAs). This emerging class of diagnostic tools has the potential to address many areas of unmet clinical need. IVDMIAs represent an integration of high-throughput genomic profiling, machine learning and an increased understanding of the molecular basis of cancer. ChipDX is bringing a new level of analytical transparency, quality control, universal access and result interpretation to the field of molecular diagnostics.

Designed for AffymetrixThe ChipDX web platform for multi-gene diagnostic analysis has been designed for compatibility with the Affymetrix GeneChip platform. Versions of this industry-standard genomic analysis system are available for research and clinical use and can be used with tissues preserved in a variety of formats.

ChipDX’ online analysis platform embodies the Affymetrix goal of moving applications downstream from the basic research markets into clinical applications to vastly improve diagnosis and lead to better informed decisions for the most common cancers.

Kevin Cannon, Vice President of Marketing, Gene Expression Applications, Affymetrix

Accomplishments to date:Since 2008, ChipDX has created and validated novel multi-gene, prognostic signatures for breast, colon and (non-small-cell) lung cancer. A diagnostic gene expression signature for performing molecular characterization of metastatic and poorly-differentiated tumors has also been developed.

The multi-step automated GeneChip Quality Module, a component part of the ChipDX online gene expression analysis system, has been specifically designed for assessing the quality of genomic data intended for clinical use.

1. Colon CanCer Module

Clinical need: Treatment of patients with early stage colon cancer is controversial, with current methods for evaluating a patients risk of relapse resulting in high rates of over and under-treatment. There is a need more individualized methods of predicting recurrence and selecting patients for adjuvant chemotherapy.

novel development:The ChipDX multi-gene signature for colon cancer identifies individuals with early stage colon cancer who are at high risk of disease recurrence within 5 years and may therefore benefit from standard adjuvant chemotherapy.

Designed for scalability • Parallelprocessingdesignallows

unlimited processing capacity• Additionalmodulescanbeadded

via online Module Designer interface or in consultation with ChipDX development team.

Designed for ease-of-use • GeneChip CEL file upload automatic

from scanner• Emailnotificationwhenanalysis

complete• Onlinetrainingandsupport

Designed for accuracy• Multi-gene signatures developed from

large, multi-center patient series• Allalgorithmsvalidatedon

independent patient series, not used in gene selection or assay development

• Assessmentsofinter-laboratoryvariation made and incorporated into result output

Designed for security• E ncrypted web server, databases, backup and data-transfer• Serverslocatedinstate-of-the-art

enterprise class data center• HIPAA-compliantuseraccesspolicies• Fullaudittrails

“

”

ChipDX’s multivariate method of gene selection identified 163 genes with expression patterns correlated with patient outcome, independent to clinical outcome predictors.

Kaplan Meier analysis of the cross-validated colon cancer training series and independent validation series, as classified into high and low risk groups according to the ChipDX 163 gene prognostic signature

The signature was validated on an independent series of 60 stage II and III colon cancer patients and it’s ability to classify patients into high or low risk groups for recurrence and overall survival was confirmed.

This ChipDX test was published in the November 2010 edition of the British Journal of Cancer (103, 1852–1857).

2. Breast CanCer Module

Clinical need: Accurate information about a breast cancer patients’ risk of recurrence can assist clinicians in tailoring treatment options to each individual.

By developing a cost-efficient method of performing multi-gene prognosis prediction, ChipDX aims to increase the proportion of breast cancer patients able to incorporate personalized genomic screening into the management of their disease.

novel development:A 200-gene signature was identified using multi-variate methods of analysis on a series of 477 breast cancer genomic profiles. This algorithm was shown to predict a patients likelihood of recurrence and over all survival for up to 10 years

and was validated on an independent series of more than 1,000 patients from multiple treatment centers.

A manuscript describing the development and validation of this ChipDX signature has been reviewed and accepted for publication by the Journal of Molecular Diagnostics, the official publication of the Association for Molecular Pathology.

3. lung CanCer ModuleClinical need:There is an urgent need for methods to identify early stage patients with poor prognosis. Prognostic algorithms for NSCLC have been published over the past decade, however none offer a significant improvement over risk-stratification based on clinical parameters alone.

novel development:A multivariate gene selection approach has been identified from a series of 330 lung adenocarcinoma profiles. The 160-gene signature identified is being validated on an independent series of 398 patients. Expanding beyond outcome prediction, a panel of gene expression indicators that may assist in predicting response to a number of targeted therapies is also being developed.

4. tuMor origin Module Clinical need:Difficulty in diagnosing metastatic or poorly differentiated tumors can result in expensive, invasive and time-consuming diagnostic investigations. Patients in which the primary origin of a tumor cannot be identified using traditional means are often faced with limited treatment options and extremely poor survival times.

novel development:This module compares the genomic profile of the metastatic or poorly-differentiated tumor to a large database of molecular information from tumors with known origins. This test has been validated on more than 1,000 primary tissues and 200 metastases. The identified results have been in 89-94% agreement with clinical diagnosis. This is used as an additional Quality Control step for other primary-tissue modules.

5. geneChip Quality Module Clinical need:Before analyzing a patient’s genomic profile, the accuracy and reproducibility of the data must be determined. There is no widely-accepted standard for performing quality control analysis on genomic data intended for clinical use.

novel development:BasedonexperiencewithISOandFDAstandardsforclinicalgene expression analysis, this module comprises a series of automatic data quality and reliability assessments. The areas of analysis include background, non-specific hybridization, replicate variation, signal-to-noise ratio and a comparison of housekeeping gene expression to carefully predetermined control values.

Kaplan Meier analysis of a 395 patient breast cancer series classified as high or low risk according to the ChipDX 200 gene breast cancer signature. Patients classified as low risk have an excellent prognosis of >90% survival for up to 10 years following diagnosis.

Mission Statement

• Providecliniciansallovertheworldwith direct access to the latest diagnostic, prognostic and predictive ‘omic’ algorithms.

• Contributetocreatingastandardizedmethodology for assessing the quality and reliability of genomic data for clinical use.

• Provideacloud-basedprocessingengine for 3rd party pharmaceutical & diagnostic companies enabling rapid IVDMIA development and delivery.

• Facilitateintegrationofgenomicanalysis into clinical practice using existing and emerging technology platforms.

ChipDX Road Map 1. Establish clinical collaborations

to plan and perform additional validation studies of genomic assays for breast, lung, colon cancer or tumor characterization.

2. Establish partnerships with academic groups or pathology services

3. Adapt signatures to formalin-fixed paraffinembedded(FFPE)tissue.

4. Create custom ChipDX Affymetrix GeneChip, manufactured under appropriate conditions for diagnostic use.

5. WorktowardsobtainingFDAclearance,ISOcertificationandCE-markingofChipDX services and GeneChip and reagents.

6. Engage diagnostic assay developers for ChipDX Module Designer beta testing program.

6. ChipdX autoMated Module designer

industry need:A secure, standardized and customizable genomic data analysis system is needed to facilitate regulatory agency clearance and bring diagnostic services to market in less time and at reduced development costs.

ChipdX novel development: The ChipDX online delivery system includes

• CELUploadModule(normalization,probeannotation)

• QualityControlModule(withcustomizablethresholdsandcontrols for specific genes)

• Tissue-typeConfirmationModule(ensureprofile matches correct tissue type, confirm malignancy)

• CustomizedReportingModule(customizableoutputs)

ChipDX Consulting ServicesChipDX can develop complete multi-gene signature from proprietary or public genomic datasets on a fee-for-service basis. We can also assist in validation work, statistical analysis, performance comparisons and algorithm stabilization. All algorithms developed can be completely stand-alone or integrated into the ChipDX Analysis System.

ChipDXiscurrentlyavailableforlimitedresearch-useonly(RUO)|ChipDXLLC

To evaluate ChipDX (free) please sign up at www.ChipDX.com

Email: info@chipdx.com Phone: (347) 857-9415 Twitter: @chipdx

Clinician

Biopsy

AnalysisModule

Genechip

QualityModuleduledduled

UploadData

Report

Doctor & Patient

AnalysisModule