Dec. 21, 2009

TEMPE, Ariz.–Arizona State University will lead a $40.8 million, multi-institutional research program to develop systems that would rapidly measure an individual’s level of exposure to radiation in the event of a radiological or nuclear incident. In the event of a large-scale disaster, such a system would ensure that first responders have the information necessary to provide appropriate medical treatment.

The five-year contract with the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA) emphasizes the development of prototypes that would enable more rapid triage of patients than is currently possible.

“With the proliferation of advanced radiological materials in hospitals, clinics or nuclear facilities throughout the world, the risks and threats of a ‘dirty bomb’ incident or similar nuclear disaster remains very real,” said Carl Yamashiro, PhD, the principal investigator at ASU’s Biodesign Institute who will direct the effort. “We have assembled a dream team of institutions and companies to catalyze our team’s research and discovery efforts, and translate the advances into a field-deployable technology.”

ASU will oversee the research program management, coordination and integration necessary for efficient and effective development of the system.

“Arizona State University has focused its world-class research enterprise on solving many of the most serious problems facing humanity,” said ASU President Michael M. Crow. “This award recognizes our leadership in research that involves the coordinated effort of a large, multi-disciplinary, complex scientific skill set and our capability of delivering on this technological promise to the ultimate benefit of society.”

The development of prototypes incorporates key technologies that build on the research, development and manufacturing strengths of the partners. The effort involves prestigious local and national institutions and companies including: the Translational Genomics Research Institute (TGen), Columbia University, High Throughput Genomics, Inc., Tecan Group, Ltd, University of Arizona, Scottsdale Cancer Research Institute, and the University of Illinois, Chicago.

The goal of the project is to deliver a Biodosimetry Assay System that would assess the amount of ionizing radiation an individual had absorbed in the event of exposure. Currently, no rapid, high-throughput system exists to measure the radiation dose of individuals within a large population.

“The beauty of this system is its versatility,” said Yamashiro. “Not only will we be developing a system for the effective response to a nuclear or radiologic event that could affect a large population but the high-throughput platform can also be used to advance genomics testing and other routine laboratory procedures measuring gene expression levels.”

Developing the system requires utilizing a biomarker signature set based on gene expression markers.

This set of markers will provide a distinct indicator for the level of absorbed radiation. The system will be capable of analyzing 2,000 blood samples in a day with an 8-hour turnaround for individual measurements to enable appropriate medical triage.

The system is designed to be comprehensive in scope, including specialized collection cartridges with which first responders can easily perform field collection of blood samples, a high-throughput assay system, and software for data collection and interpretation of results. The team will also work with government entities including the Food and Drug Administration on the implementation of the system once the prototype has been demonstrated to perform the desired tasks.

The latest effort builds on the achievements of a five-year, $25 million Center for Medical Countermeasures Against Radiation (CMCR), involving research by ASU, TGen and Columbia University. The CMCR was one of eight established by the National Institutes of Health in 2005 in response to increased concerns about radiological disasters from terrorism and illicit trafficking of radioactive materials. The CMCRs conducted foundational research and feasibility studies for such technologies and countermeasures, as well as for related fundamental research for medical options to treat the variety of acute and long-term injuries that can result from nuclear or radiological attacks.

HTG will apply the company’s quantitative nuclease protection assay (qNPA) process to the microarrays to enable researchers to quickly and efficiently measure the gene expression levels in a variety of sample types. The agreement enhances HTG’s existing service capability offering with the ability to take a broader look at gene expression through the multiplex capability of the Roche NimbleGen microarrays. Sample preparation using qNPA technology allows for a much simpler, more cost-effective workflow versus traditional labeling methods, while the Roche NimbleGen multiplex technology offers a cost-effective high density microarray providing in depth gene expression information.

“HTG’s agreement with Roche NimbleGen affords us the opportunity to provide our customers with customizable content and an attractive sample preparation and processing format. Compared with other vendors, Roche NimbleGen was able to offer us unique and differentiated array synthesis and formatting capabilities that best meet our client needs,” said T.J. Johnson, president and CEO, HTG. “The combination of low cost, flexibility, and high throughput means HTG’s customers can derive substantial benefits quickly and we can increase the plex in the analysis process as needed.”

Gerd Maass, CEO of Roche NimbleGen said, “The partnership with HTG showcases the strengths of the two companies and the flexibility of the NimbleGen Arrays by pairing two innovative technologies to provide flexibility, time savings, and cost savings while offering the significant in depth genetic information that our high density arrays provide.”

For more information on Roche NimbleGen microarrays, go to www.nimblegen.com.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients.

In 2008, Roche had over 80,000 employees worldwide and invested almost 9 billion Swiss francs in R&D. The Group posted sales of 45.6 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.

About HTG
Privately-held HTG is based in Tucson, Arizona. Investors in the company include Solstice Capital, Valley Ventures, Merck Capital Ventures, Village Ventures and Arcturus Capital. Additional information is available at www.htgenomics.com.

HTG’s qNPA technology is used to carry out quantitative, multiplexed gene-based drug discovery programs, including target evaluation; HTS lead optimization, metabolism and toxicology. HTG’s platform is highly flexible and designed automation-friendly; it allows scientists to test any sample, including fixed tissues, without RNA extraction or target amplification. The technology is ideal for detecting small, yet important changes in gene expression levels which other gene expression platforms cannot reliably detect.

All trademarks used or mentioned in this release are protected by law.

NIMBLEGEN is a trademark of Roche.

The 96 Max gene expression automated assay is based on HTG’s proven ArrayPlate technology platform, which allows researchers to investigate a larger set of genes with greater precision than traditional gene expression assays. The technology allows academic researchers to quickly and efficiently measure gene expression levels of mRNA and miRNA in a variety of cell and tissue types including formalin-fixed, paraffin-embedded (FFPE) samples.

The technology is ideal for detecting small, yet important changes in gene expression levels which other gene expression platforms cannot reliably detect “HTG’s new assay offering enables our academic researchers, who are conducting clinical and basic research, to essentially unlock information from sample types that were previously very challenging and near impossible to evaluate accurately,” said BJ Kerns, VP Strategic Marketing and Business Development, HTG. “This is yet another expansion of our ArrayPlate platform. We devised this unique testing format to accommodate the needs of academic researchers who are evaluating tumor stratification, pathway and outcome schemes, as well as chemosensitivity.”

About HTG

Privately-held HTG is based in Tucson, Arizona. Investors in the company include Solstice Capital, Valley Ventures, Merck Capital Ventures, Village Ventures and Arcturus Capital. Additional information is available at www.htgenomics.com

HTG’s quantitative nuclease protection assay (qNPA™) is an automated assay that allows
researchers to quickly and accurately measure gene expression levels of mRNA and miRNA in
cells, blood, saliva and tissues with minimal hands-on time. Using HTG’s reagent kits and
equipment, CRL Global Services will evaluate samples or sample plates using HTG’s qNPA
ArrayPlate technology in their CLIA laboratory.

“Collaborating with CRL Global Services was a natural fit for HTG. CRL Global Services has a
strong, long-standing reputation for providing state-of-the-art CLIA testing services. In forging
this relationship, HTG is now able to offer our pharmaceutical, biotech and academic customers
a more seamless and comprehensive service offering,” said TJ Johnson, president and CEO,
HTG. “HTG’s clients are focused on stewarding gene signatures from the research laboratory to
the clinic and CRL Global Services brings a level of expertise in analysis of data that is optimal
for the FDA submission step of the process.”

“CRL Global Services is pleased to be the CLIA-certified laboratory service provider for HTG’s
qNPA technology,” said Tim Sotos, Chairman and CEO of CRL Global Services. “This
collaboration leverages CRL Global Services’ core competency as a leading service provider
and HTG’s robust technology.”

CRL Global Services’ Executive Director of Molecular Diagnostics, Dr. Heather Newkirk said,
“this unique technology from HTG enables a customized gene expression product which
partners well with CRL Global Services’ expertise in offering quality molecular services. We
look forward to working with HTG to provide qNPA services to customers world-wide.”

HTG’s assay technology will be exhibited at CRL Global Services’ Booth #626 at the Molecular
Medicine Tri-Conference in San Francisco from February 25-27, 2009. In addition, Bruce
Seligmann, Ph.D., Founder, Board Member and Chief Science Officer, VP R&D, HTG will be
presenting a talk, “New Generation Predictive Multiplexed Gene Expression Diagnostics: Case
Studies in Non-Hodgkin’s Lymphoma” on Thursday, February 26 at 4:00 p.m.

HTG’s qNPA technology is used to carry out quantitative, multiplexed gene-based drug
discovery programs, including target validation; HTS lead optimization, metabolism, toxicology
and clinical development. HTG’s platform is highly flexible and designed automation-friendly; it
allows scientists to test any sample, including fixed tissues, without RNA extraction or target
amplification. The technology is ideal for detecting small, yet important changes in gene
expression levels which other gene expression platforms cannot reliably detect.

CRL Global Services will offer the qNPA technology as a service to HTG clients in CRL’s CLIAcertified
Molecular Diagnostics laboratory beginning spring 2009.

About HTG
Privately-held HTG is based in Tucson, Arizona. Investors in the company include Solstice
Capital, Valley Ventures, Merck Capital Ventures, Village Ventures and Arcturus Capital.
Additional information is available at www.htgenomics.com.

About Clinical Reference Laboratory, Inc (CRL Global Services)
Established in 1979, CRL Global Services is a privately held reference laboratory in Lenexa,
Kansas offering leading-edge testing services in the areas of Clinical Trials, Corporate Wellness
Programs, Genomics, Insurance, Molecular Diagnostics, BioAnalytics and Toxicology. CRL is
one of the largest single-site laboratories in the country and analyzes over 80 million tests
annually. Additional information is available at www.crlcorp.com.

Tucson, Ariz.—December 1, 2008—HTG, Inc., provider of the quantitative Nuclease Protection Assay (qNPA™) system and service partner for the life sciences industry, today announced a collaboration agreement with researchers at Harvard Catalyst Laboratory for Innovative Translational Technologies (HC-LITT) at Harvard Medical School. Under the terms of the agreement, HTG and HC-LITT will collaborate to generate a novel microRNA biogenesis assay that can measure expression of both pre-microRNA (miRNA) precursors, mature-microRNAs and regulated RNA using HTG’s qNPA™ (quantitative Nuclease Protection Assay) technology.

Researchers at the HC-LITT are investigating the implications of differential microRNA expression in human diseases such as cancer. MicroRNAs are singlestranded functional RNA species encoded in the human genome that regulate protein expression of numerous gene products. HC-LITT will utilize HTG’s technology to evaluate regulation of miRNA biogenesis by established oncogenic cell signaling pathways in order to develop novel diagnostic markers and therapeutic targets for the molecular characterization and treatment of cancer.

“We selected HTG’s technology due to the high precision and sensitivity of the product platform,” said Winston Patrick Kuo, Director, Harvard Catalyst Laboratory for Innovative Translational Technologies at Harvard Medical School. “I’m looking forward to utilizing HTG’s gene expression assay technology and imagers for HC-LITT’s research initiatives.”

HTG’s qNPA technology is used to carry out quantitative, multiplexed gene-based drug discovery programs, including target validation, HTS lead optimization, metabolism, toxicology and clinical development. HTG’s platform is highly flexible and designed for high throughput automation; it allows scientists to test any sample, including fixed tissues, without RNA extraction or target amplification. The technology is ideal for detecting small yet important changes in gene expression levels which other gene expression platforms cannot reliably detect.

About Harvard Catalyst Laboratory for Innovative Translational Technologies
The Harvard Catalyst Laboratory for Innovative Translational Technologies (HC-LITT) is scaling existing infrastructure to support translational research by providing early access to enabling, leading-edge genomic and proteomic technologies. The goal of the HC-LITT is to facilitate innovative, technologic contributions to novel translational research. The development of unique methods is pivotal to identifying nascent methodologies to diagnose and treat human disease. The collaborative research model is designed to bring together a myriad of innovative technologies in one place and put them to use in the hands of inventors and thought leaders.

About HTG
Privately-held HTG is based in Tucson, Arizona. Investors in the company include Solstice Capital, Valley Ventures, Merck Capital Ventures, Village Ventures and Arcturus Capital. Additional information is available at www.htgenomics.com.

Tucson, Ariz.—November 24, 2008— HTG, Inc., provider of the quantitative Nuclease Protection Assay (qNPA™) system and service partner for the life sciences industry, today announced it has appointed Fredrick L. Pollock to Vice President of Corporate Development. Pollock will be responsible for leading commercial sales efforts in the academic and research markets, spearheading efforts for bio-marker and signature discovery collaborations and supporting commercialization efforts for the company’s mid-density array product line.

Over the past eight years, Pollack has served in management, sales and business development roles most recently as Director of Strategic Businesses and Translational Medicine at Affymetrix, Inc., a leading microarray technology vendor. His accomplishments include implementing a global alliance management program, developing strategies for sales expansions, launching several partner clinical laboratory improvement amendments (CLIA) certified clinical tests, and securing multi-millions in additional sales.

“Fred brings a wealth of industry knowledge and expertise to our leadership team and he will help us accelerate our commercial and corporate development efforts,” said TJ Johnson, President and CEO, HTG. “HTG’s portfolio strategy is to leverage the precision of the qNPA assay into the mid-plex market and establish the assay as a new standard for gene expression based diagnostics. Fred’s background is perfectly suited to help us in these specific areas.”

“I am eager to work with the HTG management team and build on the proven success of HTG’s platform to further expand the company’s customer base,” said Fred Pollock. “With my biotechnology and translational medical industry experience this was an ideal fit. I look forward to contributing to HTG’s future success in my new capacity.”

Prior to Affymetrix, Pollock worked at Amersham Pharmacia Biotech, now part of GE Healthcare, for 11 years. He most recently served as a business unit manager where he was responsible for managing sales in the central United States. He also held positions at The University of Texas Southwestern Medical Center and Photon Marketing.

Pollock earned a B.A. in Molecular Biology from the University of North Texas. HTG’s qNPA technology is used to carry out quantitative multiplexed, gene-based drug discovery programs, including target validation, HTS lead optimization, metabolism, toxicology and clinical development. HTG’s platform allows scientists to test any sample, including fixed tissues, while avoiding the need for extraction or target amplification. The platform provides high-quality quantitative test results enabling clients to compress drug discovery and development program timelines, increase program success and reduce costs.

About HTG
Privately-held HTG is based in Tucson, Arizona. Investors in the company include Solstice Capital, Valley Ventures, Merck Capital Ventures, Village Ventures and Arcturus Capital. Additional information is available at www.htgenomics.com.

Applications
FFPE Tissue in the qNPA ArrayPlate System
miRNA in the qNPA Arrayplate

Brochures
High Throughput Gene Expression Analysis
Measuring miRNA with qNPA Technology 

Instruments
Capella Imager
Omix II Imager

Products
qFix qNPA ArrayPlate

Drug Discovery

Applications
FFPE Tissue in the qNPA ArrayPlate System
miRNA in the qNPA Arrayplate

Brochures
Multiplexed Biomarker-Driven Drug Discovery
Measuring miRNA with qNPA Technology 

Instruments
Omix HD Imager

Products
qFix qNPA ArrayPlate

In most fixed tissue specimens, the majority of RNA is cross-linked to cellular material, much of which is insoluble and is therefore resistant to RNA extraction. qNPA oligonucleotides can hybridize to these tissue-bound RNAs and the nuclease protection assay can proceed as normal.

As the image to the left shows, a significantly larger amount of signal is obtained from the FFPE samples (column A) which include the pellet material in the qNPA process. This is distinctly different from the fresh tissue control (column B), where the material is fresh frozen and RNA is readily soluble in the supernatent. Only qNPA technology can access the bound, cross-linked RNA in FFPE that RNA extraction techniques cannot recover, providing an advantage over other gene expression techniques.

How much FFPE material do I need to use per well?

It depends on the sample, the transcripts being measured, and the cell density, but typically a 2 X 3 cm portion of a 5µm tissue section is sufficient for strong signal. More tissue may be needed if samples are to be run in duplicate or triplicate. Sample requirements for other fixed cell preparations may vary, contact us for more information.

Can I do qNPA testing on slides that have already been stained?

It depends on the stain and the protocol.  H & E stained slides have been used to obtain gene expression results identical to those of matched unstained slides. Other stains and staining protocols may be acceptable if they do not damage the RNA through high temperatures or metal ion deposition. HTG can test your stained slides to see if they work with qNPA technology.

How do I prepare the FFPE material?

Unlike most techniques which require tedious and expensive preparative steps, qNPA requires the researcher only to scrape the section of fixed tissue off the glass slide and into a tube containing the qNPA Lysis Buffer. The sample is then overlain with oil, heated, and the qNPA protocol proceeds as outlined here.

Do I need to remove the paraffin from my samples?

No. Any paraffin in the samples is melted during incubation in our Lysis Buffer and will float to the surface of the sample well. The oil overlay used to prevent evaporation during this step will effectively remove any molten paraffin. qNPA does not use xylene or other volatile organic solvents.

Does HTG provide CLIA testing services?

HTG has recently partnered with Clinical Reference Laboratory of Lenexa, Kansas to provide CLIA certified testing with qNPA products. Please contact your local HTG sales representative for further information.

How does gene expression analysis by qNPA technology compare to IHC staining?

Very well. Individual tissue slices were stained and examined for the presence of BCL-6. The signal obtained from qNPA (chart) correlates well with the IHC staining.

Are there references for the use of qNPA to analyze FFPE?

Roberts, R., Sabalos, C., Martel, R., et al, ( 2007). “Quantitative Nuclease Protection Assay in Paraffin-Embedded Tissue Replicates Prognostic Microarray Gene Expression in Diffuse Large-B-Cell Lymphoma” Laboratory Investigation, 87: 979-997.

Rimsza, L., LeBlanc, M., Unger, J., et al., (2008). “Gene expression predicts overall survival in paraffin embedded tissues of diffuse large B cell lymphoma treated with R-CHOP” Blood, Online June 10, 2008 doi: 10.1182/blood-2008-02-137372.

Please contact our technical support with any further questions!