ExonHit Therapeutics hopes to commercialize a microarray-based clinical test for diagnosing Alzheimer's disease in Europe by the first quarter of next year, the company said this week.
It is also in discussions with the US Food and Administration about the best way to submit the in vitro diagnostic for a possible 2012 launch, according to a company official.
Matthew Pando, executive vice president of therapeutics for Paris-based ExonHit, told BioArray News this week that the company hopes to have the test, called AclarusDx Alzheimer's, CE marked by the end of this year, with a European commercial launch at the beginning of 2011.
Pando said the company, which maintains an office in Gaithersburg, Md., is already discussing the test with the FDA, and anticipates that it could become available for clinical use in the US by the first quarter of 2012.
ExonHit launched AclarusDx Alzheimer's in December 2009 for research purposes. The firm claims it can identify individuals with Alzheimer’s disease by screening a blood sample for an internally developed gene signature. So far, the product has been targeted to pharmaceutical companies and academic centers conducting clinical trials for Alzheimer's disease.
Specifically, AclarusDx Alzheimer's is designed to discriminate AD patients from healthy individuals and can be used in association with existing methods to improve patient selection in drug trials, according to the firm. ExonHit says such an improvement in patient selection may translate directly into cost savings and improve trial outcomes.
The Alzheimer's research assay is currently run as a service on ExonHit's Genome-Wide SpliceArray, which is manufactured by Affymetrix. Pando said that ExonHit used this SpliceArray to develop the assay, and that an internally developed algorithm is used to read the signature. As ExonHit gets closer to launching the assay as a test in Europe and later the US, the company anticipates selling AclarusDx Alzheimer's kits to customers.
"As we move forward to CE marking and FDA approval we'll look at having a specific product that just has the signature on it, but we are currently working off the Genome-Wide SpliceArray platform," Pando said.
AclarusDx Alzheimer's is also being developed in parallel with a drug candidate referred to as EHT 202. Pando said that ExonHit, which maintains a therapeutics business and a diagnostics business, has just completed phase IIA trials for the compound, which the firm claims can be used to treat Alzheimer's.
As part of the development of EHT 202, ExonHit is also "running the Genome-Wide SpliceArray platform, which includes the AclarusDx Alzheimer’s signature, against the phase IIA clinical samples to develop signatures that can be used to evaluate performance and to stratify responders versus non-responders," Pando said.
This development of a diagnostic and a drug candidate in parallel is part of a strategy within ExonHit to encourage cooperation between its two business units, diagnostics and therapeutics. "If you look at where large pharma has been moving, you'll see more and more they are looking at companion diagnostics or biomarkers with all their therapeutics programs," Pando said. "We are trying to link our businesses as much as possible to make sure we will utilize all our expertise internally."
Pando said that ExonHit has a specific approach for each sector. "In diagnostics, we want to generate revenues rapidly by acquiring near-to-market products and selling them ourselves or via a partner," he said. "In therapeutics, we want to bring drugs until proof-of-concept and implement new research collaborations."
Sticking with Affy
ExonHit is one of a number of firms that have chosen to use Affymetrix GeneChips as a platform for diagnostics. Other companies that are part of the Santa Clara, Calif.-based array vendor's so-called Powered by Affymetrix program include Roche, Pathwork Diagnostics, Ipsogen, Almac Diagnostics, Skyline Diagnostics, and the Medical Prognosis Institute.
According to Pando, ExonHit has other potential tests in development that will most likely be deployed on the Affy platform. The company has two breast cancer diagnostic assays licensed from Paris' Institut Gustave Roussy. The first of these is a tissue-based test and is to be used following a mammography in association with fine-needle aspiration. The second is a blood-based test and could become an alternative to mammography.
He said ExonHit plans to launch the first assay for research purposes in the third quarter.
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The company has also partnered with bioMerieux to develop tests for colorectal cancer and prostate cancer. The colorectal program aims at identifying specific biomarkers for early-stage detection of colon cancer. ExonHit believes the assay could become an alternative to colonoscopy in the future.
The prostate cancer program similarly aims to identify biomarkers for early-stage prostate cancer diagnosis. Both tests are undergoing clinical validation with preliminary results due next month, according to the firm.
The decision of whether these tests will become available on the Affy platform, though, depends on how many markers compose the final diagnostic signatures, Pando said.
"For all of our programs, the platform we start with is the Affy platform," he said. "The number of probe sets will dictate if we are able to move that to a different platform like qPCR, but for now all of our products are developed on the Affy platform."
ExonHIt chose to use Affy over other platforms because of the firm's SpliceArray design. "It was the only platform where we could fit 6 million probes," Pando said. "We are obviously always evaluating other platforms and how to move to lower-cost platforms, but we are sticking with Affy. It has been IVD approved, and for us it's an easy initial step."
ExonHit said separately last week that it has been chosen to participate in a European Innovative Medicines Initiative consortium called PharmaCog that is focused on identifying biomarkers for Alzheimer’s disease. According to the company, PharmaCog is focused on translational science and harmonization of research tools and should ultimately provide the tools needed to define the potential of a drug candidate and reduce the development time of new medicines.
PharmaCog, which stands for "prediction of cognitive properties of new drug candidates for neurodegenerative diseases in early clinical development," is a cross-party project coordinated by GlaxoSmithKline and the Université de la Méditerranée in Marseille. The program is funded through 2013 by the European Community’s Seventh Framework Programme and has a budget of €20 million ($27.5 million).
William Vickery, head of business development at ExonHit, told BioArray News this week that the firm will apply its Genome-Wide SpliceArray platform as part of its contribution to PharmaCog.
"We will provide access to that platform to identify biomarkers in a variety of preclinical and clinical models for Alzheimer's, looking for blood-based biomarkers that can be linked with disease appearance, progression, and evolution," Vickery said. "Those biomarkers will then be applied to further enhance drug discovery and development in Alzheimer's disease."
ExonHit first launched its SpliceArray platform in 2005. Pando said the platform is still competitive, even as newer technologies, such as next-generation sequencing, are said to provide the means to examine the connection between alternative splicing events and disease.
"With the way we are positioning our products and expertise on that front, we sell the company's expertise and not just a technology," said Pando. "We are not in the business of selling Affy's platform; we sell our expertise and the expertise it takes to analyze the comprehensive data.
"New technologies can produce a lot of data; the trick is to interpret that data and use it to develop a product," Pando added. "That's where our expertise sits. Next-gen sequencing hasn’t been an issue for us."