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Caris Life Sciences Developing New Assays, Planning to Seek FDA Approval for Cancer Profiling Test

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NEW YORK (GenomeWeb) – Cancer molecular profiling company Caris Life Sciences has been working on several new clinical assays and plans to submit its gene panel for approval by the US Food and Drug Administration.

The company, which has been offering tumor molecular profiling services since 2008, is headquartered in Irving, Texas, and has a CLIA-certified and CAP-accredited testing lab in Phoenix, as well as offices in Boston, San Francisco, and Basel in Switzerland. According to David Spetzler, Caris' president and CSO, most of the firm's business currently comes from clinical testing, and some from research for pharmaceutical companies. The firm has distributors offering its testing services around the world, but less than 10 percent of its case volume comes from abroad.

Spetzler said that the company has been distinguishing itself from competitors, who often focus on next-generation sequencing-based testing, by combining several different platforms and technologies, such as immunohistochemistry, in situ hybridization, methylation testing, and NGS. "It doesn't necessarily matter to us what the underlying technology is, as long as there is a clear clinical utility that can benefit the patients," he said.

The company's Caris Molecular Intelligence Comprehensive Genomic Profiling Plus (CGP+) test for solid tumors, for example, analyzes a tumor's DNA, RNA, and proteins. In addition to sequencing a panel of 592 genes, it employs IHC to determine the expression of certain proteins; in situ hybridization to look for deletions, amplifications, translocations and fusions; fragment analysis to detect changes in DNA or RNA; pyrosequencing to detect mutations and methylation; and Sanger sequencing. Spetzler said the company is working on an equivalent test for hematological cancers that is currently in beta testing and available to some of its customers.

Through NGS, the CGP+ test also assesses total mutational load and microsatellite instability of a tumor, and it measures PD-L1 expression by IHC, all to predict a patient's response to immunotherapy. "Certainly, the emergence of immunotherapy has changed everything," Spetzler said. "The fact that we can significantly help patients with metastatic cancer, albeit a small percentage, really gives us hope that we can eventually turn this into a chronic disease."

For example, Caris was involved in a study led by Johns Hopkins University researchers, published in Science in June, which showed that tumors of different origins with high microsatellite instability or mismatch repair deficiency were sensitive to the immunotherapy drug pembrolizumab (Keytruda).

Caris also plans to obtain US Food and Drug Administration approval for its gene panel, following the the agency's recent approval of Memorial Sloan Kettering Cancer Center's MSK-IMPACT assay as an in vitro diagnostic, which paved a regulatory pathway for others to follow.

Spetzler said the company already has approval from the New York State Department of Health, which the FDA accredited as a reviewer, for SNV and indel detection through its 592-gene panel, as well as for its gene fusion assay, and that the department is currently reviewing the panel for microsatellite instability testing. "As soon as New York tells us how [to submit our assay to the FDA], we will do that," he said.

Having an FDA-approved test would lend Caris additional credibility in the market, Spetzler said, and it could be important for pharmaceutical customers wanting to use Caris' panel for clinical trials. "I think it's a really intelligent way to begin to regulate the [laboratory-developed test] market," he said. "There are a lot of ways that you can mess up doing sequencing. Having a degree of oversight there is important, just to protect the patients."

Since 2009, Caris has also been tracking outcomes in a subset of patients and has accumulated data from 20,000 patients so far. To that end, the company has also founded the Precision Oncology Alliance, which involves a number of cancer centers. The idea of this alliance is to aggregate more high-quality clinical outcome data, Spetzler said. "Figuring out what's working and what's not is an ongoing mission and part of what we're trying to do in order to improve patient care as much as possible," he said.

Earlier this year, the company said that the Caris Molecular Intelligence test will be used to profile samples for two studies: the National Cancer Institute's Molecular Analysis for Therapy Choice (MATCH) trial and the American Society of Clinical Oncology's Targeted Agent and Profiling Utilization Registry (TAPUR) study.

Spetzler said Caris has already conducted a concordance study with NCI-MATCH researchers, comparing results from its own test with those from the original NCI-MATCH assay in the same patients. He said that copy number variant detection, in particular, can be tricky, and one goal of the comparison was "to see how much we can rely on each other to find these things." Caris expects to publish the results of the study within the next half year or so.

Both the NCI-MATCH and the ASCO-TAPUR studies also contracted molecular profiling services from Caris' competitor Foundation Medicine. Last month, Caris took legal action against Foundation Medicine by filing a patent infringement lawsuit against the company, claiming that its cancer genomic profiling tests violate several of Caris' patents. Spetzler said that Caris is confident in its IP but conceded that having competitors has not necessarily been a bad thing. "In many ways, Foundation Medicine's success has been good for us," he said. "But it's also about time that they recognize the fact that we started this, and they should acknowledge that."

In terms of reimbursement for the Caris Molecular Intelligence test, Spetzler said that the company has obtained coverage for all cancer types for its multi-gene DNA sequencing panel under a local coverage determination from Palmetto's MolDx program. "We continue to work closely with MolDx to improve access for patients," he added.

Coverage from private payors varies, and can also differ between plans from the same payor. "There is certainly still more work to do there, but it's gotten a lot better, especially this last year," he said.

In addition to its clinical test, Caris has a profiling technology, called Adaptive Dynamic Artificial Poly-ligand Targeting (ADAPT) Biotargeting System, that uses libraries of aptamers — short, synthetic DNA molecules that, like antibodies, bind specifically to certain molecules — to create "fingerprint" profiles for samples with distinct clinical phenotypes. These profiles can be used to distinguish, for example, responders to a drug from non-responders.

Spetzler said the company primarily uses the ADAPT platform for research and pharma services at the moment, for example to discover new drug targets. "We've also built a series of assays to predict who is going to respond to various drugs, some drugs in the trial phase and some drugs already on the market," he said.

In addition, he said, Caris has used the platform to develop liquid biopsy tests. Earlier this year, for example, the company and its collaborators published a study in Scientific Reports in which they used an ADAPT test to distinguish between women with and without breast cancer, based on circulating exosomes in their blood.

Caris has also developed a Herceptin prediction test that uses the ADAPT platform, which Spetzler said might become the first commercially available ADAPT assay. The company is presenting a poster at the San Antonio Breast Cancer Symposium this week showing that the ADAPT assay outperformed standard IHC for HER2 status for differentiating patients who can benefit from trastuzumab (Herceptin) therapy.

Another ADAPT-based assay Caris has been developing is a biopsy support tool for men considering a prostate biopsy. "There is a tremendous amount of biopsies that come back negative. A reduction of those would be very significant for those men," Spetzler said.

In addition, the firm has developed ADAPT tests for pharmaceutical companies "that could take the route of companion diagnostics," he said. "We have some regulatory work to do because you don't know what the target is, you don't know what you're measuring," he explained. "There is an element of a 'black box' with that." He said Caris has already performed a lot of validation work, "so all of the fundamentals in terms of analytical reproducibility are very solid."

The origins of privately funded Caris go to back to the Molecular Profiling Institute, which was founded in late 2004 by the Translational Genomics Research Institute (TGen) and the International Genomics Consortium as a specialty reference laboratory to harness discoveries from the Human Genome Project for cancer patients.

The institute's first assay, Target Now, used proteomic and genomic technologies to profile the tumors of advanced cancer patients in order to identify those who might benefit from specific therapies. At the time, MPI also licensed the MammaPrint assay from Agendia in the Netherlands, making it the sole provider of the test in the US.

Caris Diagnostics, which was originally an anatomic pathology company, acquired MPI in 2008 for an undisclosed amount. In 2011, Caris sold its anatomic pathology business to Miraca Holdings for $725 million and renamed its remaining business, focusing entirely on molecular profiling services and blood-based testing for cancer and other complex diseases, Caris Life Sciences.