Signature Genomics is planning additions to its newly launched oncology-testing services and is eyeing a move into neuropsychiatric testing, according to the firm's top official.
Co-founder and President Lisa Shaffer said last week that the Spokane, Wash.-based company believes the market for oncology testing could be several times that of testing for postnatal genetic abnormalities, for which the company currently offers tests.
Signature plans to roll out several new cancer-testing indications by the end of the year.
Shaffer added that the company's array platform already contains the requisite content for neuropsychiatric testing, and that Signature is exploring avenues to promote its service in that market.
"The reason that we developed Signature Genomics in the first place was that we felt we could do a better job with arrays than with traditional chromosome analysis," Shaffer said. "We started with mental retardation [testing] because it was my experience and what I was interesting in," she said, "but oncology is a natural extension."
Shaffer spoke with BioArray News during Signature Genomics' Scientific Microarray Conference, held in Spokane last week.
Founded in 2003 by Shaffer and Chief Medical Officer Bassem Bejjani, both formerly of Baylor College of Medicine, Signature launched array comparative genomic hybridization-based tests for postnatal genetic abnormalities in 2004, and rolled out prenatal testing in 2007 (BAN 4/3/2007). Earlier this year the company introduced oncology testing for a limited number of indications just before it was bought by PerkinElmer for $90 million in April (BAN 4/20/2010).
Signature's cancer testing services are performed on its OncoChip array, a Roche NimbleGen-manufactured, 350,000-probe CGH microarray that it is analyzed using the firm's internally developed Oncoglyphix software.
In February, Signature rolled out testing services for chronic lymphocytic leukemia and myelodysplastic syndromes. In May, the company began marketing OncoChip for chronic myeloid leukemia and myeloproliferative disorders. Shaffer said the firm will launch services for acute lymphocytic leukemia this month. A lymphoma offering is expected later this summer, and other undisclosed indications are in the firm's pipeline.
"We are rolling them out in stages," Shaffer said. While all tests run on the same OncoChip design, Signature validates the applicability of its diagnostic before making it available as a service. "We want to do at least 30 cases of each disease before we roll out the service, so it’s taking us time to validate each disease," she said.
Oncology is a new market for Signature, which last year posted $20 million in sales derived from its postnatal and prenatal testing services. Shaffer said that currently in the US, based on the number of births, there are about 120,000 babies born with a birth defect or some sort of genetic problem that should have a chromosome analysis, while about 3 percent of the population has mental retardation, a segment the firm considers the legacy market.
Signature addressed the prenatal market "because there are 400,000 karyotypes done annually," making it "four times the postnatal market," leading the company to believe that the "community is better served on microarrays."
According to Shaffer, the oncology tests Signature has on the market and others slated for launch address a similar market size.
"For just the hematological malignancies, the leukemias and lymphomas, there are 375,000 new tests done each year to rule out those diseases" in the US, she said. "It’s again three or four times the postnatal market."
According to the Leukemia and Lymphoma Society, approximately 140,000 people are diagnosed with leukemia or lymphomia in the US annually. BioArray News could not independently verify how many tests are used to diagnose those diseases.
As with the constitutional abnormality-testing segment, Signature hopes that its use of arrays will allow it to capture money currently spent on services that rely on traditional cytogenetic methods like fluorescence in situ hybridization and karyotyping, Shaffer said. "Cancer chromosomes are short, and the worst looking ones are the ones that usually carry the abnormalities," she said. "The whole purpose of using the OncoChip is that I know that with microarrays we can do a better job.
"Will we replace chromosomes and FISH for every disease? The answer is probably no," Shaffer continued.
She said that for some diseases arrays will be a replacement and for other diseases it may become an adjunct technology. "In certain instances, such as when you have a hyper diploid, it will be very hard to detect abnormalities on an array because there are so many things going on and the arrays just look noisy," she said.
"It will take us sometime to figure out, and for the key opinion leaders to develop protocols on how they should be used, but you can’t make those decisions until you have done some samples and you demonstrate the value of this test," she added.
In the future, Shaffer speculated, there will be organizations like the nonprofit Children's Oncology Group that will develop protocols that will likely include microarrays.
In addition to classical cytogenetics, Signature will also face competition from other array-based testing services like Irvine, Calif.-based CombiMatrix Molecular Diagnostics, which markets its suite of HemaScan tests for the management of hematological malignancies.
One capability Signature is touting is its ability to detect balanced translocations in cancer samples. Balanced translocation, a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes, is a condition that has been so far been undetectable using CGH as CGH only measures gains and losses, the difference between a "normal" genome and an "abnormal" genome.
However, unlike using a whole-genome scan to detect constitutional abnormalities, where it has been impossible to date to determine which parts of the genome differ from the normal for lack of telltale duplications or deletions, many common areas of translocations in cancer genomes have been identified. This has allowed Signature to use an internally developed technique to identify their presence in case samples.
"We have launched services for CML, and the hallmark feature of CML is the 9;22 translocation, which is one of the translocations we can detect," said Shaffer. "Balanced translocations tend to be disease specific."
Identifying a balanced translocation is "technically very challenging," and Shaffer believes Signature's ability to do so could give it an advantage over rivals. "I don’t think anyone can reproduce this technology easily," she said.
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Beyond oncology, Signature is also moving into the so-called neuropsychiatric market. Shaffer said that the number of loci recently identified for autism, schizophrenia, bipolar disorder, and other conditions have already been included on the company's 135K whole-genome SignatureChip, and that making the service available to physicians will require more market outreach than product development.
"Most of these loci are already on our postnatal SignatureChip, the 135K, but we can target the younger adult and older adult populations, which is something Signature historically hasn’t done," Shaffer said of the market. "It's really more of an education of the physicians to make them more aware that these disorders can be caused by genomic gains and losses," she said.
Again, CombiMatrix will be a competitor. The firm sells a test called ATScan for the diagnosis of autism spectrum disorder. Other companies with interest in the space include France's ExonHit Therapeutics and Norway's DiaGenic, both of which have developed tests for early-stage Alzheimer's disease diagnosis.
Shaffer said the availability of genetic testing for such diseases is "important because, I think, traditionally the psychiatrists treated the problems based on the clinical presentations." Now, she said, " in some of these individuals you can find a genomic disorder, which gives families information they can use.
"It’s a learning process, an education of the physicians, so that they know these things are available to them," she added.
While Signature plugs away with new product development programs, it is slowly being integrated into PerkinElmer, which closed its acquisition of the firm on May 17. Shaffer said that Signature agreed to the business combination because it was the "perfect strategic move" for the company at the time.
"We really got to the level that a lot of startups get to," Shaffer said. "At the time we were 120 employees doing $20 million in revenue and we were seeing our volumes plateauing while we [had] previously enjoyed very steep growth year over year," she said. "And so it was time to do something different — to either hire more sales [people], or to participate in some type of strategic acquisition. Last fall, PerkinElmer came to us, and it seemed like the perfect strategic move for Signature."
Waltham, Mass.-based PerkinElmer said it would retain Signature's operations in Spokane and has even begun moving some of its testing there over the past month, according to Shaffer. PerkinElmer also appointed an "integration lead" to oversee the alignment of the two firms' financial systems and coordinate their sales and marketing activities.
"PerkinElmer is talking to our various departments to get us aligned, because this is permanent," Shaffer said. "We can’t just be our own entity, a little island."
Shaffer estimated that integration into PerkinElmer will take about a year. "This is a huge company; we are little," she explained. Signature currently has 115 employees, while PerkinElmer employs about 8,800 people.
One outcome of the acquisition will be Signature's development of a product offering based on PerkinElmer’s BACs-on-Beads technology, which is based on bacterial artificial chromosome technology it acquired when it bought Houston, Tex.-based Spectral Genomics in 2006 (BAN 10/10/2006). The platform relies on BACs immobilized onto Luminex encoded beads that are used to assay chromosomal gains and losses from samples in 96-well plates.
Shaffer said that though the company provides targeted genome scans in addition to its whole-genome scans for prenatal cases, some physicians still view its targeted array, the SignatureChipTE, as too high resolution for their needs.
The BACs-on-Beads assay appeals to such physicians because it sits between FISH and the SignatureChipTE in terms of resolution, Shaffer said.
"What we picked for our BACs-on-Beads assay are those microdeletion disorders that don’t have abnormal ultrasound findings because if you have the abnormal ultrasound, you should probably go for the array," Shaffer said. "We hope it will give our physicians more choices." Signature hopes to launch its BACs on Beads assay by the end of this year.