NEW YORK – As large-scale research projects exploring genome sequencing for newborn screening are getting underway worldwide, a number of companies are starting to offer genomic testing for newborns and children as a commercial service directly to families.
Among the latest entries is Fore Genomics, a San Diego-based startup that recently launched its first product, a genetic testing service called Foresite 360 that targets parents of seemingly healthy children who want to learn more about their offsprings' predisposition to genetic disorders.
"Our goal is to understand genetic disease early in life, so we can put in place clinical management plans and help families, help doctors, treat disease as early as possible," said Matthew Pelo, Fore Genomics' founder and CEO. Prior to founding the company in 2020, Pelo led finance operations and business development at the New York Genome Center for almost a decade.
For just under $3,000, Fore Genomics analyzes DNA from a child's saliva sample by whole-genome sequencing, looking for genetic variants associated with more than 300 diseases that can be treated or managed, as well as pharmacogenetic variants linked to 40 medication types. In addition, parents obtain annual updates on genetic health risks until their child turns 18.
"Everything we test for presents in the first or second decade of life," Pelo explained, so no variants for adult-onset conditions, such as those in BRCA genes, are included. He expects that most parents who will order the test have kids under the age of 5. "There's more benefit the earlier you take it," he said.
Parents can order Foresite 360 online directly from the company, which works with doctors who prescribe the test. A saliva sample collected at home is then sent for whole-genome sequencing to one of several CLIA-certified and CAP-accredited clinical labs that the firm has contracted with. While Fore Genomics previously worked with the HudsonAlpha Clinical Services Lab, it switched to two currently unnamed labs over the summer, Pelo said. Sequencing is done on Illumina systems with a mean coverage of 40X. The test is available in all US states and has a turnaround time of six to eight weeks, according to the firm's website.
The sequencing data are analyzed and interpreted through "our own in-house analysis solution," Pelo said, which has been developed internally as well as through partnerships. According to the firm's website, it uses the Illumina DRAGEN Bio-IT platform for primary data and tandem repeat analysis. For secondary and tertiary analysis, it uses ODIN software for SNVs and Biodiscovery's NxClinical or Illumina's DRAGEN Bio-IT platform for CNVs and to determine the absence of heterozygosity (AOH). To screen for spinal muscular atrophy and repeat expansion disorders, in-house bioinformatics tools are used "based on the published literature with modification," the website states.
Parents obtain a clinical report informing them about disease-related variants and the associated conditions. No variants of uncertain significance are included. The report also contains resources, such as disease foundations or expert physicians, so parents know who to turn to with positive results. Fore Genomics also offers pre- and post-test genetic counseling through a partnership with GeneMatters, a Genome Medical company, including for a child's physician.
"Our goal is to make the information usable clinically," Pelo said. "So you're not stopping with 'Here, parent, is your clinical report; now you figure out what to do with it.' We want to see it all the way through and even work with the child's doctor to implement clinical management plans."
For data storage and reanalysis, Fore Genomics uses DNAnexus, which provides a cloud-based platform that Pelo said is a "best-in-class solution" in terms of data privacy and security, offering HIPAA-compliant, US-based storage.
Parents currently don't have a choice which diseases they do or don't want to learn about, and the number of genes and conditions reported keeps changing as new studies come out. "Right now, it's 'one-size-fits-all,'" Pelo said, because a customized version would be "not that easy to do."
As a child grows older, more conditions are included in the annual updated report. "When I talk to parents, what they're interested in when a child is 0 to 2 is very different than what they're asking about in a child 5 to 10 … so we've designed our screen to expand as the child grows," Pelo said.
Since Foresite 360 is considered a lab-developed test, he said, the company has not yet engaged with the US Food and Drug Administration, but it is aware of the FDA's ongoing efforts to start regulating LDTs and is "watching that closely."
According to Matthew Bainbridge, associate director for clinical genomics research at Rady Children's Institute for Genomic Medicine, one of the biggest challenges for companies like Fore Genomics will be "explaining to parents the value that having their child's genome provides. For critical diseases in the first years of life, and again when they are teenagers, and with more common diseases and conditions as they get older. It's really an investment in your child's future."
Compared to current newborn screening, genetic screening tests like Foresite 360 look for more conditions and can sometimes even resolve false-positive results from newborn screening, he said. As CEO of Codified Genomics, which provides clinical genomic variant interpretation to researchers, Bainbridge is an adviser to Fore Genomics.
Pelo said the company has seen "quite a bit of interest" for Foresite 360 and has already returned results to parents, though it doesn't disclose testing volumes. "One of our challenges is that people don't know this type of test exists," he said, though parents are often "pretty knowledgeable about genetics" as many have already undergone carrier screening, noninvasive prenatal testing, or, if they opted for in vitro fertilization, preimplantation genetic screening.
Fore Genomics is not the first company to offer genetic screening of children based on whole-genome sequencing. ViaCord, a subsidiary of Revvity, for example, has been providing genomic testing for newborns and children since 2017. Its $2,500 whole-genome sequencing test, for example, analyzes 2,500 genes known to be associated with childhood-onset conditions. Earlier this year, ViaCord published a study that compared results from almost 600 newborns and children undergoing genome sequencing with those of more than 600 having panel sequencing. It found that the whole-genome sequencing uncovered four times as many potential pediatric-onset diagnoses than more limited sequencing, in about 8 percent of apparently healthy children. Almost half the findings were associated with high-penetrance conditions.
Another startup, Nurture Genomics, founded by Robert Green, co-PI of the BabySeq study and a professor of medicine at Harvard Medical School, is about to launch. According to its website, it will provide "newborn genetic screening with ongoing personalized support to deliver genomic-guided care." Green said that rather than a lab, Nurture will be "a medical practice and navigation system for genomics-guided care."
Pelo said he would be happy to work with ViaCord, Nurture, and others to develop standards for genetic newborn screening, such as what genes to include in the test. "Everyone's kind of come up with their own screening list," he said. "We all use the same criteria with different genes. So it would be nice to work together on 'what are the best practices here, what should we be doing?'"
While Fore Genomics has "raised some money" already, he said, it is in the midst of closing a multimillion-dollar seed/Series A financing round to expand its commercial activities. At the moment, the company has 13 employees, some of them working part-time.
Going forward, the company would like to study whether genetic screening in children leads to better outcomes later in life. "No formal study has started, but we've built our systems to collect data and understand implications of predisposition testing," Pelo explained. "Our goal is to understand the pros and cons for predisposition testing in more detail, similar to other studies currently in process."
The firm is also interested in working with pharmaceutical companies that are developing new treatments for genetic diseases. "We've had multiple conversations with pharma companies, mostly focused on rare disease," Pelo said. "Our conversations are not discovery-stage but focused on making sure parents and doctors have all available information when receiving a predisposition diagnosis, including commercial and clinical-stage therapies. It is ultimately up to the doctor and family to decide on correct treatment plans, though."
Fore Genomics also sees future opportunities for expanding its test by including RNA sequencing or epigenetic analyses. There is currently no firm timeline for this, but the goal is to launch the next test in mid-2024.
It remains to be seen how many parents will decide to use the company's service for their healthy children, given that many have reservations about genetic privacy and possible future genetic discrimination, despite federal laws such as the Genetic Information Nondisclosure Act (GINA). However, Pelo said he believes many parents want to be proactive when it comes to potential future diseases of their children. "There's a lot of interest in this," he said. "When you're out talking to parents, everyone's got a relative, a neighbor, you name it, that has experience with some undiagnosed disease or rare disease diagnostic odyssey."