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Korean Startup 3billion Focuses on Rare Disease Community With DTC Exome Screening Test

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NEW YORK (GenomeWeb) – Korean startup 3billion is getting ready to offer a direct-to-consumer genomic rare disease screening test to patients in the US who are looking for a molecular diagnosis and haven't been able to obtain one otherwise.

The company, a spinoff from Korean genomic services provider Macrogen, said last week that it has begun testing its service in a closed beta program involving 100 patients who will receive exome sequencing and annotations of variants linked to more than 4,000 rare diseases.

3billion, which currently has four employees and is located in a venture incubator in Seoul, was founded last November by three former Macrogen employees — CEO Changwon Keum, a bioinformatician who previously designed clinical genome tests for Macrogen; DH Park, a biochemical engineer and former NGS sales manager at Macrogen; and Sehwan Kim, a bioinformatician and former senior researcher at Macrogen — with about $300,000 in seed funding from the parent company and a small amount of funding from Digital Healthcare Partners, which advises the company.

The firm is hoping to raise approximately $5 million later this year from venture capital firms and other investors in a Series A funding round.

Park said in an interview that he and his colleagues noticed that many rare disease patients are having a hard time obtaining a molecular diagnosis, either because their health insurance does not cover genomic testing and they can't afford to pay for it out of pocket, or because they cannot get into research studies that would pay for the testing. This includes patients who already have a clinical diagnosis, he said, but who still want to obtain a molecular diagnosis in order to find out about the genetic origin of their disease. 

"They have this desire to know more about their conditions but they don't have access to the sequencing technology," Park said.

For those patients, 3billion plans to offer a less expensive alternative. While the company has not yet finalized pricing, Park said that the exome sequencing screening test it plans to roll out first will cost less than $1,000.

Starting in May, 3billion plans to launch an open beta testing program, for which patients can currently sign up on its website. Patients are asked to provide their email address, a short description of their symptoms, and, if available, any conditions they have been diagnosed with.

Customers will receive a saliva collection kit in the mail and return their samples to an undisclosed US-based CLIA laboratory that 3billion has partnered with. The lab will sequence their exome to 100x depth, according to 3billion's website, and the company will analyze the data for pathogenic variants associated with more than 4,000 rare genetic diseases, based on databases such as ClinVar and using guidelines for variant reporting by the American College of Medical Genetics and Genomics. Approximately eight weeks after 3billion receives their sample, customers can explore the results – annotated rare disease variants along with published information about them – on the company's website. In order to maintain customers' privacy, 3billion uses HIPAA-compliant cloud storage for their sequencing data.

In addition, customers will be able to download their raw sequence data in FASTQ format and their variant data as a VCF file, which they can share with their geneticist or submit to third-party interpretation services. 3billion will also provide them with a printable PDF report that they can share with their doctor.

For its closed beta test, which is free of charge for the 100 participating patients in exchange for their feedback, 3billion reached out to rare disease patient advocacy groups in the US, including the Rare and Undiagnosed Network (RUN), which is working towards bringing genome sequencing for undiagnosed patients into clinical practice. The company also contacted individual patients running blogs on rare or chronic diseases to recruit beta testers.

Interest in the service by far exceeded the 100 patients the company was looking for, Park said, and it selected participants for its closed beta test based on certain conditions it was interested in, though it also included a number of undiagnosed patients. The company plans to publish the results of the study in a peer-reviewed journal. It also intends to follow up with patients to find out how they will use the information.

"A lot of them will probably take it to their healthcare professionals, or use other online platforms," Park said. "Getting that feedback will be important for us to position ourselves, and to find out what kind of data and results we provide to patients so they can move on to the next step in the [diagnostic] process."

Park said 3billion cannot offer its service in Korea due to that country's strict regulations on DTC genetic testing, which he said prohibits companies from providing anything other than raw sequencing data to individuals.

The company believes that regulations in the US are less rigorous, which is why it is currently focusing on the US market. While any interpretation of sequence data for diagnostic purposes requires a prescription from a healthcare professional and a CLIA-certified lab, Park said, 3billion believes that this is not the case if variants are merely annotated with information from databases and the scientific literature. "We are not making the interpretation, we are only providing information related to the annotated variants," he said.

On its website, 3billion states that its screening service is not a medical test. "We do not provide any preventative, diagnostic, or clinical information. We provide a digital platform for you to explore your genome. 3billion services are for research, information, and educational use only," according to the website.

It remains to be seen, though, whether the US Food and Drug Administration agrees with this assessment. Up until now, the agency, in its regulation of healthcare-related genetic tests, has only allowed carrier screening tests to be sold without a prescription from a doctor. It has also stated in the past that it intends to regulate direct-to-consumer genomic testing.

Last September, for example, the FDA sent a letter to Tute Genomics, which had planned to offer whole-genome or exome sequencing to consumers, including reports on actionable variants and disease risks. As a result, Tute, which has since been acquired by PierianDx, suspended its Kickstarter fundraising campaign.

Also, a year ago, the FDA sent a letter to Sure Genomics, asking why it was marketing its SureDNA sequencing test without the agency's clearance. Sure Genomics had launched a DTC whole-genome sequencing test and had planned to offer customers reports on disease risks, drug response, health and wellness, traits, and ancestry.

Other exome and genome sequencing and interpretation services that can be ordered directly by consumers, such as those from Genos and Veritas Genomics, require an order from a physician.

Longer term, 3billion hopes that the database of rare disease patient data it plans to build will lead to new discoveries of disease mechanisms and treatments. "We believe that through our service, we will be one of the first in the world to have an extensive database dedicated just to rare diseases," Park said. "We plan on sharing our results with researchers in hopes to discover new causal variants or treatment methods."