NEW YORK – Dante Labs is working with the Italian government to introduce a clinical whole-genome sequencing screening test into the Italian healthcare system, with the goal to make the offering a component of routine clinical care.
According to Dante Labs CEO Andrea Riposati, the Italian Ministry of Economic Development has committed €8 million ($8.4 million) to the project, following a government call for high-impact innovations in healthcare and life sciences as well as projects that could have an impact at both the national and EU level. "We responded and won," he said.
The company, based in L'Aquila, northeast of Rome, currently offers a whole-genome sequencing service called the Dante Whole Genome Test, which for €550 promises customers a wide range of information related to prevention, nutrition, fitness, and predispositions to more than 80 diseases and conditions, as well as genetic counseling. The test obtained a CE-IVD mark in 2020, and Dante announced an update for the assay, which sequences the genome at 30X coverage and relies on the firm's Extensa software for reporting and interpretation, in March.
For its new government-backed project, Dante Labs will create an offering called the Dante Citizen Test. Riposati described the test as a custom version of the Whole Genome Test, "leveraging our Dante Platform, our bioinformatics and software capabilities, and, in general, our experience sequencing tens of thousands of genomes on multiple sequencing platforms."
Riposati said that Dante Labs has arrived at the realization that healthcare systems and patients need something more than the standard whole-genome sequencing at 30X and that the company, given its experience, could offer something different that is also reimbursable within a healthcare system. They have opted for what he called a hybrid approach, where short-read whole-genome sequencing at 30X plus a custom long-read panel will be employed.
"The long-read panel will be manufactured to maximize the benefits of the long reads while keeping implementation simple and costs down," commented Riposati. "The full sequencing pipeline will be reproducible also by other genomic laboratories."
Indications targeted will depend on medical history and age, said Riposati. Newborns would not receive information related to Alzheimer's disease, he said, while healthy adults would not receive reports on pediatric diseases. People with specific medical conditions would receive tailored reports relevant to them.
According to Riposati, the firm will rely on a multi-platform approach to carry out the sequencing, though he did not elaborate.
Riposati, a former senior product manager at Amazon who helped launch the Amazon 3D Print Store and Amazon B2B Marketplace, cofounded Dante Labs in 2016 with CSO Mattia Capulli. The two knew each other from high school and reconnected in New York, where Capulli was doing a postdoc in biotechnology at Columbia University. They decided to set up the company in New York and in L'Aquila, a medieval Italian town with a university that specializes in life sciences, computer science, and physics.
"It's also close to Ciampino Airport, which is DHL's primary hub in Italy, so it is very convenient to receive samples from all over the world," remarked Riposati. "Logistics is important for me, given my Amazon experience."
The past few years have been eventful for the firm. In June 2020, Dante Labs announced a partnership with Cambridge Cancer Genomics and Nonacus, both based in the UK, to develop a high-throughput cancer sequencing and interpretation service. A year later, Dante Labs acquired Cambridge Cancer Genomics for an undisclosed sum. Earlier this year, Dante Labs formed a drug development alliance with the Renato Dulbecco Foundation in the area of cancer, COVID-19, and rare diseases. In April, the firm announced a partnership with the Abu Dhabi Stem Cells Center around genetic testing and vaccine development.
According to Riposati, Dante Labs maintains R&D operations in Italy, including a clinical sequencing laboratory, and has a similar lab in the United Arab Emirates. Dante Labs also has offices in the UK and now in Menlo Park, California, to where it relocated from New York.
The new project with the Italian government thus follows a flurry of activity and reorganization within the firm. It is also being overseen by a newly appointed European medical genomics board within Dante Labs, which Riposati said consists of specialists in genomics and experts in prenatal and neonatal testing as well as pediatric rare diseases.
Riposati did not name any members of the board but said that accomplishing the integration of genomics and healthcare requires a "local approach, because of ancestries and different regulatory environments," and cited differences between the US, Europe, and the Middle East, where Dante Labs is active.
"A medical genomics board enriches our experience and enables Dante to provide the best clinical genomic insights by leveraging the best people in the fields," said Riposati. "The board is diverse," he added, "with individuals with multi-year experience in different areas."
Dante Labs is also liaising with Giuseppe Novelli, whom Riposati described as a "key opinion leader," on its project to introduce the Dante Citizen Test into the Italian healthcare system. Novelli is a professor at the University of Rome Tor Vergata, where he is also head of the human genetics research unit.
Novelli said in an email that he is familiar with the Dante Labs project, characterizing it as "important" in improving the diagnostic yield and impact of sequencing. According to Novelli, while whole-exome sequencing and whole-genome sequencing are the most used methods to identify pathogenic variants, diagnostic rates remain suboptimal, and only between 30 and 60 percent of patients sequenced receive a diagnosis.
"This is partly due to the fact that NGS-based diagnostic tests are limited to known disease genes," said Novelli, adding that a large number of human genes have no known biological function yet, and their role in human disease has yet to be discovered. Additionally, many functional variants with a possible phenotypic effect reside outside the coding regions, Novelli said.
According to Novelli, by both sequencing and delivering back reports to patients, the Dante Citizen Test could help to drive new discoveries and, eventually, improve diagnostic yield over time.
"Exploring, deepening, and above all validating and qualifying, according to international rules, new genomic protocols could be of great help in the future of public health genomics," said Novelli.
Italy, he underscored, is just one of many countries that are looking to bring omics into the clinic. As such, it is imperative that countries evaluate and experiment with genomic technologies, such as whole-genome and whole-exome sequencing. By evaluating new approaches and tools methodically, clinicians can avoid making mistakes, while making such approaches available in a uniform way throughout the country.
"My laboratory, together with other Italian laboratories competent on these issues, will be able to provide the necessary support to validate technologies and protocols developed by companies to achieve this goal," said Novelli. Such assistance includes interpretation of variants of uncertain significance, as well as to carry out functional studies of such variants.
Novelli noted that his lab and Dante Labs have cooperated on these issues since reaching a scientific collaboration agreement last year.
According to Riposati, Dante Labs is eager to drive adoption of whole-genome sequencing in clinical care in Italy because the company believes the value of the technology is not yet impacting average citizens. He said that even though the cost of sequencing a whole genome dropped below $1,000 several years ago, obtaining actionable information from the raw data, and making the technology widely accessible, has constrained its adoption in the clinic.
"Our focus has always been on extracting actionable, clinically relevant insights from genomic data, so that we can provide the full benefits of WGS to individuals and their doctors," said Riposati.
"Raw data is great," he went on, "but most patients and clinical professionals don't have the tools to analyze raw data, nor should they be spending their precious time analyzing raw data." He maintained that Dante Labs has the tools in hand to support patients and clinicians.
In terms of rolling out the test, he noted that the Italian healthcare system is both centralized and decentralized, and therefore introducing the Dante Citizen Test will follow a double approach of liaising with the Italian Ministry of Health, which oversees the Servizio Sanitario Nazionale, or National Health Service, in parallel with regional health authorities, which administer services at the local level.
According to Riposati, Dante Labs has already signed the first hospitals to "create successful case studies for a rapid national rollout" of the Dante Citizen Test, though he did not elaborate on the scope of the studies. Two other hospitals that are collaborating are Ospedale Pediatrico Bambino Gesù and Ospedale Tor Vergata, both located in Rome.
He noted that the test is being designed to be fully reimbursable. Dante's proposed reimbursement categories are newborns, rare disease patients, people with a family history of a life-threatening disease, and people undergoing a treatment or surgery who would benefit from whole-genome sequencing. Actual coverage, he noted, will depend on negotiations with national and regional governments. Ideally, Riposati said, the Dante Citizen Test will become available to all Italians.
"My personal view is that everyone deserves to have his or her whole genome sequenced for free and that access to the whole genome should be a human right," said Riposati. "Hopefully, we will achieve this goal in a few years."