NEW YORK – As next-generation sequencing has become a routine tool for disease diagnostics, Swiss clinical product manufacturer 4bases is hoping to expand its DNA sequencing test offerings to capture more of the global market.
The Manno-based company, which focuses on producing NGS-based diagnostic kits, recently struck a partnership with Oxford Nanopore Technologies to develop test products for BRCA1 and BRCA2 breast and ovarian cancer susceptibility genes. The firm is also looking to scale up its diagnostic panel tests to include more genes as the cost of sequencing continues to go down.
According to 4bases Cofounder and Chief Operating Officer Fabio Grandi, the company's collaboration with Oxford Nanopore officially kicked off a few months ago, but the conversation between the two firms started last year.
In this partnership, 4bases will develop and validate its own products, adapting them to Oxford Nanopore's sequencing workflow. The first kit to be released is a rapid test for BRCA1 and BRCA2, which promises a same-day turnaround for the entire protocol. In addition, Grandi said the company is currently validating other products for nanopore sequencing, including a CFTR gene analysis kit for cystic fibrosis.
The company's existing distribution network in the clinical diagnostic market enables it to offer nanopore sequencing-based kits to its customers in Italy and Switzerland, Grandi said. Compared with short-read sequencing approaches, which the company's kits are previously built upon, long-read sequencing can open the door to directly analyzing large genetic variants, promising an "enormous step forward" for the diagnostic field, he added.
Founded in Italy in 2013, 4bases currently produces roughly two dozen CE-IVD marked NGS kits for genetic diagnostics, marketed to clinical labs, hospitals, and healthcare providers to run these tests on their own sequencers. Soon after the company's inception, Grandi noted, it moved its headquarters to Switzerland while maintaining its production facility in Italy.
According to Grandi, 4bases' products largely fall within two categories: amplicon-based panel assays or capture-based tests using probes. While the amplicon-based kits are designed to target a few specific genes, capture-based products are geared toward applications that typically involve a larger number of gene targets. In terms of disease areas, Grandi said the company's tests cover both oncology and genetic disorders.
Besides these, 4bases has also launched whole-exome and clinical exome tests. Grandi said the company's clinical exome kit, which includes more than 10,000 clinically significant genes from the Online Mendelian Inheritance in Man (OMIM) database and is updated every six months, is validated for germline analysis of variants such as single nucleotide polymorphisms (SNPs), indels, and copy number variations (CNV).
Grandi said 4bases is not producing the raw ingredients of its kits in-house. Instead, the company has reached agreements with manufacturers around the world for supplying the materials, such as probes or enzymes, and 4bases assembles these components into kits that are then validated for clinical use.
Downstream, the company has also developed proprietary software to help analyze data generated by its kits at scale. Dubbed 4eVar, Grandi said the software, which also has obtained CE-marking for diagnostic use, can help prioritize genetic variants detected in the tests based on the relevant phenotype.
That said, Grandi noted that a significant portion of the company's IP portfolio pertains to the machine learning-based data-analysis approach developed for its kits.
Most of 4bases' kits are optimized for Illumina sequencers, with a fraction also validated for Thermo Fisher Scientific's Ion Torrent platform. Grandi said the company's products are fundamentally compatible with any sequencers, though, with the initial library prep process being identical.
Currently, 4bases sells its products through local distributors, Grandi said. While its main market in Europe is Italy, he said the company has also garnered an increasing number of customers in diagnostic clinical labs in countries outside of Europe, such as Egypt, Morocco, India, and Pakistan, as well as those in South America. The company's tests are available in 70 countries, which does not include the US, according to Grandi.
Grandi did not disclose specific pricing for the company's kits but said that it believes it has a competitive edge in this area. "We generally do not have a very expensive portfolio," he claimed. "We can be competitive because we are [our own] producer."
Other European companies, such as Swedish diagnostic company Devyser, also produce NGS-based diagnostic assays. To that, Grandi said while 4bases faces competition from Devyser in some gene applications, such as BRCA1 and 2 or CFTR, the latter currently does not offer solutions for clinical exome.
As NGS becomes more and more accessible, Grandi said 4bases is also working to scale up its offering to include more genes in one test. "The sequencing cost is drawing down, and the number of samples that can be analyzed at the same time is going up," he said. "We are more and more convinced that the larger [tests] like clinical exome and whole exome will be the focus in the near future."
Grandi said 4bases is entirely funded by its shareholders and does not intend to raise additional capital in the near future. In addition, he said the government of the Canton of Ticino, through its financial institution, was also one of the first partners and financiers of 4bases and remains as the company's minority shareholder.
Grandi said the company is also looking to expand its product roadmap to cover applications outside of human disease, such as microbiology, veterinary, and agronomy. The company currently has around 20 full-time employees and is planning to expand its workforce within the next year, he added.