NEW YORK – Dutch genomics company Cergentis and partners recently completed an analytical validation study of its targeted locus amplification, or TLA, technology in lymphoma, showcasing its ability to detect clinically relevant translocations in tumor biopsies that are formalin-fixed and paraffin-embedded.
The work, featured in Nature Communications last month, involved researchers from the Hubrecht Institute in Utrecht, as well as lymphoma experts from five Dutch pathology laboratories and was the culmination of years of work by Cergentis and its users. Cergentis had initially employed its TLA approach in liquid biopsies to study blood cancers, such as leukemia, but had sought to hone the method for use in solid tumors.
The company is now seeking a partner to commercialize the technology for oncology in a kit format while it continues to grow its service business for the biopharmaceutical industry.
"For us, it's an important building block for when we reach out to potential partners," said CEO Joris Schuurmans of the new study. "We now have something robust in the public domain as a collaborative product between ourselves and clinical and academic collaborators."
Cergentis' TLA technology fits into a targeted next-generation sequencing workflow and can be tailored to detect clinically relevant variants for diagnostic purposes. The approach works by cross-linking DNA that is close to a gene or region of interest. The DNA is then digested with a frequently cutting restriction enzyme, and the fragments are ligated into large circles.
After removing the cross-links, the DNA is converted into smaller circles, and circles containing the gene of interest are subsequently amplified with PCR. The amplification products are sequenced, and target sequences are subsequently reconstructed from the reads using Cergentis' PLIER algorithm.
When coupled with standard target enrichment and next-generation sequencing methods, Cergentis claims that its approach allows users to detect variation at a greater scale than conventional techniques.
The company sees the approach as an alternative to fluorescence in situ hybridization, which is used widely for detecting translocations in lymphoma. Daphne de Jong, hematopathologist at Amsterdam University Medical Center and a coauthor on the Nature Communications paper, referred to Cergentis' TLA approach as the "hoped-for alternative for cumbersome FISH analyses."
"The value of TLA is that we can provide very comprehensive genomic analyses of the locus of interest," Schuurmans noted. Schuurmans became CEO of the Utrecht-based 9-year-old company last year. In his words, it was part of the "natural maturing of the company as part of the commercial, industrial phase of its lifecycle."
Prior to joining Cergentis, Schuurmans managed the melanoma program at SkylineDx, a Rotterdam-based diagnostics company that has developed a number of array and sequencing-based tests. He also was CEO at MyCartis, an immunodiagnostics provider.
Schuurmans' arrival to Cergentis coincided with a strategic reassessment of the company's trajectory. Much of its work in oncology was supported through a €1.2 million ($1.4 million) EU Horizon 2020 grant to develop its TLA technology for target locus capture, or TLC, in FFPE tumor biopsies.
According to Schuurmans, the oncology work featured in the study however has reached its end, along with the Horizon 2020 grant. "That oncology program is now finished," said Schuurmans. "The publication showcases the application of our technology suite in the space of oncology."
A fundamental choice
Cergentis believes that a kitted version of its FFPE-TLC technology could be made available to users, but would prefer a partner to take over the business of manufacturing, distributing, and supporting it. This is because the company under Schuurmans has decided to focus its energies on its services business instead.
"Over the past year, we made a fundamental choice to focus on the biopharmaceutical side of our business," he said. The company has built a customer portfolio around applications centered on its TLA technology. This is offered not only to biopharmas, but to academics too. It involves the provision of comprehensive genomic analysis services, clonality assessments, and genetic stability assessments. The firm also offers transgene integration integrity assessments for biopharmaceutical producer cell lines, and works with transgenic animal models, and cell and gene therapy products.
This versatility in services underlies a shift away from the idea of becoming a provider of TLA kits or a foray into molecular diagnostics. "Obviously if you want to develop yourself as a mature and competent player in that space offering robust services to the biopharmaceutical industry, there is a set of capabilities that you have developed that are completely different than if you develop and sell cancer diagnostic products," noted Schuurmans. "Of those two potential avenues for the company, we had to pick one and we decided to focus on the biopharmaceutical industry."
The decision appears to be paying off. Schuurmans said the firm has already established a "nice track record" in the space, with 50 publications or so in the public domain related to its work and 2,000-plus projects completed for pharma customers. There is also the matter of "strong revenue growth," hard to quantify for a privately held firm but sizable enough that the company is not seeking additional funding at the moment following a private placement reported last year.
The customer mix is international: Slightly less than half of Cergentis' clients are in the US, and the remainder are European, with the Netherlands leading the pack. There is room for expansion though, notably to the east. "The white space for us on the map is the biosimilars industry in India, and the People's Republic of China's biopharma industry is as large as the one in the US," noted Schuurmans. Opportunities abound in Japan, South Korea, and Taiwan, too.
Most of Cergentis' clients are not big pharma, Schuurmans noted, but rather mid-cap or smaller pharmas, out to get into the clinic. "They don't have the patience or need to develop the infrastructure in house to perform comprehensive genomic analysis by doing their own sequencing," said Schuurmans. "Outsourcing for this market is a very dominant trend," he added. Many customers are contract research organizations and contract manufacturing organizations.
A true opportunity
Cergentis also recently announced its membership in the US National Institute of Standards and Technology Genome Editing Consortium. The consortium, established several years ago, aims to evaluate genome editing assay pipelines, develop benchmark materials, and generate benchmark data. It also aims to develop minimal information reporting standards for public studies and to craft a lexicon for genome editing studies. Current members include Agilent, AstraZeneca. Illumina, Lonza, and Thermo Fisher Scientific, among others.
Schuurmans sees Cergentis' consortium membership as a "true opportunity" for the company. "We definitely want to be part of the cohort of companies that together with regulators and key opinion leaders define analytical standards for genome editing," he stated. Schuurmans noted that the technology mix and analytical standards for cell and gene therapy remain in flux, and the business continues to grow. Fitting its offerings into analytical standards could benefit the firm.
In particular, Cergentis believes it could provide identity assays for gene therapy products, offering quality control of clinical batches as part of regulatory oversight. As such, the firm continues to invest in its customer experience, including building out a customer portal to support onboarding new clients and allowing them to manage their projects and interact with scientific account managers.
The company is also investing in its quality management system and plans an upgrade for later this year. There are also plans to enable customers to implement TLA within their own workflows, which means the firm isn't entirely getting out of the kit business. The company plans to soon offer assays for CHO clone selection.
"In the process of cell line development, multiple clones are developed," noted Schuurmans. "Our first assay can help customers select the right clone to proceed with cell banking."