Yoshiyuki Sakuraba, Ph.D., CEO and Yoko Nagai, Ph.D., CTO
If there was one thing that Yoshiyuki Sakuraba remembers from his days as an executive clinical sales specialist at Illumina, the DNA sequencing giant, it was the fact that every day came as a moment of realization and inspiration for breaking the status quo of Japan’s genomics sector, which was at an embryonic stage. “With the zeal to develop clinical applications for the Japanese market, I used to visit many companies, including some of the largest clinical testing firms and even small bio-ventures, and work with them on the latest technologies. Surprisingly, no one had started genomic applications, probably because Japanese businesses were conservative,” he says. Sakuraba, however, was not the only one to realize the missed opportunities. Yoko Nagai, his colleague at Illumina, was equally disappointed at the state of genomics in her country. The duo felt that Japan was falling behind in the quickly advancing global genomics testing scene.
“Most of our discussions revolved around how to disrupt the status quo and lay the foundations for a flourishing genome market,” mentions Sakuraba. And it was no later that a promising proposition emerged from this deliberation—“What if we establish a company and initiate the advancement of the Japanese clinical genomics market?” This preliminary thought was soon became something bigger when the duo came across a thought-provoking scientific article. According to the article, an endometrial microbiome analysis revealed that the bacterial balance in the uterus could associate with pregnancy rate. The dynamic duo believed that many infertile couples can benefit if this analysis was developed as a clinical testing service. And the rest, as they say, is history. On February 20th, 2017, Sakuraba, Ph.D. and the CEO of Varinos, and Yoko, Ph.D. and its CTO, co-founded the genomic clinical testing company. Today, the Varinos’ unique new-generation genomics testing in the field of reproductive medicine helps doctors clarify the causes of implantation failure and miscarriage, and aims to improve pregnancy outcomes.
Predicaments Still Lingered
As Sakuraba and Yoko began their journey toward the practical use of endometrial microbiome tests, they soon faced a major roadblock. One of the greatest challenges in endometrial microbiome analysis was to minimize the effect of environmental bacteria, which could confuse physicians when reporting the results. Although the use of Next-Generation Sequencing (NGS) technology could help in detecting bacteria in the uterus—which contains extremely low biomass—eliminating the noise coming from environmental bacteria was important to avoid false results during the analysis of bacterial load.
We have succeeded in detecting ureaplasma in low biomass amniotic fluid samples and helped physicians select appropriate antibiotics quickly, even though the culture test result was negative
With its distinctive inventions in endometrial microbiome analysis, Varinos minimized the effect of environmental bacteria and also established a comprehensive method to detect uterine-derived bacteria. “With the conventional method of culturing bacteria from vagina or uterus to detect bacteria in the genital tract, the sensitivity is low and only limited bacteria could be detected,” says Sakuraba. “Our mission is to apply genomic technology for medical practice in a timely manner. We developed several home-grown technologies and applications using NGS and provide entirely new clinical tests.”
The Reproductive Health Innovators
With a focus on the reproductive health space, Varinos currently provides PGT-A (preimplantation genetic testing for aneuploidy) and endometrial microbiome tests for infertility. Using these genomic technologies, the company improves pregnancy rates and lowers miscarriage rates. Through its collaborative researches, Varinos has helped many infertile patients to conceive after prebiotic interventions based on the tests.
Perinatal physicians can leverage Varinos’ test to find pathogenic bacteria from patients suffering from threatened premature delivery with a high fever. “While mycoplasma
are pathogenic bacteria which cause premature delivery, conventional culture methods fail to detect these bacteria. “However, we have succeeded in detecting ureaplasma
in low biomass amniotic fluid samples and helped physicians select appropriate antibiotics quickly, even though the culture test result was negative,” mentions Yoko. Further, Varinos conducts quality control (QC) at key points as part of the inspection process, thoroughly controls the quality, and incorporates an experiment management system and data analysis automation to minimize human error.
What steers Varinos ahead of the competition is its outstanding capacity to drive technological development in the NGS arena, highly specialized employees, and its network of key opinion leaders (KOLs) in academia and clinical field. To further improve its portfolio, Varinos shares the solution milestones to stockholders every month while the timeline of the next few months is shared with all the employees as well weekly.
Advancements in the solution’s capability are reported by specific teams daily, such that the managers can understand the on-site priority. “As a result of this strategy, we achieved the first practical use of endometrial microbiome test with a very short development period,” adds Yoko.
Connecting with Clients
As a part of its culture, Varinos’ common understanding is ‘Everyone has to fill the missing part for the company and innovate.’ Going a step further, Varinos always asks customers to collaborate in R&D by using its technology. “Because we are the only players that can analyze microbiome in ultralow biomass samples, like amnio fluid or endometrial fluid—even from a Gram-stained 9-year-old slide sample—we succeed in delivering microbiome analysis,” states Yoko.
These endeavors have helped the company carve a niche in the genome industry which has ultimately resulted in presentations at various conferences and in receiving many accolades. Varinos has already published three scientific papers as a result of the collaborations with customers and is also attending ESHRE in Vienna, which is one of the largest conferences in reproductive medicine. “The number of attendees is about 10,000. We had three presentations at this conference and one of those was by Yoko. She presented the collaboration results in front of an audience of 1,800 and showcased that the research capability is one of our strengths,” mentions Sakuraba.
The Torchbearers of a Novel Paradigm
Varinos has established the world’s first clinical laboratory endometrial microbiome analysis test service and has already analyzed more than 5,000 infertile samples. Using in-house data, the company continuously updates its tests to be more accurate such that it can detect “species” level microbiome. “To unlock the power of genome for humanity, we are planning to start the following tests: PGT-SR (preimplantation genetic testing for structural rearrangement) for pregnancy success, PGT-M (preimplantation genetic testing for monogenic diseases), and PGT-P (preimplantation genetic testing for polygenetic diseases). We respond quickly to new technological advances and always work toward including those in our solutions,” says Sakuraba.
"We developed several home-grown technologies and applications using NGS and provided entirely new clinical tests"
Varinos is also developing a new version of its genome analysis method by using machine learning. Genital microbiota is known to associate with genital diseases such as endometrial cancer, HIV infection, HPV infection, endometriosis, endometritis, recurrent implant failure, chorioamnionitis, preterm birth, low progressive motile spermatozoa, and low sperm concentration. To this end, Varinos’ well-established technology applies to any low biomass microbiome analysis and can accelerate research. For the near future, the company plans to expand its services worldwide and is looking for clinical test partners overseas. “Our mission is to continue delivering new genomic tests to the market on time. Genomic technology plays a critical role in reproductive health, genetic diseases or oncology, and inpatient care. Based on the demand in medical practice, we will work on new testing mechanisms that will create a new paradigm in the genome space,” concludes Yoko.