NEW YORK (GenomeWeb) – Nearing completion of a multicenter validation study, MDx startup Episona anticipates launching its sperm methylation test to diagnose male infertility and predict IVF success by the end of the third quarter this year.
Alan Horsager, co-founder, president, and CEO of Episona, told GenomeWeb that he and other co-founders started the company from an initial interest of predicting the health of future offspring — particularly the development of neurological disorders — based on analysis of a parent's sperm DNA.
While that is still a long-term goal, Horsager said that Episona decided to first tackle a target with more immediate clinical relevance and a more direct path to commercialization — male infertility.
The firm's approach relies on Illumina HumanMethylation450 Bead Chip arrays to measure genome-wide sperm DNA methylation patterns in order to predict male fertility status and resulting embryo quality.
Episona, with collaborators at the University of Utah, published an initial proof of concept study of its approach last year in the journal Fertility and Sterility.
That study — led by the University of Utah's Douglas Carrell and USC's Andrew Smith, two other co-founders of Episona — looked retrospectively at samples from 127 men from couples undergoing IVF treatment.
The researchers stratified the IVF patient cohort into two groups: choosing about 50 who ended up having fairly good embryogenesis and a positive pregnancy, and another 70 who had relatively poor embryogenesis after IVF, with some achieving pregnancy and some not. For all these couples, major female factors contributing to infertility had been ruled out as a cause. The study then compared these two groups to samples from 54 normal sperm donors with proven fertility.
Using their array-based strategy for methylation profiling, the team was able to develop a predictive model that distinguished male fertility status with 82 percent sensitivity and a 99 percent positive predictive value.
According to Horsager, when trying to predict both the male contribution to a couple's infertility and resulting embryo quality, the sensitivity of the company's technology drops, but its specificity remains high. In the proof-of-concept study, the group saw up to 50 percent sensitivity with no false positives in predicting good embryos and successful pregnancy.
Because of the clinical niche for the test, specificity is the more important measure, Horsager explained, since it's important to minimize the risk of a false positive result that rules out successful pregnancy for a couple.
Since publishing that study, the company has been pursuing a multi-center prospective validation of these initial results, recruiting about 400 patients through 10 different clinical sites, including IVF centers in Toronto, Atlanta, Los Angeles, and Seattle.
Though he could not share details about the results, Horsager said Episona has already analyzed some early data, finding that the test's sensitivity and specificity appear to be encouraging according to what investigators expected from their initial proof of concept.
As the study concludes, the company has been simultaneously setting itself up for a commercial launch intended hopefully by the end of the third quarter this year. Horsager said he and colleagues started raising money to support this path forward beginning in early 2015, netting about $1.35 million in angel capital.
The company plans to offer its test as an LDT, and is working now on moving through CLIA certification and California licensure of its lab.
For initial wet lab sample processing, the company is going to partner with LabCorp subsidiary the National Genetics Institute. Episona will then perform data analyses in its own CLIA facility.
According to Horsager, the company's commercial strategy will be to seek out customers in the IVF lab market. Fertility treatment is largely self-paid, so in some ways the company looks at individual patients as its customers, but it will directly market the test to the companies and centers that offer IVF services to these individuals.
To that end, many of the centers participating in the company's current prospective validation study would be potential target customers once the company launches commercially later this year, Horsager said.
Currently, DNA fragmentation is used in the male fertility diagnostic space, but Horsager said that the validity and utility of such tests remain relatively unproven compared to the manner in which Episona intends to validate its methylation approach.
Genetic tests also exist currently to identify molecular causes of azoospermia, or impaired sperm production. For example, MDx firm Elucigene launched a PCR-based Y-chromosome microdeletion test in Europe last year for testing men with impaired spermatogenesis.
According to Horsager though, such testing doesn't overlap with Episona's mission, which is to identify male infertility in couples where there isn't already a clear answer like an absence of sperm.
Moving forward, Horsager said that Episona is also planning to pursue research into other diagnostic or predictive uses of sperm methylation, which the company views as an analyte that has been relatively ignored in the MDx space so far.
"Obviously sperm is a gamete, it is what's contributing to the offspring, so we are interested in what's going on there and whether there are things that are changing that might impact the offspring," Horsager said.
In addition, the company wants to look at whether sperm epigenetics may also offer any diagnostic potential for disease risk in men themselves.
Finally, Horsager said, Episona is also researching whether sequencing technologies may offer a better analytic platform for its methylation analysis than the 450K arrays the company's test is currently built on.
Since the firm's predictive approach relies not on detecting specific methylated sites, but rather on measuring patterns of methylation over whole regions of the genome, deep sequencing coverage may not be necessary for achieving sufficient resolution. That could allow for lower-cost use of sequencing technologies that otherwise remain cost prohibitive compared to the 450K array technology, he said.