NEW YORK – Elypta, a Swedish diagnostics developer, has commenced a clinical trial of its metabolite-based liquid biopsy platform for the prognosis and potential guidance of treatment of muscle-invasive bladder cancer.
The 4-year-old firm this week also announced that it has expanded an ongoing trial of a test in development for recurrent kidney cancer. Elypta is also developing a third test for the early detection of multiple cancers, which the company believes could eventually be used for routine cancer screening.
"The bulk of our research to date has gone toward kidney cancer as our first indication," said CEO Karl Bergman in an interview this week. "Since we started Elypta though, we knew that our platform had a wider potential to detect cancer across classes," he said. "We were thinking of where it fit best, and bladder cancer is near the top of that list next to kidney cancer and a multicancer early detection test."
Elypta was founded in 2017 to commercialize technology developed at Chalmers University of Technology in Gothenburg. The firm is based in Solna, just outside Stockholm, and currently employs about 15 people, Bergman said. Its core platform is capable of measuring a panel of metabolites called glycosaminoglycans, or GAGs, in blood or urine in order to detect cancer.
According to Bergman, GAGs are measured via an enzymatic digestion assay that depolymerizes the metabolites into disaccharides, a class of sugars. These are then labeled and separated via ultra-high performance liquid chromatography and detected using electrospray ionization triple-quadrupole mass spectrometry through multiple reaction monitoring, he said. These measurements are then paired with an algorithm-based scoring system to provide results, which Elypta calls the GAG score.
Elypta's kits are manufactured by Merck KGaA. Bergman said that while the company plans to make its assay more widely available as a commercial product, it mostly uses the kits internally.
Its first indication of interest is renal cell carcinoma, the most common form of kidney cancer. The firm believes that as no liquid biomarker exists for renal cell carcinoma recurrence, it has a shot at offering the market something unique that could complement conventional approaches such as medical imaging. In 2019, Elypta received €2.4 million in Horizon 2020 funding from the EU to advance the program. The company commenced a clinical trial of the test last year, but this was slowed due to the pandemic. Elypta raised €6.1 million last year to continue, and Bergman said it is likely to raise more in 2022 to support various diagnostics programs.
This week, Elypta announced that it had added 10 sites to its kidney cancer recurrence trial, called the AUR87A study. The prospective study commenced in January 2020 in 16 sites across six countries in Europe and the US. Now 10 additional sites have been added. The company said that as of this week, it has screened more than 400 patients and enrolled more than 130 more. Recruitment is slated for completion in June 2022.
"This study started right when the pandemic started," acknowledged Bergman. "COVID-19 slowed us down, but now the sites are up again."
The network assembled for the kidney cancer study has also helped lay the foundation for Elypta's foray into bladder cancer, he added. "Many of the same people are deeply involved with bladder cancer in one way or another," said Bergman. "It is a neighboring indication."
For bladder cancer, Elypta's interest is not in early-stage detection, but in helping to guide treatment. As noted in a Dec. 8 statement from the company, about two-thirds of patients with muscle-invasive bladder cancer do not respond to neo-adjuvant chemotherapy. Elypta's test will enable clinicians to determine which patients have a poor prognosis versus those who might better respond to therapy, which usually includes chemotherapy followed by radical cystectomy.
Elypta has now embarked on a prospective study of its assay in bladder cancer patients to better hone its potential, based on promising internal work. "We see GAGs as a good tool to understand the aggressiveness and prognosis of muscle-invasive bladder cancer," said Bergman. "It's a smaller niche [than kidney cancer] but one with a clear need," he said. Bergman likened Elypta's envisioned test to Oncotype DX, a pioneer genomic assay to help determine the benefit of chemotherapy in breast cancer that was originally developed by Genomic Health, since 2019 a part of Exact Sciences.
Vinnova, the Swedish innovation agency, awarded Elypta around SEK 2.1 million ($230,000) last year to support a study called AUR93A involving its platform to guide bladder cancer treatment. It commenced earlier this month when the first patient was enrolled at San Raffaele Hospital in Milan. According to Bergman, Elypta plans to enroll 76 patients as part of AUR93A.
Multicancer early detection test
At the American Society of Clinical Oncology meeting, held virtually last June, Elypta published data around a third test it has in development, which it claims can detect a third of all stage I or low-grade tumors across tumor types, including genitourinary and brain tumors. Sensitivity to the cancers assessed was 31 percent in plasma and 33 percent in urine, with a false positive rate of 2 percent. The profiled study involved Chalmers University of Technology and surveyed 1,500 samples across 14 cancer types. According to Bergman, Elypta is now validating the study findings in another population and anticipates being able to share results from the complete study next year.
"This is a screening test for all cancers," said Bergman. "It's one test you take to catch any kind of cancer, perhaps once a year," he said. Elypta and its partners have yet to determine what age group the test will be routinely offered to, or how it will be used in a clinical setting, but said preliminary results have "given us a lot of confidence," and that Elypta will over the next two years move forward with clinical validation of its multicancer early detection test in the targeted screening population to support regulatory filings for market approval.
In general, Elypta is optimistic about its core concept of using metabolite signatures to guide cancer diagnosis and treatment. It's an approach that he noted is sometimes less apparent in a diagnostics landscape dotted with protein assays and genetic tests.
"The metabolism is overlooked," said Bergman. "We have collectively spent decades looking at proteins and now the genome, but the way we see it, the metabolome offers a different layer of information altogether." As such, Elypta will eventually look to build out its research business by selling kits.
"We won't be able to do all this work," remarked Bergman. "At one point, we will start selling the research-use-only kits more openly, but right now would like to keep the technology closer to heart and develop it further."