NEW YORK – Organ transplant diagnostics company Verici Dx aims to estimate kidney recipients' risk of transplant rejection prior to and after surgery by conducting gene expression-based immune system profiling in blood.
The firm, which incorporated in the UK but has since moved its headquarters to Franklin, Tennessee, has three tests in development: Clarava, Tutivia, and Protega. These provide rejection risk estimates pre- and post-transplant, as well as fibrosis and long-term graft failure risk post-transplant, respectively, all from gene expression profiles.
Clarava utilizes a 10-gene signature and Tutivia a 17-gene signature, while Protega is at an earlier stage of development.
Gene expression "is an earlier biomarker" than cell-free DNA, said Sara Barrington, Verici's CEO, explaining that the latter provides signals after damage has already occurred, whereas gene expression patterns can provide clues to how aggressively — or not — an individual's immune system is likely to respond to events such as an organ transplant.
"Your immune system is usually your best friend," Barrington said, "but for transplant patients, it can be a little confounding."
With respect to how a patient's immune system might react to a graft, Barrington said, clinicians are often "flying blind," beginning with a high immunosuppressant dose, tapering as quickly as possible, and essentially waiting to see what happens.
Patient care protocols, she said, need to be more personalized, but to do that, clinicians need more information, which is where Verici sees its products stepping in.
John Friedewald, a professor of medicine at Northwestern University and inventor of the TruGraf kidney transplant test, which is commercialized by Transplant Genomics, concurred, saying that "there's a lot of interest in trying to risk-stratify patients getting a transplant, because for decades we've had pretty much a one-size-fits-all approach."
Verici recently announced positive results from an ongoing validation study of Clarava, the firm's pre-transplant blood-based prognostic test for the risk of early acute kidney transplant rejection.
"Clarava," Barrington said, "asks the question, 'how aggressive or benign is the patient's immune system likely to be, in the event of a transplant?'"
The results of the study are not yet publicly available, as Verici has extended enrollment for a further six months in order to enrich the utility data for the assay and support the case for adoption. That study is taking place across 14 transplant centers within Europe and the US and aims to recruit a total of 550 participants.
"The data will be available once full data analysis has been completed with the extended cohort," Barrington said.
Friedewald mentioned that the "trick" to prospective risk stratification tests such as Clarava is that "none of the patients have been exposed to immune suppression yet [and] they haven't gone through surgery yet. There's a lot that happens afterwards."
Clarava, Tutivia, and Protega all sequence the entire blood transcriptome, which is analyzed by Verici's proprietary AI platform, which extracts RNA signatures based on the biological systems for inflammatory, immune, metabolic, and cell repair pathways, among others.
Taking place after transplantation, Tutivia assesses the risk of early acute rejection, addressing the question of how likely a patient is to be having a rejection event.
Barrington said that the potential for nonspecific results from cfDNA tests helps to drive interest in RNA-based risk assays.
Numerous phenomena cause cells to release DNA into the bloodstream, such as apoptosis and viral infections. Because of these confounding factors, "everyone's been moving away from cell-free DNA," said Barrington.
Friedewald characterized this shift less as a move away from cfDNA and more as a growing appreciation for using both cfDNA and RNA-based expression tests to gain a more complete picture of patient risk.
Last year, for instance, Friedewald and his colleagues published a study showing that combining donor-derived cfDNA and a gene expression test performed better than either one alone in diagnosing subclinical rejection.
"Combining tests is probably where we're going in the future," he said.
While Verici estimates that it can launch Clarava in roughly six months, the company is currently in the process of commercially launching Tutivia. Barrington said that Protega's commercial launch is set for approximately two years down the line.
Verici plans to announce pricing for Tutivia later this year, with MolDX-proposed pricing by the end of the second quarter of next year. The company expects Tutivia to be eligible for and covered by an existing local coverage determination issued by Palmetto under the MolDX program.
In Europe, Verici plans to seek CE marking for its test, according to its website, as well as UKCA (UK Conformity Assessed) marking in the UK.
Verici plans to extend its tests to other organs beyond the kidney in the future, although the details concerning when that will happen and which organs will be prioritized are not yet settled.
It may also consider commercial opportunities in other areas, such as autoimmune diseases.
"Whole RNA signatures [are] very applicable to other diseases," Barrington said, "and we have early data to show that it works in autoimmune diseases. That's a long-term vision."
In addition to organ transplant diagnostics, Verici has a robust data services business. The company's strategy of always sequencing the entire transcriptome allows it to generate large amounts of data that can be of interest to researchers across industry and academia.
The firm is collaborating with 14 academic institutions worldwide in validating its tests. Also, in January, it announced a collaboration with Illumina, which granted Verici early access to the Illumina Connected Analytics bioinformatics software platform in an effort to expedite the operational launch of Verici's data analytics and artificial intelligence components.
Verici was spun out from Renalytix, a UK kidney disease diagnostics company, last year, and Barrington said the two companies continue to work very closely together, sharing resources, ideas, and strategies. According to its website, Verici has an R&D sequencing lab in New York City and a CLIA lab in Franklin, Tennessee.
The firm recently posted a $15.7 million cash balance as of June 30, which is expected to last through to the start of 2024. Part of this came from $12.5 million in net proceeds Verici raised in March from issuing approximately 28.6 million new ordinary shares.
Barrington said that investors have been "happy" with the company's pace in moving from a pre-revenue R&D company to a fully commercial, revenue-generating one.
"We've never deviated from our milestones and funding plan," she said.