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Startup Nephrosant Aims to Launch Noninvasive Kidney Transplantation Test by Early 2020

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SAN FRANCISCO – Bay Area startup Nephrosant, a University of California, San Francisco spinout, aims to launch its first noninvasive test for detecting kidney injury by early next year.

Nephrosant, formerly known as KIT Bio, has around 10 employees and has raised about $3 million in seed financing, said Minnie Sarwal, the company's cofounder and a professor of surgery at UCSF. The company plans to start a Series A financing round next year.

Nephrosant aims to noninvasively assess kidney health starting with the kidney transplantation field. It plans to launch tests in 2020 for living kidney donors to analyze the health of the remaining kidney and for transplant recipients to monitor for rejection, Sarwal said. Eventually, Nephrosant also aims to develop tests outside of the transplantation field, including for individuals at high risk of kidney disease.

Nephrosant's initial assay will analyze six biomarkers from urine: the amount of cell-free DNA, the fraction of methylated cell-free DNA, the proteins clusterin and creatinine, the inflammation marker CXCL10, and total protein.

In a validation study published in April in the Journal of Clinical Medicine, the researchers tested the assay on 397 urine samples, and found that it had a sensitivity and specificity of 97.3 percent and 94.1 percent, respectively, for determining high versus low risk of chronic kidney disease.

Sarwal said that the same biomarkers are also relevant for a transplantation test and that the team would just need to tweak the algorithm. She noted that the company plans to first focus on this application because there is already an established pathway toward reimbursement for similar noninvasive tests such as those offered by CareDx and Natera.

Like those tests, Nephrosant's assay analyzes cell-free DNA but does not use next-generation sequencing or amplification. Instead, it uses a proprietary ELISA method that involves a 5' biotinylated oligonucleotide immunoprobe to target cfDNA fragments. The ELISA technique is also used to analyze the proportion of cfDNA that is methylated. The protein markers, meanwhile, increase the sensitivity of the test. "The different components tell a different story about kidney injury," Sarwal said.

Looking at more than one type of biomarker makes the assay more robust and quantitative, providing a "more comprehensive analysis of what's happening in the kidney," Sarwal said.

Using ELISA as opposed to sequencing or PCR also keeps the cost of the test low, she added.

The initial version of the test will be commercialized as a laboratory-developed test out of a central lab, but Sarwal said that the team is also collaborating with SRI International and DCN Diagnostics in San Diego to develop a dipstick version of the test that could be analyzed at the point of care.

While CareDx and Natera's tests are both for monitoring kidney transplant recipients, Sarwal said that monitoring living donors would be an important application of Nephrosant's assay, particularly since it is an unmet need.

Sarwal pointed to an April JAMA Network Open study she coauthored, which evaluated 9,558 living kidney donors. The study found that 1,406 donors, or 14.7 percent, had post-donation events that included hypertension, diabetes, proteinuria, and post-operative intestinal complications.

Most transplant programs are required to follow up with kidney donors for two years, but in the JAMA Network Open study, the UCSF researchers found that donors can have adverse events as far as 40 years after donation, suggesting the need for longer-term monitoring. 

Ultimately, Nephrosant's test will have utility in screening and predicting risk of developing kidney disease, Sarwal said. She didn't provide a timeline for such a test but said that it would be based on the same six biomarkers and risk prediction score described in the Journal of Clinical Medicine study. Initially, the company would launch a test for individuals already at higher risk of developing kidney disease due to diabetes or obesity, for instance.

Another differentiator of Nephrosant's test is that it analyzes a urine sample, as opposed to blood, so is less invasive and easier to do serial screenings. She noted that the team has developed a preservative solution to prevent the cfDNA from degrading when samples are not able to be processed immediately, making the test more flexible and able to fit in to a physician's clinical workflow.

Separately, Sarwal's team at UCSF continues to do research in the transplantation field. "The way we manage transplant patients today is a one-size-fits-all approach," she said. One area of research her team is pursuing is in understanding how individuals' immune repertoires may shed light on a person's inherent risk.

Her group has collaborated with Adaptive Biotechnologies to do immune repertoire sequencing to better understand patients' risk for rejection. The goal is to try and see if, prior to transplantation, the immune repertoire is predictive of either a good outcome or rejection, which could enable physicians to tailor immunosuppressant therapies appropriately, she said. Keeping patients on immunosuppressants who don't need them is undesirable because such drugs can increase their likelihood for infection and even cancer, but taking a patient off the medications too soon can lead to transplant rejection.

Sarwal said that this research is still very early-stage but that the data is promising. For instance, in a study published in April in Nature Communications, the UCSF team sequenced the B cell receptors of 27 individuals and found a set of clones that were expanded before transplantation only in those patients who ultimately experienced rejection. The researchers plan to follow up with larger studies.