Kyle Wood, MD, Associate Professor of Urology, University of Alabama ​at Birmingham, discusses the results of the phase 1b study evaluating SYNB8802 for the treatment of enteric hyperoxaluria. 

Enteric hyperoxaluria is a rare metabolic disorder characterized by excessive absorption of dietary oxalate. It is often caused by Roux-en-Y gastric bypass surgery or an underlying malabsorption-associated chronic gastrointestinal disorder. Elevated oxalate in the blood leads to crystal formation in the kidneys causing kidney stones, excruciating pain, and progressive renal damage. There is currently no FDA-approved treatment for enteric hyperoxaluria.

As Dr. Wood explains, SYNB8802 is an orally administered, non-systemically absorbed drug candidate being developed for the treatment of enteric hyperoxaluria. SYNB8802 uses a probiotic E. coli Nissle to metabolize oxalate in the GI tract, preventing its absorption and subsequent crystal formation, and lowering levels of urinary oxalate.


The phase 1b study was a double-blind, randomized, placebo-controlled, inpatient study evaluating SYNB8802 in subjects with a history of Roux-en-Y gastric bypass surgery. The primary endpoint was safety and tolerability. After a three-day diet and placebo run-in, patients were randomized to either placebo or SYNB8802 for a 12-day dosing period. The dosing period included a dose escalation plan with the first 6 days at the lower dose of 1 × 1011 live cells, followed by 6 days at the 3 × 1011 live cell dose. Each 6-day treatment period included a stepwise increase in dose frequency. Patients consumed a controlled diet for the duration of the inpatient stay. Urine was also collected for a 24-hour sample for each patient, each day.

The study enrolled 11 patients; seven received SYNB8802 and four received a placebo. SYNB8802 was well tolerated, with no serious adverse events (AEs). The most common AEs were GI-related and were mild and transient. The GI-related AEs occurred at a similar frequency in the treatment and placebo groups. 1 patient in the placebo group discontinued during dosing due to the need for antibiotics.

Dosing with SYNB8802 was associated with a dose-dependent reduction in urinary oxalate. A pharmacometrics analysis found there was a -28% change in urinary oxalate vs. placebo at the 1×1011 dose and a -38% change from baseline in urinary oxalate vs. placebo at the 3×1011 dose.

As Dr. Wood notes, these results are highly positive, demonstrating both the safety of SYNB8802 as well as its potential efficacy as a therapy for enteric hyperoxaluria. The next steps include a study where the reduction of stone events is an evaluated endpoint.

To learn more about enteric hyperoxaluria and other rare metabolic disorders, visit