Synlogic Announces Achievement of Proof of Concept for SYNB8802 in Enteric Hyperoxaluria Based on Urinary Oxalate Lowering in Phase 1b Study

Synlogic, Inc. recently announced that SYNB8802 has demonstrated proof of concept through clinically significant lowering of urinary oxalate in a Phase 1b study in patients with a history of gastric bypass surgery.

“Given the profound need for a medical treatment for enteric hyperoxaluria, we are delighted to demonstrate meaningful reductions in urinary oxalate in the Roux-en-Y gastric bypass patient population,” said Aoife Brennan, MB, ChB, Synlogic President and Chief Executive Officer. “In addition, this important milestone represents the third positive clinical data readout this year in three different diseases, following our positive Phase 2 results for SYNB1934 for phenylketonuria and positive Phase 1 results for SYNB1353 for homocystinuria.”

“A subset of enteric patients have repeated kidney stones and life-altering disease that is particularly challenging to manage,” added Kyle Wood, MD, Associate Professor of Urology at the University of Alabama at Birmingham. “A therapeutic approach that lowers urinary oxalate in patients with underlying GI malabsorption is badly needed. The innovative mechanism of SYNB8802 and the strength of the data generated to date support the potential for SYNB8802 to be a highly meaningful first-in-category biotherapeutic.”

This Phase 1b study was a double-blind, randomized, placebo-controlled, inpatient study evaluating the safety and tolerability of SYNB8802 in subjects with a history of Roux-en-Y gastric bypass surgery. The primary endpoint was safety and tolerability. After a 3-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 six days at the 3 × 10¹¹ live cell dose. Each 6-day treatment period included a stepwise increase in dose frequency. To enable a controlled assessment of SYNB8802’s effects on oxalate, 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; 7 received SYNB8802 and 4 received placebo. SYNB8802 was well tolerated, with no SAEs. The most common AEs were GI-related, mild, and transient. The GI-related AEs occurred at a similar frequency in active and placebo groups. One 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. In a pharmacometric analysis that takes into account all patients’ data, dose level and dose frequency, there was a -28% (-37.2, -18.2) change from baseline in urinary oxalate vs. placebo at the 1×10¹¹ TID dose, and a -38% (-46.4, -28.7) change from baseline in urinary oxalate vs. placebo at the 3×10¹¹ TID dose.

In addition to the completed SYNB8802-CP-002 study, SYNB8802 is also being evaluated in an ongoing, outpatient study (SYNB8802-CP-001).   Full results from both studies will be presented at a future medical meeting.

Enteric hyperoxaluria (EH) is a metabolic disease and well-recognized cause of recurrent kidney stones, typically caused by a chronic underlying GI disorder associated with malabsorption, which predisposes patients to excessive absorption of oxalate. Elevated oxalate in the circulation leads to oxalate crystal formation in the kidney, causing excruciating pain and progressive renal damage. There is no FDA-approved treatment for enteric hyperoxaluria. SYNB8802 is a novel, orally administered, non-systemically absorbed drug candidate being developed for the treatment of enteric hyperoxaluria. SYNB8802 was designed using precision genetic engineering of the well-characterized probiotic E. coli Nissle to metabolize oxalate in GI tract, preventing its absorption and resultant crystal formation, lowering levels of urinary oxalate.

Synlogic is a clinical-stage biotechnology company developing medicines through its proprietary approach to synthetic biology. Synlogic’s pipeline includes its lead program in phenylketonuria (PKU), which has demonstrated proof of concept with plans to start a pivotal, Phase 3 study in the first half of 2023, and additional novel drug candidates designed to treat homocystinuria (HCU), enteric hyperoxaluria and gout. The rapid advancement of these potential biotherapeutics, called Synthetic Biotics, has been enabled by Synlogic’s reproducible, target-specific drug design. Synlogic uses programmable, precision genetic engineering of well-characterized probiotics to exert localized activity for therapeutic benefit, with a focus on metabolic and immunological diseases. In addition to its clinical programs, Synlogic has a research collaboration with Roche on the discovery of a novel Synthetic Biotic for the treatment of inflammatory bowel disease or IBD. Synlogic has also developed two drug candidates through a research collaboration with Ginkgo Bioworks: SYNB1353, designed to consume methionine for the potential treatment of HCU, and SYNB2081, designed to lower uric acid for the potential treatment of gout. For more information visit www.synlogictx.com.