Kidney Week

Abstract: PO0650

Development of a Synthetic Biotic, SYNB8802, for the Treatment of Enteric Hyperoxaluria

Session Information

• CKD Mechanisms - 2
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2103 CKD (Non-Dialysis): Mechanisms

Authors

• Renaud, Lauren, Synlogic, Cambridge, Massachusetts, United States

Lauren Renaud,

• Lubkowicz, David, Synlogic, Cambridge, Massachusetts, United States

David Lubkowicz,

• Reeder, Pip, Synlogic, Cambridge, Massachusetts, United States

Pip Reeder,

• Bergeron, Chris, Synlogic, Cambridge, Massachusetts, United States

Chris Bergeron,

• Chen, Zhibin Courtney, Synlogic, Cambridge, Massachusetts, United States

Zhibin Courtney Chen,

• James, Michael J., Synlogic, Cambridge, Massachusetts, United States

Michael J. James,

• Cantarella, Pasquale, Synlogic, Cambridge, Massachusetts, United States

Pasquale Cantarella,

• Charbonneau, Mark, Synlogic, Cambridge, Massachusetts, United States

Mark Charbonneau,

• Shmueli, Ron, Synlogic, Cambridge, Massachusetts, United States

Ron Shmueli,

• Gao, Jr, Synlogic, Cambridge, Massachusetts, United States

Jr Gao,

• Isabella, Vincent, Synlogic, Cambridge, Massachusetts, United States

Vincent Isabella,

• Perreault, Mylene, Synlogic, Cambridge, Massachusetts, United States

Mylene Perreault,

Background

Enteric hyperoxaluria (EH) is a metabolic disease that results from excessive absorption of oxalate from dietary sources. Increased oxalate levels can lead to the formation of kidney stones and, ultimately, to kidney failure. EH occurs most frequently in patients with underlying gastrointestinal disorders, including inflammatory bowel disease, short bowel syndrome, or individuals who have undergone bariatric surgery. There is a high unmet need for new EH therapies, as a low oxalate diet is the only option currently available to patients. Synlogic is developing a novel Synthetic Biotic^TM medicine for the treatment of EH, designated as SYNB8802.

Methods

SYNB8802 is an engineered bacterium derived from Escherichia coli Nissle 1917 (EcN) that has been engineered to metabolize oxalate to formate and CO₂ in the gastrointestinal tract.

Results

Inoculation of SYNB8802 into minimal media showed significant consumption of oxalate and production of formate as compared to un-engineered (EcN) bacterial strain. When administered concomitantly with ¹³C-oxalate to healthy mice, SYNB8802 decreased the urinary recovery of ¹³C-oxalate, indicative of its ability to consume oxalate in vivo. In healthy non-human primates (NHP) administered approximately 400 mg of dietary oxalate, SYNB8802 lowered the urinary recovery of oxalate and ¹³C-oxalate in a dose dependent manner by up to 75% as compared to vehicle. In addition, Synlogic has developed a mathematical model that predicts clinically meaningful reductions in urinary oxalate in EH patients.

Conclusion

Overall, SYNB8802 represents a promising new approach for the treatment of enteric hyperoxaluria.