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

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

Authors 

Renaud, L., Synlogic
Reeder, P. J., Synlogic Inc
Ghoshal, S., Synlogic
Bergeron, C., Synlogic
Chen, C., Synlogic
James, M., Synlogic Inc.
Cantarella, P., Synlogic
Charbonneau, M., Synlogic Inc
Shmueli, R., Synlogic
Gao, J., Synlogic
Puurrunen, M., Synlogic
Isabella, V., Synlogic Inc.
Perreault, M., Synlogic
Enteric hyperoxaluria (EH) is a human metabolic disease that results from excessive absorption of oxalate from dietary sources. High urinary oxalate levels (UOx) in patients with enteric hyperoxaluria (EH) can lead to recurrent kidney stones, nephrocalcinosis and chronic kidney disease (CKD). EH disproportionately impacts patients who have undergone certain kinds of gastric bypass surgery and can lead to significant kidney complications in those patients. It also occurs in patients with underlying GI disorders including Crohn’s disease or short bowel syndrome. There is a high unmet need for new EH therapies as there are currently no approved pharmacological therapies for treating hyperoxaluria. Synlogic is developing a novel Synthetic BioticTM medicine for the treatment of EH, SYNB8802. 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. When SYNB8802 was administered concomitantly with 13C-oxalate to healthy mice, it decreased the urinary 13C-oxalate, which is indicative of its ability to consume oxalate in vivo. In healthy non-human primates (NHP) administered ~400 mg of oxalate, SYNB8802 dose-dependently lowered the urinary oxalate and 13C-oxalate by up to 75% as compared to vehicle. In addition, Synlogic has developed a mathematical model that is predicting clinically meaningful reductions in urinary oxalate in humans. SYNB8802 is currently in Phase 1 clinical trials in healthy volunteers and patients with EH secondary to Roux-en-Y gastric bypass surgery. Overall, SYNB8802 represents a promising new approach for the treatment of enteric hyperoxaluria.