Synlogic has treated the first healthy volunteer in its Phase 1 study of the investigational Synthetic Biotic medicine SYNB8802 for the treatment of Enteric Hyperoxaluria (HOX). Enteric Hyperoxaluria is an acquired metabolic disorder caused by increased absorption of dietary oxalate, which is present in many healthy foods, making it almost impossible to control with diet alone.
Enteric Hyperoxaluria often occurs as a result of a primary insult to the bowel, such as inflammatory bowel disease, short bowel syndrome or as a result of surgical procedures such as Roux-en-Y bariatric surgery. Enteric Hyperoxaluria results in dangerously high levels of urinary oxalate, which causes progressive kidney damage, kidney stone formation and nephrocalcinosis. There are no approved treatment options.
"We are thrilled to be moving SYNB8802 into the clinic ahead of schedule," said Aoife Brennan, Synlogic's President and Chief Executive Officer. "Leveraging our Synthetic Biotic platform allowed us to move rapidly from candidate declaration to the initiation of the Phase 1 study in under nine months. Patients with dangerously high urinary oxalate levels today have few options, and we will move this program forward with a sense of urgency to meet their needs."
SYNB8802 is an engineered non-pathogenic strain of E. coli (Nissle), using Synlogic's Synthetic Biotic platform, designed to consume oxalate in the GI tract and lower urinary oxalate levels, potentially reducing kidney damage due to Enteric Hyperoxaluria. SYNB8802 is administered orally.
Synlogic recently presented preclinical data on SYNB8802 at the American Society of Nephrology's (ASN) Kidney Week 2020. The key finding from that study were:
- SYNB8802 consumes oxalate and produces formate, a metabolite of oxalate, in vitro.
- In both nonhuman primate and mouse models of acute Hyperoxaluria, SYNB8802 significantly reduced oxalate levels at six hours relative to vehicle alone.
- Proprietary in-silico simulations of predicted human exposure suggest SYNB8802 has the potential to achieve between 20% and 50% urinary oxalate lowering in patients at doses that have been well tolerated in prior trials of Synthetic Biotic medicines.
"The Phase 1 clinical study will provide for a rapid proof of concept read out by focusing on both an initial healthy volunteer cohort as well as a cohort of patients with Enteric Hyperoxaluria after Roux-n-Y gastric bypass surgery," said Dr Richard Riese, Synlogic's Chief Medical Officer. "This post-gastric bypass population provides an optimal cohort to assess the ability of SYNB8802 to lower urinary oxalate. We look forward to providing further updates as the study progresses."
The Phase 1 clinical study has two parts:
- Part A is a multiple ascending dose study in healthy volunteers
- Part B is a placebo controlled, cross-over design study in patients with Enteric Hyperoxaluria following Roux-n-Y gastric bypass surgery.
SYNB8802 will be assessed for safety and tolerability, and the potential to reduce urinary oxalate. Synlogic anticipates data from the study will be available in 2021.