Xeno Biosciences has initiated a Phase 1b clinical study designed to provide proof-of-concept weight loss results, along with safety and tolerability, using an optimised formulation of the drug candidate XEN-101, in adults with obesity.
Xeno is advancing its lead development candidate, XEN-101, to address the unmet need for an effective, well-tolerated, orally administered obesity treatment. With a new understanding of the underlying mechanism of action of Roux-en-Y Gastric Bypass Surgery,
Xeno has developed a substitute for gastric bypass in a daily oral pill. XEN-101 has been shown to have wide safety margins and high tolerability in initial clinical trials.
XEN-101 is a gut-restricted, non-systemic compound with excellent safety profile observed in preliminary animal tox studies. XEN-101 is designed to deliver molecular oxygen to the lower gut in a targeted fashion to modulate the gut microbiome and intestinal environment. Delivery of oxygen to the distal gut generates a new environment in the gut, driving a shift in microbiota manifested by increased aerotolerant bacteria abundance.
The altered gut microbiota and luminal environment drives a weight loss response, which is thought to be triggered by neuronal and immune signalling from the gut to the brain (gut-brain axis).
The Phase 1b study is a double blinded, randomised, placebo controlled, parallel group design testing multiple doses of Xen-101 vs. placebo over four-week period in 32 adults with BMI 30-45 kg/m2. The study is being conducted in Australia and safety, tolerability, and total body weight change at the four-week endpoint will be the primary objectives. Pharmacodynamic effects, including microbiome composition, serum ketone levels, metabolic biomarkers, and changes in self-reported appetite and hunger will also be investigated.
“We’re confident that this study design will deliver proof-of concept body weight reduction results after 4-weeks of therapy in the background of already documented excellent safety and tolerability profile,” said Dr Dennis Kim, President and CEO of Xeno Biosciences. “With a daily oral administration schedule and a novel and differentiated mechanism of action, we believe Xeno is well-positioned to demonstrate Xen-101 as a new, exciting, and sought-after drug candidate that can address the strong and remaining unmet needs in the obesity field.”
The results of the Phase 1b study are expected by the end of 2024.