XEN-101, Xeno's lead product candidate, is an oral-pill formulation designed to deliver molecular oxygen to the lower gut
Delivery of oxygen to the distal gut drives a microbiome shift and weight loss in a similar manner as Roux-en-Y Gastric Bypass (RYGB) surgery.
XEN-101 has shown profound weight loss efficacy in human subjects and animal models.
XEN-101 is designed to mimic RYGB, based on a mechanism of action described here as "Air Hypothesis":
RYGB leads to rapid and excessive transit of swallowed air (oxygen) into the colon.
Oxygen alters the gut chemical environment and microbiome (bacteria, fungi, archaea, viruses).
Altered neuro-immune signaling from the gut to the brain leads to weight loss.
Air Hypothesis is derived from the following facts:
(1) Humans swallow many liters of air into the stomach during the day.
(2) Stomach and pylorus normally prevent air from passing into the small bowel.
(3) RYGB abrogates stomach’s function to keep out air from the small bowel (Levine 2014).
(4) Small bowel transfers intra-luminal air rapidly to the proximal colon, where excess oxygen can alter the growth dynamics and function of the colonic gut microbiome.
Gas mixtures, with partial pressures (N2 & O2) equivalent to venous blood gas tensions, transit rapidly to colon with minimal absorption after jejunal infusion in healthy subjects (Dainese 2003).
RYGB patients experience large increase in flatulence symptoms despite negligible food malabsorption.
Similarly; people, who are unable to belch, suffer from excessive flatulence due to air transit to colon (Bastian 2019).
(5) RYGB drives an expansion of aerobic microbes in the gut. Transfer of fecal material from rodents or humans, who had RYGB, into germ-free mice leads to fat mass reduction in the recipient animals (Liou 2013).
(6) Construction of an unhindered, low pressure route from the esophagus to the small bowel leads to weight loss regardless of GI surgery type.
Roux-en-Y gastric bypass (RYGB)
Mini-gastric bypass (MGB)
(7) Proximal bypass or resection of the small intestine (without bypass of the stomach) does not lead to significant weight loss or change in gut microbiome, despite causing exaggerated post-prandial release of incretins (GLP-1, PYY etc.).
Duodenal-jejunal Bypass (DJB)
Ileal transposition (IT)
Bile diversion to jejunum
Small intestinal resection (<50%)