Xeragenx is developing a receptor-targeted oral B12™ prescription product [XGX-001] that provides an optimal dose of B12 (Cbl) pre-bound to human IF for physiologic absorption. This illustration depicts the number of advantages that XGX-001 can deliver for avoiding the obstacles that often prevent normal absorption of vitamin B12.
① XGX-001 provides vegetarians and vegans an oral form of B12 that will alleviate the need to obtain a dietary source of Cbl from animal based foods. A daily ingestion of the Xeragenx tablet will provide enough B12 to maintain a person’s physiologic needs without exposing the body to mega doses of supplemental B12.
② Providing XGX-001 will circumvent the common problem of inadequate acid or pepsin secretion in the stomach that prevents dietary Cbl from being utilized in the body. Without acid and pepsin secretion, food-based Cbl cannot be severed from the animal protein and becomes unavailable for absorption.
③ XGX-001 bypasses the Cbl-R binding step in the stomach and subsequent release in the upper duodenum prior to intrinsic factor capturing Cbl for final transport. This is accomplished with an enteric coating that will seal the Cbl-rhIF inside the tablet until reaching the upper duodenum, increasing absorption certainty with the ingested dose of Cbl at its targeted receptor.
④ Providing a pre-bound form of Cbl to rhIF avoids the serious problem of inadequate secretion of intrinsic factor from parietal cells. Without sufficient native intrinsic factor, free Cbl cannot be physiologically absorbed.
⑤ Because the transfer of Cbl from R to IF requires pancreatic enzyme release to degrade R, any impairment of normal pancreatic function can prevent Cbl absorption. XGX-001 avoids the problem because the pre-bound Cbl-rhIF bypasses the need for the R-binding and release steps altogether.
⑥ The product is designed to degrade its enteric coating at a pH range and location where native intrinsic factor normally binds free Cbl and will not be interfered with by R-binding protein (depicted by the yellow tablet coating being degraded).
⑦ Providing a receptor-targeted dose of oral B12 that is pre-bound to rhIF avoids the problem of bacterial competition by protecting the Cbl from uptake and utilization by the normal flora of the terminal small bowel.
⑧ After degradation of the enteric coat, the Cbl-rhIF complex travels to the distal ileum where it binds to the cubilin receptor. The cubilin receptor shows specific binding only with Cbl-IF, but not with free Cbl, free R (HC), or free IF.
⑨ Upon cubilin-mediated internalization of the Cbl-rhIF, the rhIF is degraded in the lysosome, and after a delay of 3 to 4 hours, Cbl appears by itself bound to TC I (HC) and TC II (TC) in the portal bloodstream.
Finally, when mega doses of B12 (200-1000 times the physiologic requirement) are orally ingested with only a 1% absorption rate, the vast majority of unabsorbed Cbl is utilized by bacteria to produce even larger amounts of cobalamin analogues. These analogues can also be passively absorbed, and likely at higher rates of absorption than 1%. Any resulting interposition of analogues in the place of Cbl can interrupt fundamental enzymatic processes necessary for normal neurologic function, DNA synthesis, and red blood cell production.
A receptor-targeted oral B12™ pre-bound to rhIF can overcome the number of obstacles that prevent the vitamin from being properly bound, transported, absorbed, and utilized. XGX-001 will deliver a highly absorbable oral B12 at the body’s intended physiologic dose and avoid the consequences associated with ingesting B12 in mega dose quantities, which are often a thousand times greater than the physiologic receptor capacity.