Oral α4β7 peptide · ulcerative colitis
An experimental oral peptide designed to calm gut inflammation in ulcerative colitis. It blocks α4β7, the same immune-cell target as the approved antibody vedolizumab, but it is taken by mouth and built to stay mostly inside the gut. It was developed by Protagonist Therapeutics and we found no approval anywhere.
Integrins are proteins on the surface of immune cells. By latching onto adhesion molecules, they let those cells travel into tissues, and α4β7 is the integrin that steers white blood cells toward the gut2. In inflammatory bowel disease, this traffic helps keep inflammation going. PN-943 binds α4β7 on white blood cells and is meant to block their movement into the gut and their activation there1. It is a gut-restricted peptide, so little of it is absorbed.
In healthy volunteers, blood levels stayed low, almost no intact drug reached the urine, and more intact drug appeared in stool as the dose rose. Even so, the share of α4β7 receptors it occupied on blood cells still rose with dose1. It follows PTG-100, an earlier gut-restricted α4β7 peptide from the same company2,3.
Human data are limited. In two phase 1 studies in healthy volunteers, PN-943 showed low exposure in the bloodstream, receptor occupancy in blood that rose with dose, and no withdrawals due to side effects1. Its predecessor, PTG-100, missed its primary endpoint in a phase 2a ulcerative colitis trial. A blinded re-read of the endoscopy videos by an outside group later suggested clinical and tissue-level benefit at some doses, and mouse work showed it reached gut lymphoid tissue and reduced memory T-cell trafficking3. PN-943 then entered a phase 2 trial in 169 adults with moderate to severe active ulcerative colitis. That trial compared two dose levels with placebo for clinical remission at week 12 and was completed in February 20234. No results have been posted to the registry, and we found no peer-reviewed report of them.
PN-943 is not approved by the FDA, and we found no approval by any other regulator; its only registered patient trial ended in 2023 without posted results4.
No side-effect profile from patients has been published. In the healthy-volunteer studies it was generally well tolerated, and no one stopped because of side effects1. Its predecessor PTG-100 was reported as well tolerated in phase 1 and 2 studies3. Side-effect results from the phase 2 ulcerative colitis trial have not been posted4.
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