PN-943

Protagonist Therapeutics developed PN-943 for moderate-to-severe ulcerative colitis. It aims to act locally in the intestine as a peptide targeting the α4β7 pathway, the same broad homing pathway addressed by injectable antibody vedolizumab. A shared target does not establish equivalent clinical efficacy or approval.

Blocking α4β7 integrin on lymphocytes prevents interaction with MAdCAM-1 on gut blood vessels. That interaction helps inflammatory T cells migrate to intestinal lining. The oral gut-targeted strategy aims to reduce this traffic and inflammation; the mechanism is separate from whether a clinical remission endpoint is met.

Supporting references: α4β7 integrin.

An earlier Phase 2a program reported under PTG-100 missed its prespecified primary endpoint; a favorable low-dose signal emerged only after a blinded reread of endoscopy images. Subsequent company-reported, non-peer-reviewed IDEAL Phase 2 findings showed a lower-dose remission signal but not a higher-dose result, giving an inconsistent dose response. These findings do not establish efficacy.

PN-943 is not approved. After the Phase 2 readout, the company said an external partner would be needed to advance the program and shifted its focus elsewhere. No Phase 3 start or confirmatory result is established in the reported development account.