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PN-943

EvidenceLow research

ClassOral α4β7 integrin antagonist peptide

PN-943 is an investigational oral peptide that blocks the alpha4beta7 integrin in ulcerative colitis. See how it works and why the research is weak.

Reviewed by: William Maish, MD MBA MPH, Clinical Product Lead
Published: October 5, 2026
Last updated: October 5, 2026

Key takeaway

PN-943 is an investigational oral peptide that blocks the α4β7 integrin, the same gut-homing target as the antibody vedolizumab, developed by Protagonist Therapeutics for ulcerative colitis. Its earliest controlled trial missed its primary endpoint, and a later Phase 2 reported only a partial, internally inconsistent signal. As of 2026 it is not approved and the program is inactive.

At a glance

FDA status	Investigational peptide, not approved by the FDA
What it is	Oral α4β7 integrin antagonist studied for ulcerative colitis
Research	First controlled trial missed its primary endpoint
Development status	Later Phase 2 showed a mixed signal, and the program is inactive
Evidence strength	Low research

What is PN-943?

PN-943 is an experimental peptide taken by mouth, designed to act locally in the gut, developed by Protagonist Therapeutics for moderate-to-severe ulcerative colitis, an inflammatory bowel disease. It blocks the α4β7 integrin, the same pathway targeted by the approved injectable antibody vedolizumab, but as an oral peptide. It is investigational and not approved.

How does it work?

PN-943 blocks the α4β7 integrin¹ on immune cells (lymphocytes), preventing it from binding its partner MAdCAM-1 on blood vessels in the gut. That interaction is how certain inflammatory T-cells "home" to the intestinal lining, so blocking it is intended to reduce the gut inflammation that drives ulcerative colitis. Delivering this as a gut-targeted oral peptide is the distinguishing idea. This describes the mechanism, separate from the trial outcomes below.

Is it FDA-approved?

No. PN-943 is investigational and not approved. According to company disclosures, after its Phase 2 readout:

Protagonist indicated the drug would need an external partner to advance
No Phase 3 has started
The company's focus shifted to other programs

What does the research show?

The controlled evidence is weak, as the two trials show:

Trial	Source	Result
Earlier Phase 2a study of the molecule, then called PTG-100	Peer-reviewed, indexed on PubMed	Missed¹ its pre-specified primary endpoint; a positive signal appeared only on a blinded re-read of endoscopy images at lower doses
Subsequent Phase 2 IDEAL trial	Company-reported, not peer-reviewed	Remission signal at the lower dose but not the higher dose, an inconsistent dose-response

No Phase 3 has advanced, so efficacy is not established.

More for digestive & weight

Sources: the Phase 2a trial of the molecule as PTG-100 (Sandborn et al., Gastroenterology, 2021, DOI: 10.1053/j.gastro.2021.08.045¹), indexed on PubMed; and Protagonist Therapeutics disclosures of the Phase 2 IDEAL results. This document is educational, is not medical advice or a health claim, and is not an offer to sell any product.