Protagonist Advances PN-881 A Top-Notch Antagonist For Immune-Mediated Skin Disease Treatment
Protagonist announces PN-881, an oral IL-17 antagonist with preclinical success, targeting skin conditions.
Breaking News
Nov 22, 2024
Simantini Singh Deo

Protagonist Therapeutics, Inc. has announced PN-881 as its latest development candidate, targeting immune-mediated skin conditions with a potentially best-in-class oral peptide interleukin-17 (IL-17) antagonist. This candidate has undergone extensive preclinical testing, including studies on oral stability, potency, tissue distribution, pharmacokinetics, and immunologic pharmacodynamics. It has also demonstrated preclinical efficacy in rodent models of skin inflammation.
In lab studies, PN-881 effectively blocked IL-17 AA and FF homodimers and the AF heterodimer, showing approximately 100 times the potency of secukinumab and comparable effectiveness to leading approved antibody drugs and nanobody therapies. Preclinical oral dosing confirmed its ability to block IL-17 activity in serum and skin, achieving proof-of-concept for its therapeutic potential.
The candidate is undergoing IND-enabling toxicology studies, including 7-day and 3-month evaluations. A Phase 1 clinical trial featuring single and multiple ascending dose studies will begin in late 2025. Results from this trial will guide dosage and design for a follow-up psoriasis study. Based on findings from psoriasis research, Protagonist plans to expand PN-881's development into other IL-17-driven conditions, such as psoriatic arthritis, hidradenitis suppurativa, and axial spondyloarthropathies.
Dinesh V. Patel, PhD, President and CEO of Protagonist, said in a statement, "We are extremely pleased to nominate development candidate PN-881, a promising potential best-in-class oral peptide IL-17 antagonist that has demonstrated robust activity against all three therapeutically relevant dimeric forms of the IL-17 ligand in preclinical testing. The potency of PN-881 in our testing is orders of magnitude better than an anti-IL-17 oral small molecule analogue, and better than, or on par with, various approved or developmental stage injectable antibodies or nanobody therapeutic agents."
Dr Patel also commented, "PN-881 is another example of our expertise with the discovery and development of oral peptides. Earlier this week, we and our partner announced the successful outcome of two separate Phase 3 psoriasis studies with the oral peptide IL-23 receptor antagonist icotrokinra. IL-17 and IL-23 blockers are collectively expected to lead the dermatology market, with broad opportunity for multiple indications in addition to psoriasis. An IL-17 antagonist peptide like PN-881, with best-in-class potential as an oral targeted therapy, offers an attractive therapeutic option for patients and represents another potential blockbuster drug opportunity for Protagonist.
We look forward to progressing PN-881 rapidly into a first-in-human Phase 1 study in Q4 2025."