Protagonist Therapeutics selects PN-881 as development candidate

Protagonist Therapeutics (PTGX) announced the selection of PN-881, an oral peptide interleukin-17, or IL-17, antagonist, as a development candidate for the treatment of immune-mediated skin diseases. PN-881 has completed preclinical studies, including oral stability, potency, tissue distribution, and pharmacokinetics measurements, and evaluation in immunologic pharmacodynamics and preclinical efficacy models. PN-881 has demonstrated in vitro blockade of IL-17 AA homodimer, FF homodimer and AF heterodimer. It has shown approximately 100-fold greater potency than secukinumab, and similar potency to the most potent approved antibody drugs and nanobody therapeutics in development. In multiple preclinical studies with oral dosing, PN-881 showed effective blockade in vivo of IL-17 in serum and skin and achieved preclinical proof-of-concept in a skin inflammation rodent disease model. IND enabling studies of PN-881 are ongoing, including seven-day and three-month toxicology studies. Planned clinical studies include a Phase 1 single ascending dose, or SAD, and multiple ascending dose, or MAD, study expected to begin in the fourth quarter of 2025. Results of the Phase 1 trial will inform the design and dosing in a subsequent dose-ranging psoriasis trial. Rapid expansion into other IL-17 mediated diseases, including psoriatic arthritis, hidradenitis suppurativa, and axial spondyloarthropathies, will be based on results observed in psoriasis studies.