Oral peptide with biologics-like high potency and spectrum of activity against three therapeutically relevant dimeric forms of IL-17 (AA, AF and FF)

IND enabling studies underway, with Phase I initiation expected in Q425

Webcast and conference call to be held today at 4:30 pm ET

NEWARK, CA / ACCESSWIRE / November 21, 2024 / Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") today announced the selection of PN-881, a potential best-in-class oral peptide interleukin-17 (IL-17) antagonist, as a development candidate for the treatment of immune-mediated skin diseases.

"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 analog, and better than, or on par with, various approved or developmental stage injectable antibody or nanobody therapeutic agents," said Dinesh V. Patel, PhD, President and CEO of Protagonist. "PN-881 is another example of our expertise with discovery and development of oral peptides. Earlier this week, we and our partner announced the successful outcome in two separate Phase 3 psoriasis studies with the oral peptide IL-23 receptor antagonist icotrokinra."

PN-881 has completed extensive 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 7-day and 3-month toxicology studies. Planned clinical studies include a Phase 1 single ascending dose (SAD) and multiple ascending dose (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.

"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," added Dr. Patel. "We look forward to progressing PN-881 rapidly into a first-in-human Phase 1 study in Q4 2025."

Conference Call and Webcast Details
The dial-in numbers for Protagonist's investor update on Thursday, November 21st at 4:30 pm ET are:

The webcast link for the event can be found here: https://viavid.webcasts.com/starthere.jsp?ei=1698744&tp_key=f6482f31c0

A replay of the presentation will be available on the Company's Investor Relations Events and Presentations webpage following the event.

About Protagonist

Protagonist Therapeutics is a late-stage development biopharmaceutical company. Two novel peptides derived from Protagonist's proprietary discovery platform are currently in advanced Phase 3 clinical development, with New Drug Application submissions to the FDA potentially in 2025. Icotrokinra (JNJ-2113, formerly PN-235), is the first targeted oral peptide designed to selectively block the IL-23 receptor,which underpins the inflammatory response in moderate-to-severe plaque PsO and other IL-23-mediated diseases. Icotrokinra binds to the IL-23 receptor with single-digit picomolar affinity and demonstrated potent, selective inhibition of IL-23 signaling in human T cells. Icotrokinra is licensed to Johnson & Johnson (JNJ) and is currently in Phase 3 development for psoriasis and is nearing completion of Phase 2b development for ulcerative colitis. Following icotrokinra's joint discovery by Protagonist and JNJ scientists pursuant to the companies' IL-23R collaboration, Protagonist was primarily responsible for development of icotrokinra through Phase 1, with JNJ assuming responsibility for development in Phase 2 and beyond. Rusfertide, a mimetic of the natural hormone hepcidin, is currently in Phase 3 development for the rare blood disorder polycythemia vera. Rusfertide is being co-developed and will be co-commercialized with Takeda Pharmaceuticals pursuant to a worldwide collaboration and license agreement entered into in 2024 under which the Company remains primarily responsible for development through NDA filing. The Company also has a number of pre-clinical stage oral drug discovery programs addressing clinically and commercially validated targets, including IL-17 blocker PN-881, hepcidin mimetic, and anti-obesity programs.

More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company's website at https://www.protagonist-inc.com/.

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the potential benefits of PN-881, the potential market for PN-881, and the timing of PN-881 development. In some cases, you can identify these statements by forward-looking words such as "anticipate," "believe," "may," "will," "expect," or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, our ability to earn milestone payments under our collaboration agreements with Janssen and Takeda, our ability to use and expand our programs to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, and our ability to obtain and adequately protect intellectual property rights for our product candidates. Additional information concerning these and other risk factors affecting our business can be found in our periodic filings with the Securities and Exchange Commission, including under the heading "Risk Factors" contained in our most recently filed periodic reports on Form 10-K and Form 10-Q filed with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release.

Investor Relations Contact
Corey Davis, Ph.D.
LifeSci Advisors
cdavis@lifesciadvisors.com
+1 212 915 2577

Media Relations Contact
Virginia Amann
ENTENTE Network of Companies
virginiaamann@ententeinc.com
+1 833 500 0061

SOURCE: Protagonist Therapeutics