A novel oral peptide PN-477o with once-daily dosing, high potency and activation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon (GCG) receptors

Company will also develop a subcutaneous version, PN-477sc, as a once-weekly injection

IND-enabling studies underway, with Phase I study initiation expected in 2Q26

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

NEWARK, CALIFORNIA / ACCESS Newswire / June 30, 2025 / Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") today announced the selection of PN-477, a potential best-in-class GLP-1, GIP, GCG receptor triple agonist peptide with oral and subcutaneous routes of administration, as a development candidate for the treatment of obesity. The triple agonist PN-477 is designed to offer the optimal combination of total body weight loss, improved gastrointestinal (GI) tolerability and fat to lean mass ratio, with the dosing convenience of a once-daily oral agent and the added optionality of a once-weekly subcutaneous administration.

"We are very pleased to nominate development candidate PN-477, a promising potential best-in class oral GLP-1, GIP, GCG receptor tri-agonist peptide which has demonstrated optimal absolute and relative activity against all three hormone receptors in preclinical testing," said Dinesh V. Patel, PhD, President and CEO of Protagonist. "PN-477 is specifically engineered to be orally stable with attention to the relative balance of potencies against the three receptors to potentially leverage their beneficial effects on weight loss and optimal body composition while mitigating their adverse effects. As with our previous drug candidates and late-stage assets, PN-477 is a testament to the power of our peptide technology platform, including the ability to deliver first- and best-in-class targeted oral and injectable peptide therapeutics."

PN-477 has completed extensive preclinical evaluation including oral and metabolic stability, potency, pharmacokinetics and pharmacodynamics studies, and has demonstrated effects in preclinical models of obesity and glycemic control. PN-477 has shown potent in vitro activity in activating the GLP-1, GIP, and GCG receptors. PN-477 also demonstrated robust preclinical proof-of-concept in various animal studies including the diet induced obesity (DIO) preclinical mouse model, normal dogs, and cynomolgus monkeys. Overall, PN-477 has the right balance of potency, oral and in-vivo stability, and pharmacokinetic properties to enable parallel development both as a once-daily oral (PN-477o) and once-weekly injectable (PN-477sc) treatment options. IND enabling studies of PN-477 are underway and initiation of Phase 1 clinical studies is anticipated in the second quarter of 2026.

"While GLP-1 agonists have dominated the market thus far, there remains a broad opportunity for novel therapeutics with better body weight loss, higher ratio of fat to lean mass loss, tolerability and additional beneficial effects in obesity-related comorbidities. A triple GLP-1, GIP, GCG receptor agonist peptide that offers weight loss on par with the best injectable treatments options, as well as the optionality provided by both oral and injectable routes of administration, would be an important therapeutic breakthrough and represents another potential blockbuster drug opportunity for Protagonist," added Dr. Patel. "We look forward to moving PN-477 into first-in human clinical Phase 1 studies in the second quarter of 2026."

Conference Call and Webcast Details
The dial-in numbers for Protagonist's investor update on Monday, June 30^th at 4:30 pm ET are:

US-based Investors: 1-877-407-0752
International Investors: 1-201-389-0912
Conference Call ID: 13754335

The webcast link for the event can be found here: https://viavid.webcasts.com/starthere.jsp?ei=1724439&tp_key=584cdd1e86

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 discovery through 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 (formerly, JNJ-2113) is a first-in-class investigational targeted oral peptide that selectively blocks the Interleukin-23 receptor ("IL-23R") which is licensed to J&J Innovative Medicines ("JNJ"), formerly Janssen Biotech, Inc. 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 (PV). Rusfertide is being co-developed and will be co-commercialized with Takeda Pharmaceuticals pursuant to a worldwide collaboration and license agreement entered in 2024 under which the Company remains primarily responsible for development through NDA filing. The Company also has a number of pre-clinical stage drug discovery programs addressing clinically and commercially validated targets, including IL-17 oral peptide antagonist PN-881, obesity triple agonist peptide PN-477, and oral hepcidin.

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-477, and the timing of PN-477 clinical 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 ext. 1

SOURCE: Protagonist Therapeutics