Protagonist Reports Positive Results from Phase 1 and Pre-clinical Studies of Oral Interleukin-23 Receptor Antagonist JNJ-2113

Data point to the potential of JNJ-2113 as a first-in-class drug candidate in multiple IL-23 driven-diseases

NEWARK, Calif., May 12, 2023 /PRNewswire/ -- Protagonist Therapeutics (Nasdaq: PTGX) ("Protagonist" or "the Company") reported data from its collaboration with Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), on Phase 1 and preclinical studies of JNJ-2113 (formerly PN-235), presented by Janssen and co-authored with Protagonist, as an oral presentation at the International Societies for Investigative Dermatology (ISID) 2023 meeting in Tokyo, Japan. The presentation, "First-in-class oral peptide systemically targeting the IL-23 pathway," is available online at isid2023.org for registered users.

Highlights of the data presented on JNJ-2113 include the following:

• JNJ-2113 is a macrocyclic peptide that binds to the IL-23 receptor with single digit picomolar affinity and demonstrated potent, selective inhibition of IL-23 signaling in human T cells.
• Although peptides typically have low oral bioavailability, the high potency of JNJ-2113, along with its oral stability, indicated potential for systemic activity beyond the gastrointestinal tract in rat models of inflammation and colitis.
• In a rat trinitrobenzene sulfonic acid (TNBS)-induced colitis model, efficacy was observed as measured by attenuation of weight loss and colon inflammation with oral doses of JNJ-2113 as low as 0.3 mg/kg/day.
• In an IL-23-induced rat skin inflammation model, orally dosed JNJ-2113 achieved inhibition of inflammation equivalent to an IL-23 antibody, along with reduction of IL-17 and IL-22 cytokines.
• Oral treatment with JNJ-2113 provided selective systemic IL-23 pathway inhibition in pre-clinical models that successfully translated to systemic pharmacodynamics activity in healthy human volunteers, indicating potential for JNJ-2113 as a first-in-class oral therapy targeting IL-23-mediated diseases.

"JNJ-2113 is a potential first-in-class drug candidate in multiple aspects, such as with respect to its biological target, the IL-23 receptor; its oral mode of drug delivery; and its chemical modality as a peptide, representing a major breakthrough in the field of innovative oral peptide-based therapeutics," said Dinesh V. Patel, Ph.D., President and CEO of Protagonist. "These data demonstrated pre-clinical proof-of-concept in skin inflammation and colitis disease models, highlighting JNJ-2113's potential for therapeutic utility in both psoriasis and inflammatory bowel diseases implicated in the IL-23 pathway. We look forward to the presentation of the Phase 2b FRONTIER 1 study data in adults with moderate-to-severe plaque psoriasis later this year."

About Protagonist

Protagonist Therapeutics is a biopharmaceutical company with peptide-based new chemical entities rusfertide and JNJ-2113 (formerly PN-235) in advanced stages of clinical development, both derived from the Company's proprietary technology platform. Rusfertide, a mimetic of the natural hormone hepcidin, is the Company's lead drug candidate currently in a global Phase 3 stage of development. The REVIVE study is now complete, with an open-label extension underway. The global Phase 3 VERIFY study of rusfertide in polycythemia vera is ongoing. Protagonist retains all worldwide development and commercialization rights to rusfertide.

Positive topline results from the FRONTIER 1 study of JNJ-2113 in moderate-to-severe plaque psoriasis became available in March 2023, with further details to be shared at medical meetings starting in the second quarter of 2023. Advancement of JNJ-2113 into a Phase 3 study and meeting the primary endpoint in that study would qualify Protagonist for milestone payments of $50 million and $115 million, respectively. In total, Protagonist remains eligible for up to $855 million in various milestone payments and tiered royalties based on worldwide net drug sales.

More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company's website at 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 our intentions or current expectations concerning, among other things, our expectations regarding the potential benefits and therapeutic utility of JNJ-2113. 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, delays or difficulties in enrolling or completing clinical studies, the potential that results from clinical or non-clinical studies indicate our compounds or product candidates are unsafe or ineffective, dependence on third parties to conduct clinical studies and manufacture our products, our ability to earn milestone payments under our collaboration agreement with Janssen Biotech, the impact of the current COVID-19 pandemic on our discovery and development efforts, impact of natural disasters and the impact of the ongoing military conflict in Ukraine and Russia on any future studies, 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.

SOURCE Protagonist Therapeutics, Inc.