Protagonist Therapeutics Announces Positive Topline Results with JNJ-2113, the First and Only Oral IL-23 Receptor Antagonist Peptide in Development for Moderate-to-Severe Plaque Psoriasis

Phase 2b FRONTIER 1 data presentation at World Congress of Dermatology highlights that a greater proportion of patients achieved 75, 90 and 100 percent improvement in skin clearance at week 16 in comparison to placebo

Phase 3 development in moderate-to-severe plaque psoriasis and Phase 2b development in ulcerative colitis are planned by Janssen

NEWARK, CA / ACCESSWIRE / July 4, 2023 / Protagonist Therapeutics, Inc. ("Protagonist" or "the Company") today announced positive topline results from the Phase 2b FRONTIER 1 clinical trial evaluating the oral interleukin-23 receptor (IL-23R) antagonist JNJ-2113 (formerly PN-235) in adult patients with moderate-to-severe plaque psoriasis (PsO)[i] presented at World Congress of Dermatology in Singapore. The trial achieved all primary and secondary efficacy endpoints. JNJ-2113 is being developed by Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), under Protagonist's license and collaboration agreement with Janssen.

A greater proportion of patients who received JNJ-2113 achieved PASI 75 (primary endpoint) as well as PASI 90 and PASI 100 (75, 90, and 100 percent improvement in skin lesions as measured by the Psoriasis Area and Severity Index, respectively) compared to placebo, at week 16.ⁱ Trial results for JNJ-2113 demonstrated a profilei that supports its advancement into Phase 3 clinical development for moderate-to-severe plaque PsO in adult patients.

A summary of data from the FRONTIER 1 study is as follows:

Treatment was generally well tolerated, and the proportions of patients with adverse events were comparable between patient groups.i The proportion of participants experiencing one or more adverse events (AEs) was 52.4 percent (n=111) in the combined JNJ-2113 group and 51.2 percent (n=52) in the placebo group.i Although there was variability across the treatment groups, there was no evidence of a dose-dependent increase in the occurrence of specific AEs across the JNJ-2113 treatment groups.i

"As the first and only oral IL-23 receptor antagonist with the Phase 2b FRONTIER trial results suggesting the potential for being the best-in-class oral agent for psoriasis, we believe that JNJ-2113, formerly PN-235, can have a transformative impact on the treatment paradigm of psoriasis and additional IL-23-mediated diseases, improving the range of treatment options available to patients around the world," said Dinesh V. Patel, PhD, President and CEO of Protagonist. "The positive results from the FRONTIER 1 study underscore the strength of Protagonist's proprietary peptide technology platform, the world-class capabilities of its discovery and development teams, and the success of our Company's six-plus-year collaboration with Janssen."

"For Protagonist," Dr. Patel continued, "the impressive trajectory that started with our peptide technology platform, which in turn led to our collaboration with Janssen and the eventual discovery and development of JNJ-2113, to today's announcement of a planned pivotal Phase 3 program in psoriasis and a Phase 2b study in ulcerative colitis, is a great reflection of our expertise in the field of oral peptides and our ability to work effectively and deliver results in partnerships. Independently, Protagonist continues to utilize its technology platform and know-how to innovate novel oral assets against other biological targets and diseases in which an oral approach can offer significant differentiation and superiority in addressing major unmet medical needs."

About FRONTIER 1 (NCT05223868)

The FRONTIER 1 Phase 2b trial (NCT05223868) is a randomized, multicenter, double-blind, placebo-controlled clinical trial that evaluated three once-daily dosages and two twice-daily dosages of JNJ-2113 taken orally.i^,vii It was designed to assess the efficacy and safety of JNJ-2113 in patients with moderate-to-severe plaque PsO.i 255 participants were randomized into six treatment groups (placebo [n=43], 25 mg daily [n=43], 25 mg twice daily [n=41], 50 mg daily [n=43], 100 mg daily [n=43], 100 mg twice daily [n=43]).ⁱ The total duration of the trial was up to 24 weeks which included a screening period of less than or equal to four weeks, a 16-week treatment period, and a four-week safety follow-up period.i

The primary endpoint of the clinical trial was the proportion of patients achieving PASI 75 at 16 weeks.i Secondary endpoints include change from baseline in PASI total score at week 16, percentage of participants achieving PASI 90 and PASI 100 score at week 16, percentage of participants achieving an Investigator's Global Assessment (IGA) score of cleared (0) or minimal (1) at week 16, change from baseline in body surface area (BSA) at week 16, change from baseline in Psoriasis Symptoms and Signs Diary (PSSD) symptoms scores at week 16, percentage of participants achieving PSSD symptoms score=0 at week 16 in participants with a baseline symptoms score >=1, percentage of participants achieving a Dermatology Life Quality Index (DLQI) of 0 or 1 at week 16 in participants with baseline DLQI Score >1, change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS-29) domain score at week 16, percentage of participants who achieve >= 5-point improvement from baseline in PROMIS-29 domain score at week 16, and number of participants with adverse events and serious adverse events up to 24 weeks.vii

About JNJ-2113

JNJ-2113 (formerly PN-235) is a novel oral IL-23R antagonist peptide which binds with high affinity to the IL-23 receptor and has properties that allow it to be absorbed[ii] with oral dosing.[iii] JNJ-2113 selectively and potently blocks IL-23 signaling and downstream inflammatory cytokine production.ii^,[iv]

The IL-23/IL-23R signaling pathway plays a critical role in the pathogenesis of immune-mediated inflammatory diseases, including psoriasis, psoriatic arthritis, and inflammatory bowel diseases.[v]^,[vi]

Protagonist-Janssen Collaboration

JNJ-2113 was discovered using Protagonist's proprietary peptide discovery platform and is being developed pursuant to Protagonist's license and collaboration agreement with Janssen. The initial collaboration agreement was established in 2017[vii]^,[viii]. The agreement was amended in 2019 to provide for a research collaboration pursuant to which Janssen provided financial support for Protagonist research FTEs to pursue second-generation compounds and to add milestones for those compounds. JNJ-2113 was one of the second-generation compounds discovered in this collaboration and nominated by Janssen for further development under the amended agreement. The agreement was further amended in 2021 to restructure development milestones, expand Janssen's research rights, and limit Protagonist's cost sharing obligations to studies that have since been completed.

Protagonist completed pre-clinical and phase 1 studies of JNJ-2113, after which Janssen assumed responsibility for all further development. Janssen has exclusive, worldwide rights to develop JNJ-2113 in Phase 2 clinical trials and beyond, and to commercialize compounds derived from the research conducted pursuant to the agreement against a broad range of indications.[ix]

Advancement of JNJ-2113 into a Phase 3 study in psoriasis and meeting the primary endpoint in that study qualifies Protagonist for milestone payments of $50 million and $115 million, respectively. A Phase 2 study initiation in a second indication qualifies the Company for a $10 million milestone. In total, Protagonist remains eligible for up to $855 million in various future milestone payments, as well as upward tiering royalties based on worldwide net sales.

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. Protagonist scientists jointly discovered PN-235 (now known as JNJ-2113) as part of Protagonist's IL-23R collaboration with Janssen and followed it through IND-enabling pre-clinical and Phase 1 studies, with Janssen assuming responsibility for further clinical development. 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 Phase 2 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.

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 the potential benefits of JNJ-2113, our expectations regarding the clinical development of JNJ-2113 and our potential receipt of milestone and royalty payments under our collaboration agreement with Janssen Biotech, Inc. 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 agreement with Janssen Biotech, Inc. the impact of the current COVID-19 pandemic on our discovery and development efforts, 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.

Contact
Jami Taylor
Email: [email protected]

[i] Bissonnette R, Pinter A, Ferris L, et al. Data Presentation. A Phase 2, Randomized, Placebo-controlled, Dose-ranging Study of Oral JNJ-77242113 for the Treatment of Moderate-to-Severe Plaque Psoriasis: FRONTIER 1. Presented at WCD 2023, July 3-8.

[ii] Fourie A, et al. First-In-Class Oral Peptide Systemically Targeting the Il-23 Pathway. Presented at ISID 2023, May 10-13. Available at: https://irp.cdn-website.com/8e9b9820/files/uploaded/ISID%202023_Fourie%20(JNJ77242113%20Concurrent)_final.pdf. Accessed June 2023.

[iii] Dougherty PG, et al. Understanding Cell Penetration of Cyclic Peptides. Chem Rev. 2019 Sep 11; 119(17): 10241-10287.

[iv] Protagonist Therapeutics. Press Release. Protagonist Reports Positive Results from Phase 1 and Pre-clinical Studies of Oral Interleukin-23 Receptor Antagonist JNJ-2113. Available at: https://www.prnewswire.com/news-releases/protagonist-reports-positive-results-from-phase-1-and-pre-clinical-studies-of-oral-interleukin-23-receptor-antagonist-jnj-2113-301823039.html. Accessed June 2023.

[v] Razawy W, et al. The role of IL‐23 receptor signaling in inflammation‐mediated erosive autoimmune arthritis and bone remodeling. Eur J Immunol. 2018 Feb; 48(2): 220-229.

[vi] Tang C, et al. Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology. 2012 Feb; 135(2): 112-124.

[vii] Protagonist Therapeutics. Press Release. Protagonist Therapeutics Announces Positive Topline Results for Phase 2b FRONTIER 1 Clinical Trial of Oral IL-23 Receptor Antagonist JNJ-2113 (PN-235) in Psoriasis. Available at: https://www.prnewswire.com/news-releases/protagonist-therapeutics-announces-positive-topline-results-for-phase-2b-frontier-1-clinical-trial-of-oral-il-23-receptor-antagonist-jnj-2113-pn-235-in-psoriasis-301764181.htmlhttps://www.prnewswire.com/news-releases/protagonist-therapeutics-announces-positive-topline-results-for-phase-2b-frontier-1-clinical-trial-of-oral-il-23-receptor-antagonist-jnj-2113-pn-235-in-psoriasis-301764181.html. Accessed June 2023.

[viii] Johnson & Johnson. Press Release. Janssen Enters Into Worldwide Exclusive License and Collaboration Agreement With Protagonist Therapeutics, Inc. For The Oral Interlukin-23 Receptor Antagonist Drug Candidate For The Treatment of Inflammatory Bowel Disease. Available at: https://www.jnj.com/media-center/press-releases/janssen-enters-into-worldwide-exclusive-license-and-collaboration-agreement-with-protagonist-therapeutics-inc-for-the-oral-interlukin-23-receptor-antagonist-drug-candidate-for-the-treatment-of-inflammatory-bowel-disease. Accessed June 2023.

[ix] Protagonist Therapeutics. Press Release. Protagonist Therapeutics Announces Amendment of Agreement with Janssen Biotech for the Continued Development and Commercialization of IL-23 Antagonists. Available at: https://www.prnewswire.com/news-releases/protagonist-therapeutics-announces-amendment-of-agreement-with-janssen-biotech-for-the-continued-development-and-commercialization-of-il-23-antagonists-301343621.html. Accessed June 2023.

SOURCE: Protagonist Therapeutics, Inc.