JNJ-2113 achieved all primary and secondary endpoints in the Phase 2b clinical trial FRONTIER 1, including PASI 100 and IGA 0 responses of 40.5 percent and 45.2 percent, respectively.

NEWARK, CA / ACCESSWIRE / February 7, 2024 / Protagonist Therapeutics, Inc. (NASDAQ:PTGX) ("Protagonist" or the "Company") today announced publication in the New England Journal of Medicine (NEJM) of the Phase 2b FRONTIER 1 trial evaluating JNJ-2113 in adults living with moderate-to-severe plaque psoriasis (PsO). The publication will be accessible at www.nejm.org.

JNJ-2113 is the first- and only-in-class targeted oral peptide inhibitor of the IL-23 receptor in clinical development. Based on the robust efficacy observed in moderate to severe PsO described in this NEJM publication, JNJ-2113 is currently being evaluated in multiple Phase 3 psoriasis studies in the ICONIC-program. PASI-90 is one of the co-primary endpoints for the initiated ICONIC-LEAD and the planned ICONIC-ADVANCE 1 and 2 Phase 3 studies, reflecting a higher bar for treatment goals in moderate to severe psoriasis. In addition, a Phase-2b ANTHEM-UC study with JNJ-2113 in ulcerative colitis is also currently in progress.

This manuscript presented data from a randomized, multicenter, double-blind, placebo-controlled clinical trial, the FRONTIER 1 Phase 2b trial (NCT05223868) which evaluated three once-daily dosages and two twice-daily dosages of the oral targeted therapy peptide JNJ-2113. It was designed to assess the efficacy and safety of JNJ-2113 in patients with moderate-to-severe plaque PsO. A total of 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], and 100 mg twice daily [n=42]). The trial included a four-week screening period, a 16-week treatment period and a four-week safety follow-up period.

The primary endpoint of FRONTIER 1 was a reduction from baseline of at least 75% in the Psoriasis Area and Severity Index score (PASI-75 response) at Week 16. Study results showed a dose ordered-response in patients treated with JNJ-2113 on PASI-75 at Week 16, compared to patients treated with placebo, with 79 percent of patients achieving a PASI-75 response in the highest dose group tested of 100 mg twice daily. Results from secondary endpoints were consistent with these data, with the highest dose of JNJ-2113 showing 59.5% of patients achieving PASI-90, and 40.5% of patients achieving a PASI-100 at Week 16.

Additionally, a greater proportion of adult patients who received JNJ-2113 achieved an Investigator's Global Assessment (IGA) of cleared/minimal skin lesions (score of 0/1, respectively) at Week 16 versus patients treated with placebo. At the highest JNJ-2113 dose, 64.3% of patients achieved an IGA score of 0/1 and 45.2% of patients achieved a score of 0. IGA response rates showed a separation between JNJ-2113 and placebo groups as early as Week 4 and increased through Week 16.

In the study, improvements were observed across key Patient-Reported Outcomes (PROs) as measured by the Psoriasis Symptoms and Signs Diary (PSSD) and the Dermatology Life Quality Index (DLQI) among adult patients who received JNJ-2113. JNJ-2113-treated patients demonstrated greater improvements from baseline in the severity of their symptoms by Week 16, as assessed by the PSSD. Among patients with baseline DLQI scores greater than 1, significantly higher proportions of JNJ-2113-treated patients compared with placebo-treated patients achieved DLQI scores of 0/1 (no impact on quality of life) at Week 16.

Treatment with JNJ-2113 was associated with lower serum levels of human beta-defensin 2 (hBD-2), relative to placebo, as early as Week 4. The lowest hBD-2 level was observed with the 100 mg twice-daily dose, beginning by Week 8. Serum hBD-2 can be a useful biomarker of disease activity in people living with moderate-to-severe plaque PsO, as lower levels correlate with clinical response and indicate inhibition of the IL-17/IL-23 axis. The proportion of patients with adverse events (AEs) was comparable between the JNJ-2113 and placebo groups.

"We are extremely pleased with the clinical success thus far with our first- and only-in-class oral IL-23 receptor antagonist JNJ-2113 in psoriasis," said Dinesh V. Patel, Ph.D., President and CEO of Protagonist. "The strength of the FRONTIER 1 Phase 2b data and the robust ICONIC clinical program involving four different Phase 3 psoriasis studies, gives us ongoing confidence in JNJ-2113 and its future potential to address unmet needs in psoriasis and other IL-23 pathway mediated diseases including psoriatic arthritis, Crohn's disease and ulcerative colitis. A Phase 2b study with JNJ-2113 is currently in progress. The success of JNJ-2113 and our oral peptide based targeted therapy approach has also encouraged us to evaluate other biological targets besides IL-23 in the inflammatory and immunomodulatory space."

"Plaque psoriasis affects an estimated eight million Americans and more than 125 million people worldwide. Nearly one-quarter of the cases are considered moderate-to-severe and significantly impact daily life," said Scott Plevy, M.D., Executive Vice President and Therapeutic Head, Gastroenterology of Protagonist. "The significant improvement in clinical and patient-reported outcomes reported in the NEJM article with a favorable safety profile is very encouraging, and we look forward to future data readouts from both the Phase 3 psoriasis ICONIC program and the ANTHEM-UC Phase 2b ulcerative colitis study."

About JNJ-2113

JNJ-2113 is a first and only targeted oral peptide that is designed to selectively block the IL-23 receptor that was jointly discovered and is being developed pursuant to the license and collaboration agreement between Protagonist and Janssen. Protagonist completed a Phase 1 study of JNJ-2113 in 2021 and Johnson & Johnson retains exclusive, worldwide rights to develop in Phase 2 and beyond, and to commercialize compounds derived from the research conducted pursuant to the agreement which covers a broad range of indications.

The pivotal Phase 3 ICONIC clinical development program of JNJ-2113 in adult and adolescent patients with moderate-to-severe plaque PsO was initiated with two studies in Q4 2023 - ICONIC-LEAD and ICONIC-TOTAL. ICONIC-LEAD is a randomized controlled trial (RCT) to evaluate the safety and efficacy of JNJ-2113 compared with placebo in participants with moderate-to-severe plaque PsO, with the higher efficacy bar set with the co-primary endpoints of PASI-90 and IGA score of 0 or 1 with at least a 2-grade improvement. ICONIC-TOTAL is a RCT to evaluate the efficacy and safety of JNJ-2113 compared with placebo for the treatment of PsO in participants with at least moderate severity affecting special areas (e.g., scalp, genital, and/or palms of the hands and the soles of the feet) with overall IGA score of 0 or 1 with at least a 2-grade improvement as the primary endpoint. Other Phase 3 studies in the development program are expected to begin in Q1 2024, including ICONIC ADVANCE 1 and ICONIC ADVANCE 2, which will evaluate the safety and efficacy of JNJ-2113 compared with both placebo and deucravacitinib.

A Phase 2b study, ANTHEM-UC, has been initiated, to evaluate the safety and effectiveness of JNJ-2113 compared with placebo in participants with moderately to severely active ulcerative colitis. JNJ-2113 is currently being studied in the ICONIC program, which includes four Phase 3 studies for moderate-to-severe psoriasis. Details regarding ANTHEM-UC and the ICONIC Phase 3 psoriasis trials can be found on clinicaltrials.gov.

About Protagonist

Protagonist Therapeutics is a biopharmaceutical company with peptide-based new chemical entities (NCEs) 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 Interleukin-23 receptor (IL-23R) collaboration with Johnson & Johnson and followed it through IND-enabling pre-clinical and Phase 1 studies, with Johnson & Johnson 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 development program. The randomized portion of the Phase 2 REVIVE study was unblinded, showing positive results and is now complete, with an open-label extension underway. The global Phase 3 VERIFY study of rusfertide in polycythemia vera is ongoing. Rusfertide is being co-developed and co-commercialized by Protagtonist and Takeda Pharmaceuticals Co Ltd.

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 Johnson & Johnson. 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 Johnson & Johnson, 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.

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SOURCE: Protagonist Therapeutics, Inc.