Long-term extension (LTE) FRONTIER 2 study demonstrated sustained efficacy and similar safety results from Week 16 to Week 52, consistent with previously reported FRONTIER 1 16-week Phase 2b study

The proportion of patients achieving PASI 75, 90 and 100 response rates at Week 16 were maintained through Week 52, confirming the durability of response

59.5% and 64.3% of patients in the highest dose group (100 mg BID) achieved a PASI 90 response at Weeks 16 and 52 respectively; PASI 90 is a co-primary endpoint for multiple Phase 3 studies in the ICONIC clinical development program

No evidence of dose-dependent increase in AEs across the JNJ-2113 treatment groups

NEWARK, CA / ACCESSWIRE / March 11, 2024 / Protagonist Therapeutics, Inc. ("Protagonist" or "the Company") today announced a late-breaking presentation at the American Academy of Dermatology (AAD) 2024 Annual Meeting with positive results from the Phase 2b FRONTIER 2 long-term extension study evaluating JNJ-2113, the first and only investigational targeted oral peptide designed to block the IL-23 receptor, for adult patients with moderate-to-severe plaque psoriasis (PsO). JNJ-2113 is being developed by J&J Innovative Medicine, Inc. (see today's accompanying press release from J&J), under a license and collaboration agreement with Protagonist, and is currently enrolling four pivotal Phase 3 psoriasis studies in the ICONIC clinical development program and one Phase 2b ulcerative colitis study.

FRONTIER 2 enrolled patients who completed the 16-week dose ranging FRONTIER 1 Phase 2b study and evaluated patients from Week 17 through Week 52. In FRONTIER 2, JNJ-2113 maintained high rates of skin clearance through 52 weeks in adults with moderate-to-severe plaque psoriasis, as measured by Psoriasis Area and Severity Index (PASI) response rates of 75%, 90% and 100%. Recently, results from FRONTIER 1 were published in The New England Journal of Medicine and showed superior efficacy of JNJ-2113 at all doses tested and similar safety compared to placebo at Week 16.

"The positive and consistent results from the 52-week FRONTIER 2 study demonstrate the durability of response observed in the 16-week FRONTIER 1 study and reaffirm JNJ-2113's potential as the best-in-class oral agent for psoriasis," said Dinesh V. Patel, PhD, President and CEO of Protagonist. "We continue to believe that JNJ-2113 can potentially have a transformative impact on the treatment of psoriasis and look forward to its assessment across a spectrum of other IL-23-mediated diseases, including the Phase 2b ANTHEM ulcerative colitis study."

In FRONTIER 2, JNJ-2113 maintained high rates of skin clearance through 52 weeks in adults with moderate-to-severe plaque psoriasis. In the five JNJ-2113 treatment groups, response rates were maintained from Week 16 to Week 52 with the highest PASI 75 response observed in the 100 mg twice daily group (78.6% at 16 weeks and 76.2% at 52 weeks). Similar to the primary endpoint, responses were maintained through Week 52 for all five JNJ-2113 treatment groups for the key secondary endpoints of PASI 90 (59.5% at 16 weeks and 64.3% at 52 weeks), PASI 100 (40.5% at 16 weeks and 40.5% at 52 weeks), Investigator's Global Assessment (IGA) 0/1 (64.3% at 16 weeks and 73.8% at 52 weeks) and IGA 0 (45.2% at 16 weeks and 42.9% at 52 weeks).

A summary of PASI responder data from the FRONTIER 2 study at Week 52:

Safety in the FRONTIER 2 long-term extension study (Week 17 through Week 52) was found to be consistent with the observations made in the FRONTIER 1 study. Treatment was generally well tolerated, and the proportions of patients with adverse events were comparable between patient groups. There was no evidence of dose-dependent increase in AEs across the treatment groups.

The four Phase 3 ICONIC studies in the clinical development program are currently underway to evaluate the safety and efficacy of JNJ-2113 in adults with moderate-to-severe plaque PsO, including the ICONIC-LEAD and ICONIC-TOTAL studies. The ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 will evaluate the safety and efficacy of JNJ-2113 compared with both placebo and deucravacitinib. In addition, J&J is enrolling the Phase 2b ANTHEM-UC study to evaluate the safety and effectiveness of JNJ-2113 compared with placebo in participants with moderately-to-severely active ulcerative colitis.

About FRONTIER 2

FRONTIER 2 (NCT05364554) is a Phase 2b multicenter, double-blind, long-term extension, dose-ranging study to evaluate the efficacy and safety of JNJ-77242113 (JNJ-2113) for the treatment of moderate-to-severe plaque psoriasis. The study evaluated four once-daily and two twice-daily dosages of JNJ-2113 taken orally. The originating study (FRONTIER 1) began with its first participant screened on February 3, 2022. A total of 337 participants were screened of which 255 participants were randomized into six treatment groups (Placebo (n=43), 25 mg daily (n=43), 50 mg daily (n=43), 25 mg twice daily (n=41), 100 mg daily (n=43), 100mg twice daily (n=43)). At Week 16, a total of 227 participants from FRONTIER 1 entered FRONTIER 2, the long-term extension study, and received at least one dose of study intervention (Placebo switched to 100 mg daily (n=35), 25 mg daily (n=35), 50 mg daily (n=39), 25 mg twice daily (n=40), 100 mg daily (n=40), 100 mg twice daily (n=38)). The first participant in FRONTIER 2 study was dosed on June 10, 2023. The total duration of the trial was 52 weeks.

About JNJ-77242113 (JNJ-2113)

JNJ-2113 was jointly discovered and is being developed pursuant to the license and collaboration agreement between Protagonist and J&J, which retains 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. The license and collaboration agreement, established in 2017, enabled the companies to work together to discover and develop next-generation compounds that ultimately led to JNJ-2113.

Investigational JNJ-2113 is the first targeted oral peptide designed to block the IL-23 receptor, which underpins the inflammatory response in moderate-to-severe plaque psoriasis (PsO) and other IL-23-mediated diseases. JNJ-2113 binds to the IL-23 receptor with single-digit picomolar affinity and has demonstrated potent, selective inhibition of IL-23 signaling in human T cells. IL-23 plays a critical role in pathogenic T-cell activation in moderate-to-severe plaque PsO and underpins the inflammatory response in PsO and other dermatological, rheumatological and gastroenterological IL-23-mediated diseases.

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 and JNJ scientists jointly discovered PN-235 (now known as JNJ-2113) as part of Protagonist's Interleukin-23 receptor (IL-23R) collaboration with JNJ and followed it through IND-enabling pre-clinical and Phase 1 studies, with JNJ 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 will be co-developed and co-commercialized with Takeda pursuant to a worldwide collaboration and license agreement with Takeda entered into in January 2024. The agreement will be effective upon the termination or expiration of any applicable waiting periods under the Hart-Scott-Rodino Act.

More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company's website at 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 clinical profile 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, our ability to earn milestone payments under our collaboration agreement with JNJ, 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
+1 212 915 2577
cdavis@lifesciadvisors.com

Media Contact:

Virginia Amann, Founder/CEO
ENTENTE Network of Companies
virginiaamann@ententeinc.com

SOURCE: Protagonist Therapeutics