Rusfertide met the study's primary endpoint, with a statistically significant higher number of responders on rusfertide versus placebo (p=0.0003)

Rusfertide continues to be generally well tolerated with no new safety signals

NEWARK, CA / ACCESSWIRE / March 15, 2023 / Protagonist Therapeutics, Inc. (NASDAQ:PTGX) ("Protagonist" or "the Company"), today announced positive topline results from the blinded, placebo-controlled, randomized withdrawal portion of REVIVE, a study evaluating rusfertide, a subcutaneous injectable hepcidin mimetic, in patients with polycythemia vera (PV). Subjects receiving rusfertide achieved highly statistically significant improvements versus placebo in the primary endpoint.

The double-blind, placebo-controlled, 12-week randomized withdrawal phase was included as Part 2 of the REVIVE study to evaluate rusfertide in PV patients with frequent phlebotomy requirements. In the trial, study subjects were initially enrolled in the 28-week open label dose-titration and efficacy evaluation Part 1 of the study, followed by 1:1 randomization of 53 subjects to placebo versus rusfertide therapy for a subsequent duration of 12 weeks ("randomized withdrawal portion" or "Part 2").

More subjects receiving rusfertide during the blinded randomized withdrawal portion of the REVIVE study were responders compared with placebo (69.2% versus 18.5%, p=0.0003). A study subject was defined as a responder if the subject completed 12 weeks of double-blind treatment while maintaining hematocrit control without phlebotomy eligibility and without phlebotomy. During the 12 weeks of the blinded randomized withdrawal, only 2 of 26 subjects on rusfertide were phlebotomized, keeping 92.3% patients phlebotomy free in the rusfertide arm (p=0.0003).

In patients with moderate or severe Myeloproliferative Neoplasm-Symptom Assessment Form (MPN-SAF) symptom scores at baseline, the change from baseline was statistically significant in fatigue, problems with concentration, inactivity and itching during the 28-week open label Part 1 of the study. Meaningful comparison of symptom assessments in Part 2 are not possible since a majority of subjects randomized to placebo discontinued prior to the 12-week assessment of MPN-SAF symptoms.

Rusfertide was well tolerated, with localized injection site reactions comprising the majority of reported adverse events. No new safety signals were observed in these data following presentation of safety data from the REVIVE study at the American Society of Hematology (ASH) December 2022 Annual Meeting.

Additional details on these data can be found in slides 25 through 31 of the Protagonist Corporate Presentation, available on the Company's website at protagonist-inc.com.

"Participants in our studies who required frequent phlebotomy, with or without cytoreductives, have now been treated with rusfertide for more than two years, remaining largely phlebotomy free," said Arturo Molina, M.D., M.S., Chief Medical Officer of Protagonist. "Data from the REVIVE study suggest that rusfertide treatment results in a highly statistically significant reduction in the need for therapeutic phlebotomy in phlebotomy-dependent patients, leading to rapid, sustained, and durable control of hematocrit levels below 45%. Part 2 of REVIVE, the randomized withdrawal study, yielded no new safety findings while confirming previously reported efficacy and safety findings observed in the open label portion of REVIVE (Part 1)."

"These randomized withdrawal data from the REVIVE study indicate a dramatic difference in the experience of the treatment group versus the placebo group," noted Dr. Ronald Hoffman, M.D., the Albert A. and Vera G. List Professor of Medicine (Hematology and Oncology), Director of the Myeloproliferative Research Program at the Icahn School of Medicine at Mount Sinai, and principal investigator of the study. "With robust and strongly positive results observed across a diverse set of patients, we now have further confirmation of rusfertide's potential to serve as an important future treatment option for patients with polycythemia vera."

"All study subjects who participated in the REVIVE clinical trial had been previously unsuccessful in controlling their hematocrit using standard-of-care therapies alone," said Andrew Kuykendall, M.D., Department of Malignant Hematology, Moffit Cancer Center. "These new data from REVIVE provide important insights into the role that rusfertide (PTG-300) can potentially have within a future PV treatment paradigm, supporting patients and their physicians in achieving the treatment goal of hematocrit below 45%, in step with current NCCN Clinical Practice Guidelines."

"The new randomized withdrawal data confirm our previous efficacy and safety findings of rusfertide in PV and support our strong conviction that rusfertide can be a potentially transformational therapeutic option for polycythemia vera," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer of Protagonist. "With the completion of the REVIVE study, the Company's topmost priority continues to be execution of the 250-patient global, pivotal, Phase 3 VERIFY study in PV. The Protagonist team continues to work with full dedication alongside investigators, site staff and other partners with the shared aim of bringing this important potential therapy to PV patients."

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 the potential benefits to patients of rusfertide. 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, 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 - j.taylor@ptgx-inc.com

SOURCE: Protagonist Therapeutics, Inc.