Long term follow-up from REVIVE Phase 2 study shows durable hematocrit control, decreased phlebotomy use, long-term tolerability, and no new safety signals in patients with polycythemia vera

Analysis of PACIFIC Phase 2 study shows that rusfertide improves markers of iron deficiency in patients with polycythemia vera

Prevalence of thromboembolic events and secondary cancers in polycythemia vera presented based on a retrospective analysis of real-world claims data

NEWARK, CA / ACCESSWIRE / December 12, 2023 / Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") announced details from five abstracts at the American Society of Hematology 2023 Annual Meeting, including an oral presentation with two-year follow up data from the Phase 2 REVIVE study with rusfertide, a mimetic of the natural hormone hepcidin with potential therapeutic value in the treatment of polycythemia vera (PV) and other disease indications. Copies of the presentations will be available on the Events and Presentations section of the Protagonist website.

Ellen K. Ritchie, M.D., Associate Professor of Clinical Medicine at Weill Cornell Medical College presented long-term follow up data from patients in REVIVE who continued into the open label extension (OLE). The Phase 2 trial consisted of 3 parts including 70 patients in the dose-finding Part 1, 59 patients in the placebo-controlled, randomized withdrawal Part 2, and 58 patients in the OLE. At the end of Part 2, 69% (18/26) of rusfertide patients achieved hematocrit control and remained phlebotomy free at 12 weeks, compared to only 19% (5/27) on placebo (p=0.0003). Among the 58 patients that continued into the OLE, as of October 17, 2023 (data cut-off for the ASH presentation), 57 had been treated for over one year and 37 had been treated for over two years. The median follow-up was 2.1 years and data were provided out to 2.5 years in 21 patients.

"These long-term REVIVE data underscore the impact that rusfertide has on PV patients," noted Dr. Ellen K. Ritchie. "With robust and durable improvements in hematocrit as well as improvement of symptoms as measured by validated patient reported outcomes assessments, we continue to be confident of the value rusfertide offers and its potential as an important future treatment option for patients with polycythemia vera."

Results showed that rusfertide when added to therapeutic phlebotomy with or without cytoreductive therapy through 2 years resulted in:

• long-term durable control of hematocrit well below the 45% threshold, decreased red blood cell counts and decreased phlebotomy use;

• improved and normalized serum ferritin levels; and

• no new safety signals, with the majority of adverse events being grade 1-2 injection site reactions that decreased in frequency over time, or adverse events consistent with comorbidities anticipated in the PV population

Cancers are common in PV patients and in REVIVE, 19 of 70 patients (27.1%) had a history of cancer prior to enrolling in the study. Among these patients, 10 (14.3%) had a history of skin cancer. As of October 17, 2023, there have been 8 patients diagnosed with cancer while on study and 7 (7/70; 10.0%) with skin cancer.

"We are very pleased that the 2-year OLE data from the ongoing REVIVE study continue to reflect positively on both safety and efficacy of rusfertide. The new retrospective analysis presented at ASH on the incidence of cancers in PV patients not treated with rusfertide demonstrates the heightened underlying cancer risk in this population, particularly among those treated with hydroxyurea," said Arturo Molina, M.D., M.S., Chief Medical Officer of Protagonist. "Additionally, the majority of patients with prior thromboembolic events (TE), who are at highest risk of developing a TE, did not experience recurrent TEs while on rusfertide."

A separate poster presented at ASH by Dr. Naveen Pemmaraju, of MD Anderson Cancer Center titled "Prevalence of Second Cancers in Patients with Polycythemia Vera (PV): A Retrospective Analysis of US Real-World Claims Data," utilized data for 2007-2019 from a large US electronic health records database to examine the overall frequency of secondary cancers in patients with a primary PV diagnosis and compared those who were treated with hydroxyurea (HU) versus phlebotomy (PHL). None of these patients had received rusfertide. Among the 20,089 PV patients that qualified for this retrospective study:

• 35.7% (7,181) of patients reported at least one secondary cancer
• 9.1% (1,830) of patients reported any form of skin cancer
• 8.3% (1,659) of patients reported non-melanoma skin cancer

The mechanisms contributing to the increased risk of cancers in PV patients are not well understood. However, the subset of PV patients treated with HU in this study of real-world claims data had nearly twice the rate of cancers compared to phlebotomy-only treated patients.

In an oral presentation, Dr. Andrew T. Kuykendall, of Moffitt Cancer Center in Tampa, FL discussed a real-world retrospective analysis indicating that PV patients (not treated with rusfertide) experience high rates of arterial and venous TEs (25%). High-risk patients (classified by age or event-based risk) showed a higher risk of death than lower risk PV patients (37% vs 8.5%, respectively). The study included over 20,000 PV patients in the US via the Optum MarketClarity Database. TE incidence was highest among event-based high-risk patients (50.2%; 1634/3256), followed by age-based high-risk (25.0%; 2480/9924) and low-risk patients (13.3%; 921/6909).

"The 2-year follow-up data from REVIVE are very compelling and show the potential for a durable effect and favorable risk-benefit profile for rusfertide in PV patients," said Dinesh V. Patel, Ph.D., President and CEO of Protagonist. "Our focus continues to be execution of the 250-patient Phase 3 VERIFY study. We feel confident that results from REVIVE and a successful outcome from VERIFY would position rusfertide as an attractive erythrocytosis-specific option for PV patients who experience a need for ongoing phlebotomy despite the use of standard of care therapies."

About Protagonist

Protagonist Therapeutics, Inc. 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 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 development program. 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 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 benefits 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, 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.