Protagonist Reports Final Results From Rusfertide Phase 2 REVIVE Study Showing Durable Hematocrit Control at the ASH 2024 Annual Meeting

54% of patients experience more than 2.5 years of durable hematocrit (Hct) control (<45%), decreased phlebotomy use, long-term tolerability, and improvements in patient-reported outcomes in patients with polycythemia vera

NEWARK, CA / ACCESSWIRE / December 9, 2024 / Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") announced details from a poster presentation with final data from the rusfertide Phase 2 REVIVE study. Rusfertide, a mimetic of the natural hormone hepcidin, has potential therapeutic value in the treatment of polycythemia vera (PV) and other disease indications. The data were presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, taking place December 7-10, 2024. A copy of the presentation will be available on the Events and Presentations section of the Protagonist website.

Aaron T Gerds, M.D., Associate Professor in Hematology and Medical Oncology at the Cleveland Clinic Taussig Cancer Institute, presented the final data set from the REVIVE Phase 2 study (NCT04057040). The Phase 2 trial consisted of three parts including 70 patients in the dose-finding Part 1 (28 weeks), 59 patients in the blinded, placebo-controlled, randomized withdrawal Part 2 (13 weeks), and 58 patients in the Part 3 Open Label Expansion (OLE, 52 weeks). As of October 18, 2024 (the data cut-off date for presentation at ASH), 50 (71%), 38 (54%), and 17 (24%) patients received rusfertide for ≥2, ≥2.5, or ≥3 years, respectively. Of the 58 patients who entered the REVIVE Part 3 OLE, the median duration of therapy is 131.4 weeks (2.5 years) as of the October 18, 2024 data cut-off; 46 patients have rolled over to the THRIVE study (NCT06033586) and are eligible to receive up to two additional years of rusfertide treatment.

"The final data from REVIVE show that rusfertide, when added to therapeutic phlebotomy with or without cytoreductive therapy, provided long-term durable control of hematocrit and decreased the need for phlebotomy significantly in patients with PV," said Arturo Molina, M.D., M.S., Chief Medical Officer of Protagonist. "Rusfertide was well-tolerated, with the most common adverse events being mild to moderate. Of the 58 patients in the open label extension portion of REVIVE, nearly 80% chose to enroll in the Phase 2 THRIVE OLE study, which will continue to assess the long-term safety and efficacy of rusfertide treatment for up to 2 additional years."

• Final results show that rusfertide, when added to therapeutic phlebotomy with or without cytoreductive therapy achieved long term durable control of hematocrit below the 45% threshold for over 3 years.

• Prior to enrollment, the estimated mean phlebotomy rate (EPHL) in patients who enrolled on study was >5/year:

  • In Part 1, the EPHL was <1/year in patients who received rusfertide (N=70).

  • In Part 2 (randomized withdrawal phase), the EPHL was <1/year and approximately 6.1/year in the rusfertide and placebo groups, respectively.

  • For patients who continued to Part 3 (Week 42+), the EPHL remained at <1/year.

• Increased mean corpuscular volume (MCV)and showed continued improvement and normalization of serum ferritin levels.

• Platelet levels increased following initiation of rusfertide therapy and stabilized over time; mean leukocyte counts remained stable throughout the study.

• The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)[1]^,[2] was used to assess mean change from baseline in the individual symptom score in patients with moderate (score, 4-6 of 10) or severe (score, 7-10 of 10) symptoms at baseline. In patients who had moderate or severe symptoms at baseline (≥4 of 10), there were significant improvements from baseline in fatigue, early satiety, abdominal discomfort, inactivity, problems with concentration, night sweats, and itching at the end of Part 3.

• Overall, 18 (26%) patients experienced serious adverse events (SAEs); most SAEs were unrelated and likely associated with the underlying disease.

  • One patient developed acute myeloid leukemia after treatment discontinuation.

  • After more than 150 patient-years of rusfertide exposure, malignancies were reported in 11 patients (9 patients had skin malignancies); all of these patients had risk factors that may have contributed to development of these malignancies. There was no obvious correlation between increased exposure to rusfertide and malignancies reported.

  • Seven thrombotic events (6 arterial and 1 venous) occurred in 6 patients; all had high-risk PV. No thrombotic events have been reported in patients with low-risk PV

"With these results, rusfertide continues to demonstrate a positive clinical impact in the treatment of PV patients, and we look forward to VERIFY Phase 3 topline results in the first quarter of 2025," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. "Protagonist is immensely grateful to the patients, study staff, principal investigators, and many others who made the REVIVE trial possible. With more than three years of data showing strong and lasting improvements in hematocrit as well as encouraging evidence of symptoms improvement, rusfertide continues to demonstrate its potential as a first-in-class erythrocytosis-focused treatment option for patients with PV."

About Protagonist

Protagonist Therapeutics is a late-stage development biopharmaceutical company. Two novel peptides derived from Protagonist's proprietary discovery platform are currently in advanced Phase 3 clinical development, with New Drug Application submissions to the FDA potentially in 2025. Icotrokinra (JNJ-2113, formerly PN-235), is the first targeted oral peptide designed to selectively block the IL-23 receptor, which underpins the inflammatory response in moderate-to-severe plaque PsO and other IL-23-mediated diseases. Icotrokinra binds to the IL-23 receptor with single-digit picomolar affinity and demonstrated potent, selective inhibition of IL-23 signaling in human T cells. Icotrokinra is licensed to Johnson & Johnson and is currently in Phase 3 development for psoriasis and is nearing completion of Phase 2b development for ulcerative colitis. Following icotrokinra's joint discovery by Protagonist and Johnson & Johnson scientists pursuant to the companies' IL-23R collaboration, Protagonist was primarily responsible for development of icotrokinra through Phase 1, with Johnson & Johnson assuming responsibility for development in Phase 2 and beyond. Rusfertide, a mimetic of the natural hormone hepcidin, is currently in Phase 3 development for the rare blood disorder polycythemia vera. Rusfertide is being co-developed and will be co-commercialized with Takeda Pharmaceuticals pursuant to a worldwide collaboration and license agreement entered into in 2024 under which the Company remains primarily responsible for development through NDA filing. The Company also has a number of pre-clinical stage oral drug discovery programs addressing clinically and commercially validated targets, including IL-17, hepcidin mimetic, and anti-obesity programs.

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, the timing of rusfertide clinical trial data, and timing of developments and announcements in our discovery programs. 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 agreements with Janssen and Takeda, 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.

[1] Scherber R, et al. Blood. 2011;118(2):401-8.

[2] Emanuel RM, et al. J Clin Oncol. 2012;30(33):4098-103.