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Protagonist Therapeutics to Present Updated Phase 2 Rusfertide Clinical Results in Polycythemia Vera (PV) at ASCO 2022

PTGX | May 26, 2022

Enrollment completed and dosing resumed in the ongoing Phase 2 REVIVE study

Resumption of rusfertide administration after suspension restored therapeutic benefits including hematocrit control, reduced red blood cell count, and decreased phlebotomy rate

NEWARK, Calif., May 26, 2022 /PRNewswire/ -- Protagonist Therapeutics (Nasdaq: PTGX) today announced new data from its ongoing Phase 2 REVIVE study evaluating rusfertide in patients with polycythemia vera (PV). These results will be shared as an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, being held in Chicago from June 3-7, 2022.

"We are pleased to observe that administration of rusfertide continues to provide PV patients with an effective therapy that leads to rapid and sustained hematocrit control, and potentially offers patients a better quality of life by keeping them essentially phlebotomy-free for up to 18 months," said Ronald Hoffman, M.D., Director of the Myeloproliferative Disorders Research Program at the Icahn School of Medicine at Mount Sinai and principal investigator of the REVIVE study. "Importantly, the new results show that rusfertide administration suspension, due to the brief clinical hold, directly led to increases in hematocrit levels, red blood cell counts, and phlebotomy rates. In contrast, resumption of rusfertide quickly restored the therapeutic benefits for patients, confirming the direct and rapid effect of rusfertide and its potential utility in treating this serious disease."

"These highly promising new results continue to demonstrate the rapid therapeutic effect of rusfertide and its utility as an effective potential treatment across all categories of PV patients, independent of patient risk category, or concurrent therapy with other cytoreductive treatments including hydroxyurea, interferons or JAK inhibitors," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer of Protagonist. "Taken together, these data reaffirm our belief in the potential of rusfertide to provide a highly effective treatment option for patients with PV, providing an opportunity to fundamentally transform the management of this disease. Rusfertide continues to be the primary focus of our corporate resources and efforts, and we continue to explore the full therapeutic potential of rusfertide with a sharp focus on the execution of the recently initiated Phase 3 VERIFY study."

Summary of Key Results

Updated Results from Phase 2 Studies Evaluating Rusfertide in Patients with PV

REVIVE Study

The ongoing Phase 2 REVIVE study was designed to evaluate rusfertide in patients with phlebotomy-dependent PV for up to 18 months. Results from the 70 phlebotomy-dependent PV patients continued to demonstrate that rusfertide treatment essentially eliminated the need for therapeutic phlebotomy (TP), and led to rapid, sustained, and durable control of hematocrit (HCT) levels below 45% without a clinically meaningful increase in white blood cell numbers of PV-related thromboses. Rusfertide treatment also led to normalization of iron stores and improved symptoms including concentration.

Furthermore, the new data showed that treatment suspension in PV patients led to increases in hematocrit levels, RBC count, and phlebotomy rates. In contrast, resumption of rusfertide treatment in those patients led to significant improvement in those parameters, providing further evidence of the rapid and beneficial therapeutic effect of rusfertide in PV. Upon the lifting of the clinical hold placed on rusfertide in PV, about 85% of patients resumed treatment with rusfertide.

PACIFIC Study

The ongoing Phase 2 PACIFIC study enrolled 20 patients with confirmed high HCT levels above 48% to evaluate rusfertide as an induction therapy. Results demonstrated that all erythrocytotic PV patients on rusfertide induction therapy with twice weekly dosing achieved rapid, sustained and durable HCT control below 45%, and without the need for TP.

Details for the ASCO 2022 oral presentation are as follows:

Title: Rusfertide (PTG-300) treatment in phlebotomy-dependent polycythemia vera patients.
Authors:Ronald Hoffman, M.D., The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Protagonist Therapeutics
Abstract Number: #7003
Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Presentation Date and Time: June 7, 2022 at 10:45 a.m. CT

About Rusfertide

Rusfertide (PTG-300) is an investigational, injectable hepcidin mimetic that is currently being developed for various disorders associated with iron overload and/or excessive erythrocytosis (red blood cell production). Rusfertide regulates iron homeostasis and controls the absorption, storage, and distribution of iron in the body. Discovered through Protagonist's peptide technology platform, rusfertide is currently being investigated in the REVIVE Phase 2 proof-of-concept clinical trial for polycythemia vera (PV), a rare chronic blood disorder that affects about 160,000 patients in the U.S., the PACIFIC Phase 2 study in PV subjects with high hematocrit levels, and a recently completed Phase 2a study for hereditary hemochromatosis. The VERIFY Phase 3 study is currently underway.

About Protagonist

Protagonist Therapeutics is a biopharmaceutical company with multiple peptide-based new chemical entities in different stages of clinical development, all derived from the Company's proprietary technology platform.

Protagonist's pipeline includes rusfertide, an investigational, injectable hepcidin mimetic currently in the REVIVE Phase 2 proof-of-concept clinical trial for polycythemia vera (PV), the PACIFIC Phase 2 study in PV subjects with high hematocrit levels, and a recently completed Phase 2a study for hereditary hemochromatosis. The Company has opened sites and initiated patient screening for VERIFY, a single, global Phase 3 randomized, placebo-controlled trial evaluating the efficacy and safety of a once weekly, subcutaneously self-administered dose of rusfertide for patients living with PV.

The IDEAL Phase 2 study of PN-943 in moderate-to-severe ulcerative colitis concluded in April 2022. Although this Phase 2 study missed its pre-specified primary endpoint, the results support advancement of the 150-milligram dose of PN-943 into a Phase 3 study. Efforts to secure a partner to support the financing and execution of the registrational clinical development program for PN-943 are underway.

Protagonist has granted Janssen an exclusive worldwide license to research, develop and commercialize oral IL-23 receptor antagonists based on the Company's intellectual property. Current development efforts are centered on PN-235, discovered by Protagonist and further developed in collaboration with Janssen. FRONTIER 1, a Phase 2b multicenter, randomized, placebo controlled, dose-ranging study to evaluate the safety and efficacy of PN-235 for the treatment of moderate-to-severe plaque psoriasis, commenced in early 2022.

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 our intentions or current expectations concerning, among other things, the clinical development of rusfertide and the potential of rusfertide in polycythemia vera. 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, the impact of the current COVID-19 pandemic on our discovery and development efforts, the impact of the ongoing military conflict in Ukraine and Russia on any future studies, 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.