On November 8, 2022 Protagonist Therapeutics (Nasdaq: PTGX) ("Protagonist" or "the Company") reported financial results for the third quarter ended September 30, 2022 and provided a corporate update (Press release, Protagonist, NOV 8, 2022, View Source [SID1234623411]).

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"Continued execution of the Phase 3 VERIFY global clinical development program of rusfertide in polycythemia vera remains our top corporate priority," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer of Protagonist. "Rusfertide has the potential to transform the current treatment paradigm for PV, dramatically improving patients’ lives. The enthusiasm we have observed around rusfertide, among patients and physicians alike, reinforces our commitment to advancing this important drug candidate as rapidly as possible."

Dr. Patel continued, "We are pleased to have recently announced a new Chief Medical Officer, Dr. Arturo Molina, a renowned hematologist-oncologist and a successful drug developer. Dr. Molina will focus on providing medical and operational leadership to our rusfertide clinical development program.

"Our Janssen-partnered asset, PN-235 (JNJ-77242113), an oral peptide interleukin 23 receptor (IL-23R) antagonist, is currently in multiple Phase 2 clinical studies to assess safety and efficacy in moderate-to-severe plaque psoriasis. We look forward to decision-driving results from these studies in the first half of next year. With important pending readouts for both rusfertide and PN-235, we expect the first half of 2023 to be a period of potential transformational value creation for Protagonist."

Third Quarter 2022 and Recent Developments

Rusfertide: Subcutaneous Injectable Hepcidin Mimetic for Polycythemia Vera (PV) and Other Potential Indications

While significant efforts have been undertaken toward the goal of full enrollment of the Phase 3 VERIFY study, and a high degree of interest has been observed from physician and patient communities, operational challenges including site staff shortages have continued to delay initial recruitment activities. The Company expects enrollment completion in the second half of 2023.
Protagonist will have three poster presentations at the 2022 ASH (Free ASH Whitepaper) Annual Meeting & Exposition, taking place December 10-13 in New Orleans, Louisiana. Details are as follows:
Poster Presentation 1:
Title: VERIFY: A Phase 3 Study of the Hepcidin Mimetic Rusfertide (PTG-300) in Patients with Polycythemia Vera
Session Name: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Session Date: Saturday, December 10, 2022
Presentation Time: 5:30 PM – 7:30 PM CT.
Poster Presentation 2:
Title: Subgroup Analysis of Adverse Events Following Rusfertide Dosing in REVIVE: A Phase 2 Study of Patients with Polycythemia Vera
Session Name: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster II
Session Date: Sunday, December 11, 2022
Presentation Time: 6:00 PM – 8:00 PM CT.
Poster Presentation 3:
Title: Rusfertide Analog-PN23114 as a Hepcidin Mimetic Provides Efficacy Benefits in Conjunction with Phlebotomy in Mouse Model for Hereditary Hemochromatosis
Session Name: 102. Iron Homeostasis and Biology: Poster II
Session Date: Sunday, December 11, 2022
Presentation Time: 6:00 PM – 8:00 PM CT.
In keeping with the Company’s organizational prioritization of rusfertide in PV, plans to initiate studies of rusfertide in additional disease indications have been paused. This decision was influenced in part by enactment of the Inflation Reduction Act in the U.S. and includes previously planned studies of rusfertide in the subset of hereditary hemochromatosis (HH) patients with chronic arthropathy.
PN-235: Oral IL-23 Receptor Antagonist

Four clinical studies of PN-235 (JNJ-77242113), a drug candidate discovered by Protagonist and further developed in collaboration with Janssen, are underway and led by Janssen:
FRONTIER 1, a Phase 2b multicenter, randomized, placebo controlled, 240-patient dose-ranging study commenced in early 2022 to evaluate the safety and efficacy of PN-235 for the treatment of moderate-to-severe plaque psoriasis;
FRONTIER 2, a long-term extension study in moderate-to-severe plaque psoriasis;
SUMMIT, a study of an oral tablet formulation of PN-235 for the treatment of moderate-to-severe plaque psoriasis; and
A separate Phase 1 study of PN-235 in healthy Japanese and Chinese participants. More information on these studies can be found at View Source
Protagonist expects the results of these studies to inform the next steps for PN-235 development. To date, $112.5 million in development milestones have been received and the Company remains eligible for up to approximately $855.0 million in future development and sales milestones. In the near term, the Company is eligible for a $10 million milestone payment in connection with the start of a second indication-based Phase 2 study, and a $50 million milestone upon dosing of a third patient in a Phase 3 study of PN-235.
PN-943: Oral, Gut-Restricted, alpha-4-beta-7 Integrin Antagonist for Ulcerative Colitis (UC)

With the exception of completing the 40-week extended treatment period for eligible patients in the Phase 2 IDEAL study, expected to be completed in Q1 2023, the Company intends to dedicate no further internal resources to clinical development or CMC activities for PN-943. The Company will continue to explore out-licensing opportunities globally.
Management and Operational Updates

Arturo Molina, M.D., M.S. has joined Protagonist as its Chief Medical Officer (CMO). Dr. Molina’s responsibilities will include strategic and execution leadership across the Company’s clinical development programs, with a primary focus on the Phase 3 VERIFY study of rusfertide in PV.
Dr. Molina comes most recently from Sutro Biopharma, where he was Chief Medical Officer for more than six years. Previously, from 2013 to 2016, Dr. Molina was Vice President, Oncology Scientific Innovation, at Johnson & Johnson.
De-prioritization of the PN-943 program and streamlining of certain discovery programs is part of Company’s ongoing commitment to optimize and focus resources toward the rusfertide program in PV.
Third Quarter 2022 Financial Results

Cash, Cash Equivalents and Marketable Securities: Cash, cash equivalents and marketable securities as of September 30, 2022 were $267.4 million. The Company expects current cash, cash equivalents and marketable securities to be sufficient to fund its planned operating and capital expenditures through the end of 2024.
License and Collaboration Revenue: License and collaboration revenue was zero and $26.6 million for the three and nine months ended September 30, 2022, respectively, as compared to $10.3 million and $18.7 million, respectively, for the same periods in 2021. The decrease in revenue from prior year quarter was primarily due to a decrease in the level of services the Company provided under the Janssen license and collaboration agreement. The Company completed its performance obligation pursuant to the collaboration as of June 30, 2022. The revenue increase from prior year-to-date included the $25.0 million milestone that the Company became eligible to receive in March 2022 upon the dosing of the third patient in the Janssen Phase 2b FRONTIER 1 study of PN-235.
Research and Development ("R&D") Expenses: R&D expenses were $25.4 million and $96.3 million for the three and nine months ended September 30, 2022 as compared to $37.0 million and $87.6 million for the same periods in 2021. The decrease in R&D expense from prior year quarter was primarily due to lower PN-943 expenses related to the suspension of further program expenditures and the impact of $4.0 million recorded during the third quarter of 2021 related to the resolution of the Company’s collaboration agreement dispute with Zealand Pharma. The increase in R&D expense from prior year to date was primarily due to costs associated with rusfertide and PN-943, including current and planned Phase 3 clinical trials, partially offset by a decrease in costs related to the completion of PN-235 and PN-232 Phase 1 trials and the impact of $4.0 million recorded during the third quarter of 2021 related to the resolution of the Company’s collaboration agreement dispute with Zealand Pharma.
General and Administrative ("G&A") Expenses: G&A expenses were $6.9 million and $25.1 million for the three and nine months ended September 30, 2022 as compared to $7.3 million and $19.9 million for the same periods in 2021. The decrease from prior year quarter was primarily due to decreases in consulting, legal and other expenses. The increase from prior year to date was primarily due to increases in personnel related and other expenses to support Company growth.
Net Loss: Net loss was $31.2 million, or $0.64 per share, for the three months ended September 30, 2022 as compared to a net loss of $33.8 million, or $0.70 per share, for the three months ended September 30, 2021. Net loss was $93.2 million, or $1.90 per share, for the nine months ended September 30, 2022 as compared to a net loss of $88.6 million, or $1.94 per share for the nine months ended September 30, 2021.