Protagonist Therapeutics

MIMRYLO™ (rusfertide) Approved by FDA for the Treatment of Erythrocytosis in Adults with Polycythemia Vera; Approval Triggered $275 Million in Payments to Protagonist

Comprehensive Phase 2b Program with PN-881, an Oral IL-17 Antagonist for Psoriasis, Planned to Initiate in Early Q1 2027

$300 Million Share Repurchase Program Announced in September 2026

Cash, Cash Equivalents and Marketable Securities of $834.6 Million as of September 30, 2026

MIMRYLO^™ is the First and Only Hepcidin Mimetic Peptide Therapy Approved for the Treatment of Erythrocytosis in Adults with Polycythemia Vera, Offering a Novel Mechanism to Maintain Hematocrit Control, Meaningfully Reduce Phlebotomy Burden, and Improve Fatigue

Approval Supported by Phase 3 VERIFY Results Showing 76.9% of Patients Achieved Response During Weeks 20-32

FDA Approval Triggers $275M in Milestones, 14%-29% Royalties, with Up to an Additional $875M in Potential Future Milestones

Investor call to be held Monday, August 31st at 8:30 am ET

ICOTYDE^™ First Full Quarter of Commercial Sales with Strong Early Adoption

Rusfertide NDA under Priority Review for Polycythemia Vera; PDUFA Date in August 2026

Comprehensive Phase 2b Program with PN-881, an Oral IL-17 Antagonist for Psoriasis, Planned to Initiate Early Q1 2027

Phase 1 Study Initiated with PN-477sc, a Triple GLP1/GIP/GCG Agonist Peptide for Obesity

Cash, Cash Equivalents and Marketable Securities of $849.5 Million as of June 30, 2026

ICOTYDE™ (icotrokinra) approved by FDA in March for moderate-to-severe plaque psoriasis, triggering a $50 million milestone payment; Protagonist receives tiered royalties of 6% to 10% and is eligible for up to $580 million in future milestone payments

Rusfertide NDA accepted and granted Priority Review by FDA, with a Prescription Drug User Fee Act target action date in the third quarter of 2026

Protagonist exercised its rusfertide opt-out right under the Takeda collaboration on April 28, triggering a $200 million opt-out fee payable to the Company; eligible for additional $200 million opt-out and $75 million milestone payments upon NDA approval, sales milestones of up to $775 million and worldwide royalties ranging from 14% to 29%

PN-881 (oral IL-17 antagonist peptide) Phase 1 study completion by mid-2026 and Phase 2 initiation anticipated by year-end; PN-477sc and PN-477o (sc and oral triple GLP/GIP/GICG agonist) Phase 1 initiation expected in mid-2026 and Q1 2027, respectively

Cash, cash equivalents and marketable securities of $620 million as of March 31, 2026, anticipated to provide cash runway through at least 2028

Opt-out election makes Protagonist eligible for $200 million upon exercise and an additional $200 million upon FDA approval of rusfertide for polycythemia vera

Approval would also trigger a $75 million milestone payment, bringing total potential cash tied to the opt-out election and approval to $475 million

Protagonist becomes eligible for up to $975 million in milestone payments and tiered royalties ranging from 14% to 29% on worldwide net sales

One-year Phase 3 data for ICOTYDE to be presented at AAD 2026 demonstrate lasting skin clearance and a favorable safety profile in a once daily pill for moderate-to-severe plaque psoriasis

Results further support the differentiated profile of ICOTYDE, the first and only IL-23 receptor targeted oral peptide

$50 million milestone payment triggered by FDA approval; Protagonist is eligible to receive 6 - 10% royalties on sales and up to $580 million in future milestone payments

Webcast and conference call to be held at 8:30 am ET on March 18

(This release updates the release that posted earlier on February 25, 2026 to update the sub headlines.)

NDA for rusfertide submitted to the US Food and Drug Administration (FDA), with potential approval and launch this year

Company expects to opt-out of the 50:50 profit and loss sharing arrangement for rusfertide with Takeda during a 90-day window expected to open in Q2

U.S. regulatory decision for ICOTYDE^TM (icotrokinra) anticipated in 2026 with potential launch this year

PN-881 Phase 1 completion expected by mid-2026

Pre-clinical pipeline expanded with novel wholly-owned candidates PN-477, an oral and s.c. triple GLP-GIP-GCG agonist and PN-458, an oral and s.c. dual GLP-GIP agonist, and PN-8047, an oral hepcidin functional mimetic

Cash, cash equivalents and marketable securities of $646 million as of December 31, 2025, anticipated to provide cash runway through at least end of 2028

NDA for rusfertide submitted to the US Food and Drug Administration (FDA), with potential approval and launch this year

Company expects to opt-out of the 50:50 profit and loss sharing arrangement for rusfertide with Takeda during a 90-day window expected to open in Q2

U.S. regulatory decision for ICOTYDE^TM (icotrokinra) anticipated in 2026 with 
potential launch this year

PN-881 Phase 1 completion expected by mid-2026

Following the NDA submission for icotrokinra treatment of adults and adolescents with moderate to severe plaque psoriasis to the U.S. FDA in July, the European Medicines Agency (EMA) application was submitted in September

Rusfertide granted breakthrough designation for patients in Polycythemia Vera (PV) and the subject of four presentations including 52-week results of the VERIFY Phase 3 Study at ASH, the 67^th Annual American Society of Hematology (ASH) meeting in December

First patient dosed in the Phase 1 trial of PN-881, a first-in-class oral IL-17 peptide antagonist

IND-enabling studies progressing as planned with triple-GLP/GIP/GCG agonists PN-477sc and PN-477o

Oral hepcidin development candidate expected to be nominated by year end

Cash, cash equivalents and marketable securities of $678.8 million as of September 30, 2025, anticipated to provide cash runway through at least end of 2028

Icotrokinra demonstrated clinically meaningful outcomes at Week 28 in the Phase 2b ANTHEM-UC study in ulcerative colitis, with 31.7% of patients achieving clinical remission and 38.1% showing endoscopic improvement versus placebo

Updated ANTHEM-UC data support Phase 3 clinical development of icotrokinra in both moderately to severely active ulcerative colitis and Crohn's disease

In areas of high impact, 72% of patients with scalp psoriasis and 85% with genital psoriasis treated with icotrokinra achieved site-specific clear or almost clear skin at Week 52 in Phase 3 ICONIC-TOTAL study

Further, 67% of patients treated with icotrokinra in the ICONIC-TOTAL study achieved overall rates of clear or almost clear skin by Week 24, which was maintained through Week 52

Icotrokinra met the primary endpoint of clinical response at all three doses, with 36.5% of patients treated achieving endoscopic improvement and 30.2% achieving clinical remission at the highest dose at Week 12 in the Phase 2b ANTHEM-UC study

These data support the promise of a first-in-class targeted oral peptide that selectively blocks the IL-23 receptor as a potential new option for people with moderately to severely active ulcerative colitis

Registrational Phase 3 study in ulcerative colitis and Phase 2b/3 study in Crohn's disease anticipated to begin patient enrollment in Q4 2025

Icotrokinra demonstrated superior skin clearance at Weeks 16 and 24 compared to deucravacitinib and similar adverse event rates to placebo in Phase 3 ICONIC-ADVANCE studies

Icotrokinra also showed sustained skin clearance and favorable safety profile in both adults and adolescents at Week 52 in Phase 3 ICONIC-LEAD study

Preclinical proof-of-concept data on PN-881, a first-in-class oral peptide targeting the IL-17 pathway, and part of Protagonist's fully owned development pipeline, including the highly potent and selective binding of IL-17A and IL-17F

Icotrokinra is a first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor ¹

Filing based on four Phase 3 studies that met all primary and co-primary endpoints. This unprecedented data package includes head-to-head superiority comparisons versus deucravacitinib, adolescent data, and evaluation of difficult to treat skin sites^2,3,4,5,6

Submission underscores that icotrokinra has the potential to offer moderate-to-severe plaque psoriasis patients the combination of complete skin clearance and a favourable safety profile, relative to comparators, with the simplicity of a once-daily tablet. ^2,3,4,5,6

Breakthrough Therapy designation complements Rusfertide's Orphan Drug and Fast Track designations, which together confer multiple benefits to the development program

U.S. New Drug Application filing for Rusfertide in polycythemia vera on track for Q4

NDA for icotrokinra for the treatment of adults and adolescents 12 years of age and older with moderate to severe plaque psoriasis (PsO) submitted to U.S. FDA in July

ANTHEM Phase 2b trial data of icotrokinra in ulcerative colitis scheduled for an oral presentation at the 33^rd United European Gastroenterology Week (UEGW) on October 7^th

Phase 3 VERIFY trial data set of rusfertide in polycythemia vera (PV) presented during plenary session at ASCO; U.S. NDA filing on track for Q4

Cash, cash equivalents and marketable securities of $673.0 million as of June 30, 2025, anticipated to provide cash runway through at least end of 2028

Icotrokinra is a first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor

Filing based on unprecedented data package that met all primary endpoints across four Phase 3 studies, including head-to-head superiority comparisons versus deucravacitinib and evaluation of difficult to treat skin sites

Submission underscores potential to offer moderate-to-severe plaque psoriasis patients the standout combination of complete skin clearance, favorable safety profile, and simplicity of a once-daily pill

A novel oral peptide PN-477o with once-daily dosing, high potency and activation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon (GCG) receptors

Company will also develop a subcutaneous version, PN-477sc, as a once-weekly injection

IND-enabling studies underway, with Phase I study initiation expected in 2Q26

Webcast and conference call to be held today at 4:30 pm ET

Webcast and conference call to be held on Monday, June 30th at 4:30 pm ET, dial in information below

Data from icotrokinra ICONIC-TOTAL show 66% of patients with scalp psoriasis and 77% with genital psoriasis achieved site-specific clear or almost clear skin at Week 16

Icotrokinra continues to demonstrate a standout combination of significant skin clearance (IGA 0/1) and a favorable safety profile in a once daily pill

PN-881, a first-in-class oral peptide targeting the IL-17 pathway, potently and selectively binds IL-17A and -17F, blocking the three dimeric forms of the cytokine

Positive top line results from rusfertide Phase 3 VERIFY trial in polycythemia vera (PV) announced; full data selected for oral presentation during plenary session at ASCO on June 1^st

Conference call to be held June 2^nd at 8AM EDT to discuss rusfertide data presented at ASCO

Full dataset from Phase 3 ICONIC-LEAD trial with icotrokinra in patients with moderate-to-severe plaque psoriasis (PsO) presented at the 2025 AAD Meeting in March; data from adolescent subset presented at World Congress of Pediatric Dermatology in April

Positive top line results from icotrokinra Phase 2b ANTHEM trial in moderately to severely active ulcerative colitis (UC) announced in March, data to be presented at medical conference later in 2025

Cash, cash equivalents and marketable securities of $697.9 million as of March 31, 2025, anticipated to provide cash runway through at least end of 2028

84% of adolescents with moderate-to-severe plaque psoriasis treated with investigational icotrokinra achieved clear or almost clear skin (IGA 0/1) at Week 16

ICONIC-LEAD is the first ever Phase 3 registrational study in moderate-to-severe plaque psoriasis to assess safety and efficacy of a systemic therapy in adolescents and adults simultaneously

Past Winners include Waymo, Nvidia, Duolingo, and Novo Nordisk, among others

Clinical response rate of 63.5% and clinical remission rate of 30.2% achieved at Week 12 with the highest dose, which continued to improve through Week 28

All three doses met the primary endpoint of clinical response at Week 12, with a favorable safety profile

These results in ulcerative colitis build on strong data recently reported for the plaque psoriasis Phase 3 program

Nearly half of patients with moderate-to-severe plaque psoriasis (PsO) treated with icotrokinra achieved completely clear skin (IGA 0) at Week 24 in Phase 3 ICONIC-LEAD study

Topline results from Phase 3 ICONIC-ADVANCE 1&2studies show icotrokinra achieved co-primary endpoints and showed superiority to deucravacitinib in moderate-to-severe PsO

Results pave the way to initiate the first-ever head-to-head study (ICONIC-ASCEND) seeking to demonstrate the superiority of a pill versus injectable biologic in moderate-to-severe PsO

$165.0 million icotrokinra (formerly JNJ-2113) milestone earned in Q4 2024, received in January 2025

PN-881, a potential best-in-class oral IL-17 receptor antagonist peptide nominated as a development candidate in Q4 2024

Topline results for rusfertide Phase 3 VERIFY clinical trial in polycythemia vera expected in March 2025

Topline results for icotrokinra Phase 2b ANTHEM clinical trial in moderate to severe ulcerative colitis expected in March 2025

Cash, cash equivalents, and marketable securities of $559.2 million as of December 31, 2024, combined with $165.0 million milestone payment, anticipated to provide cash runway through at least end of 2028

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

Oral peptide with biologics-like high potency and spectrum of activity against three therapeutically relevant dimeric forms of IL-17 (AA, AF and FF)

IND enabling studies underway, with Phase I initiation expected in Q425

Webcast and conference call to be held today at 4:30 pm ET