Protagonist Therapeutics, Inc. · NASDAQ:PTGX
Protagonist Therapeutics — Investor Presentation (January 2026)
54 slides from Protagonist Therapeutics's investor presentation, Jan 12, 2026
Slide 1: Company Overview
COMPANY OVERVIEW Dinesh V. Patel, Ph.D. President & CEO January 12, 2026 1
Slide 2: Legal Disclaimer
Legal Disclaimer This presentation and any accompanying oral presentation contain forward - looking statements within the meaning of the Private Se curities Litigation Reform Act. All statements other than statements of historical facts contained in this presentation are forward - looking statements
Slide 3: Protagonist Therapeutics, Inc.
Protagonist Therapeutics, Inc. 3 • Biologically and commercially validated targets – Immunology & inflammation, hematology, and metabolic diseases • Strong differentiation vs existing therapies Integrated Discovery and Development Company With a Validated Technology Platform PN - 881 Oral IL - 17 An
Slide 4: Pipeline of Proprietary and Partnered Programs
Key Milestones Reg. Review Phase 3 Phase 2 Phase 1 Discovery/Preclinical → IND - Enabling Programs & Assets Pipeline of Proprietary and Partnered Programs INFLAMMATION & IMMUNOLOGY Icotrokinra Oral IL - 23R Peptide Antagonist Ulcerative Colitis Moderate - to - Severe Psoriasis ICONIC PsA - 1 & - 2 P
Slide 5: Multiple Near-Term Catalysts
Lead optimization/Pre - clinical: □ IL - 4R oral antagonist □ Amylin oral mono/poly - agonists □ Other programs Multiple Near - Term Catalysts 5 Two Potential Blockbuster Approvals, Multiple R&D Readouts & Strong Cash Position Commercial Value Drivers Multiple Clinical Programs I&I, Obesity and Hema
Slide 6: Icotrokinra JNJ and Protagonist Collaboration Economics
Icotrokinra 6 JNJ and Protagonist Collaboration Economics *Sensitivity analysis purposes only and does not represent management guidance, expectations or projections Expected Potential Development milestones through 2028 ~2026 $50M Receipt of marketing approval Any indication ~2027 $25M NDA filing a
Slide 7: Rusfertide Takeda and Protagonist Partnership Economics
Rusfertide 7 Takeda and Protagonist Partnership Economics Illustrative royalties during peak sales year (Opt - out Scenario) $3.5B $2.5B $1.5B $1.0B Annual net sales*** $0.9B $0.6B $0.3B $0.2B Pre - tax royalty receivable*** * $200M payable upon opt - out and a further $200M upon FDA approval **excl
Slide 8: Potential Sales Milestones: Icotrokinra and Rusfertide
Potential Sales Milestones: Icotrokinra and Rusfertide 8 Up to $1.2 Billion Receivable Icotrokinra Sales Milestones* Sales Milestone Calendar Year Net Sales $70M $1 Billion $95M $2 Billion $160M $3 Billion $100M $5 Billion $425M Total Potential Sales Milestones * All sales milestones EXCLUDED from c
Slide 9: Icotrokinra: Oral IL-23 Receptor Antagonist Peptide
Icotrokinra (JNJ - 2113, formerly PN - 235): Oral IL - 23 Receptor Antagonist Peptide Setting a new standard of treatment in plaque psoriasis & other IL - 23 mediated diseases J&J Partnership: 2017 to Present 9
Slide 10: Icotrokinra: First Oral IL-23R Therapy Targeting a >$80B Market
Icotrokinra: First Oral IL - 23R Therapy Targeting a >$80B 1 Market 10 >$10B 7 blockbuster potential Biologic - like efficacy and safety, with convenience of a once - daily pill WW market Size 2030 est. (7 - yr CAGR) 1 THE OPPORTUNITY of patients receiving SC/IV therapy and willing to switch to an o
Slide 11: Icotrokinra Clinical Development Program
Plaque Psoriasis Psoriatic Arthritis Ulcerative Colitis Crohn’s Disease Icotrokinra Clinical Development Program Psoriasis NDA submitted July’25; MAA submitted Sept’25 Successful Studies in Psoriasis & UC; PsA studies Ongoing; Phase 3 UC and CD studies underway ~Feb ‘27 ICONIC - PsA 2 10 Ph3, n ~ 75
Slide 12: Icotrokinra: Established Safety with Best-in-Class Oral Efficacy
Icotrokinra: Established Safety with Best - in - Class Oral Efficacy 12 ICONIC LEAD and ADVANCE Phase 3 Trial Results ICONIC LEAD NEJM Nov 2025; ICONIC AD VANCE 1&2 Lancet Sep 2025 PASI, Psoriasis Area and Severity Index. IGA, Investigator’s Global Assessment; • AE - related discontinuations similar
Slide 13: Icotrokinra Cross-Trial Comparison in UC: Clinical Response
Icotrokinra Cross - Trial Comparison to Phase 2 Benchmarks in UC 1 Clinical Response 13 64% 46% 61% 50% 51% 57% 0% 10% 20% 30% 40% 50% 60% 70% % Response Rate 1. Cross trial (not head - to - head) comparisons of unadjusted (ie, non - placebo adjusted) response data from phase 2 studies. 2. Icotrokin
Slide 14: Icotrokinra Cross-Trial Comparison in UC: Clinical Remission
Icotrokinra Cross - Trial Comparison to Phase 2 Benchmarks in UC 1 Clinical Remission 14 30% 10% 26% 20% 33% 16% 0% 5% 10% 15% 20% 25% 30% 35% % Response Rate 1. Cross trial (not head - to - head) comparisons of unadjusted (ie, non - placebo adjusted) remission data from phase 2 studies. 2. Icotroki
Slide 15: Icotrokinra Phase 3 UC and Phase 2/3 CD Clinical Studies
Icotrokinra Phase 3 Ulcerative Colitis (ICONIC - UC) and Phase 2b/3 Crohn’s Disease (ICONIC - CD) Clinical Studies 15 • Phase 3 ICONIC - UC study in adult and adolescent participants with moderately to severely active ulcerative colitis 1 : – Double - blind induction study in adults (co - primary en
Slide 16: Icotrokinra: Potential Commercial Launch in Psoriasis in 2026
Icotrokinra: Potential Commercial Launch in Psoriasis in 2026 followed by Multiple Indications Expansion in Coming Years 16 2028 2027 2026 2025 Setting ICONIC - PsA 1 Ph3, n~540, biologic - naive active ICONIC - PsA 2 Ph3, n~750, biologic exposed ICONIC - UC Ph3, n~882, in ulcerative colitis ICONIC
Slide 17: Rusfertide: Hepcidin Mimetic
17 Rusfertide: Hepcidin Mimetic Potential as a new practice changing standard of care in Polycythemia Vera (PV) PV: A rare myeloproliferative neoplasm characterized by excessive production of red blood cells 1 - Primary treatment goal is to maintain Hct <45% 2,3,4 , Polycythemia Vera. https://raredi
Slide 18: Polycythemia Vera Disease Background
Rare myeloproliferative neoplasm characterized by excessive production of red blood cells (RBCs) 1 Primary Treatment goal is to maintain Hct <45% 3,4 • Elevated hematocrit (Hct) >45% 2 Serious, chronic disease associated with increased thrombotic and cardiovascular risks 1 - 3 ~155,000 PV patients i
Slide 19: Unmet Need in PV and Hct Control
• Up to 78% of patients have uncontrolled Hct > 45% 2 • Thrombotic events (34 - 41%) 3 - 5 • Burdensome symptoms – Fatigue within last 12 months (73%) 6 – Full days in bed (23%) 6 – Iron deficiency (anemia) 7 1. Marchioli R, et al. N Engl J Med. 2013;368:22 - 33. 2. Verstovsek S, et al. Ann Hematol
Slide 20: Rusfertide Phase 3 VERIFY Study Results
Rusfertide Phase 3 VERIFY Study Results: PV 1,2 20 Durable, Sustained Hct Control With Fewer PHLs vs. Placebo, Addressing Major Unmet Need in PV 1,2 -1 0 1 2 3 Visit Week H e m a t o c r i t C h a n g e ( % ) BL 4 8 12 16 20 24 28 32 36 40 44 48 52 56 Rusfertide Placebo Placebo→Rusfertide Hct, hemat
Slide 21: Identifying PV Patients Who Will Benefit From Rusfertide
Identifying PV Patients Who Will Benefit From Rusfertide Defining patient population characteristics using current market treatments and trends is the key to understanding rusfertide's market opportunity Phlebotomy Frequency Dosing of Hydroxyurea Thrombotic Events Key indicators of suboptimal contro
Slide 22: Rusfertide: An RBC-Centric Treatment Option for PV
Rusfertide: An RBC - Centric Treatment Option for PV 22 Peak Revenue Potential of $1 - 2 Billion 3 ~155k diagnosed patients in the US with ~78k treated ~41k Phlebotomy (PHL) ~26k Hydroxy u rea (HU) ~6k Ruxolitinib ~3k Ropeg - interferon And/Or And/Or And/Or 1. Komodo Health closed claims dataset (20
Slide 23: Most PV Patients Experience Suboptimal Hct Control
Most Patients With Polycythemia Vera Experience Suboptimal Hct Control Frequent Phlebotomies, High - Dose Hydroxyurea and/or Post - Treatment TEs Are Common Komodo Health claims database (data from January 2016 to December 2022); includes patients who were ≥18 years old and had at lea st two clinica
Slide 24: Rusfertide: A Potential New Treatment Option for PV
Rusfertide 24 • PV is a rare myeloproliferative neoplasm characterized by excessive production of red blood cells 1 – Elevated hematocrit (Hct) >45% 2 – Primary treatment goal is to maintain Hct <45% 3,4 A Potential New Treatment Option For Polycythemia Vera References Key Milestones Phase 3 Phase 2
Slide 25: Rusfertide Improvements in Patient-Reported Outcomes vs Placebo
25 Rusfertide Led to Statistically Significant Improvements In Patient - Reported Outcomes (PROs) vs Placebo 1,2 **LS means (SE) difference (rusfertide – placebo); ***p - value associated with the LS mean difference. LS, least - squares; MFSAF TSS7, Myelofibrosis Symptom Assessment Form Version 4.0
Slide 26: Successful Completion of Phase 2 and 3 Studies
Rusfertide for Polycythemia Vera Successful Completion of Phase 2 and 3 Studies • Phase 2 REVIVE Study (N=70) 1 - 5 : – Randomized withdrawal data presented at EHA 2023 1 (late - breaking oral presentation); data published in NEJM 2 • Phase 2 PACIFIC Study (N=20) 7 : – High hematocrit (Hct >48%); 52
Slide 27: Rusfertide for PV: NDA Filing, Approval and Launch Timelines
Rusfertide for PV: NDA Filing, Approval and Commercialization Launch Timelines 27 2027 2026 2H 2025 Rusfertide for Polycythemia Vera ● NDA Submitted Dec ’25 Approval and Launch 2H ’26 Opt - out Decision Q2/Q3 ‘26 Potential FDA approval and commercial launch in 2H 2026 Rusfertide has Orphan Drug desi
Slide 28: R&D Pipeline: PN-881 Oral IL-17 Peptide Antagonist
R&D Pipeline I&I, Hematology, Obesity PN - 881: Oral IL - 17 Peptide Antagonist 28 Clinically and commercially validated target for multiple inflammatory conditions
Slide 29: Targeting a $17B+ Market with Oral IL-17 Inhibition
Targeting a $17B+ Market Opportunity with Differentiated ORAL IL - 17 Inhibition 29 • 31% of PsO market by 2031 • $17B+ opportunity currently dominated by injectables PN - 881: A Potential Best - in - Class Oral IL - 17A and F Antagonist 1. Psoriasis Disease Landscape and Forecast (Clarivate, 2023);
Slide 30: Criteria for Nomination of Oral PN-881 Development Candidate
Criteria for Nomination of Oral PN - 881 Development Candidate 1 Criteria Attribute x Sub - nM potency vs. IL - 17 AA x Blocks all dimeric forms of IL - 17: AA, AF, FF Potency x Stable in simulated gastric and intestinal fluids x Stable in serum with t 1/2 >24 hr x Metabolic stability x Thermostabil
Slide 31: PN-881 Potently Inhibits IL-17AA, AF, and FF
Neonatal Human Dermal Fibroblast (nHDF) and Human HT - 1080 Fibrosarcoma Cell Line (HT - 1080) IC 50 (nM) PN - 881 vs Injectables IL - 17 FF IL - 17 AF IL - 17 AA HT - 1080 nHDF HT - 1080 nHDF HT - 1080 nHDF 14 15 27 29 0.13 0.15 PN - 881 (Oral) Injectable Agents 13 14 19.5 18 0.17 0.12 Bimzelx ® In
Slide 32: PN-881 Achieves Desired Pharmacology in Preclinical Models
PN - 881 Achieves Desired Pharmacology in Preclinical Models • High systemic exposures after oral administration to mice, rats, dogs, and cynomolgus monkeys ▪ >100 ng/mL in cynomolgus monkeys with oral dose of 2.5 mg/kg • Blockade of IL - 17 in in vivo mouse models after oral administration – PN - 8
Slide 33: PN-881: Phase 1 Study in Healthy Volunteers
PN - 881: Comprehensive Phase 1 Study in Healthy Human Volunteers (N~142) 33 • Primary endpoint: – Incidence and severity of treatment - emergent adverse events (pre - dose to 7 days after last dose) • Secondary endpoints: – Pharmacokinetics and pharmacodynamics Part 3: Assessment of Solid Dose Form
Slide 34: PN-881: Near-Term Clinical Development Plan
PN - 881: Near - Term Clinical Development Plan 34 2H 2027 1H 2027 2H 2026 1H 2026 2H 2025 » Phase 2 HS Initiation » Phase 2 PsO Interim Analysis » Phase 2 PsO Initiation (Q4) » Phase 1 Topline Results » Phase 1 Initiation PN - 881 Oral IL - 17 Antagonist HS, hidradenitis suppurativa; PsO, plaque ps
Slide 35: PN-8047: An Oral Hepcidin Functional Mimetic
35 PN - 8047: An Oral Hepcidin Functional Mimetic Working towards a Hepcidin pathway based ORAL option in erythrocytosis mediated indications
Slide 36: PN-8047 Leverages Our Expertise in the Hepcidin Pathway
PN - 8047: Oral Hepcidin Functional Mimetic 36 Leverages Our Expertise in the Hepcidin Pathway Rusfertide established hepcidin mimetics as a therapeutic option for polycythemia vera Clinical validation of hepcidin biology PN - 8047: a wholly owned asset that builds on Protagonist’s knowledge base of
Slide 37: PN-8047: Oral Hepcidin Functional Mimetic for Targeting PV
PN - 8047: An Oral Hepcidin Functional Mimetic for Targeting Polycythemia Vera 37 Human - FPN Potency EC 50 (nM) 13.7 Hepcidin 2.5 Rusfertide 4.3 PN - 8047 Table shows average values for effective concentration for 50% signal (EC 50 ) in nano - molar (nM) Human - FPN assay measured functional respon
Slide 38: PN-8047: Potent with Excellent PK, PD, and Efficacy Properties
PN - 8047: Novel Oral Small Molecule that is Potent with Excellent PK, PD, and Efficacy Properties 38 Summary of PN - 8047 Properties Attributes x Nanomolar potency in the T47D - TfR1 functional assay x Similar potency as Rusfertide Potency x Metabolically stable in liver microsomal incubations x Go
Slide 39: PN-8047 Development Timelines
PN - 8047: Oral Hepcidin Functional Mimetic Development Timelines 39 *PK - and PD (serum iron reduction) - based clinical PoC 2H 2027 1H 2027 2H 2026 1H 2026 » Phase 2 Initiation » Topline results from Phase 1* » Phase 1 Initiation » IND - enabling studies PN - 8047
Slide 40: Anti-Obesity Therapeutics
Anti - Obesity Therapeutics: Dominated by injectable appetite - suppressing hormone peptide mimetics Oral Peptide agents offer a strong differentiation and address unmet medical need 40
Slide 41: Obesity: Unprecedented Pharmaceutical Opportunity
Obesity: Unprecedented Pharmaceutical Opportunity in the US and Worldwide • Obesity is a global epidemic – In 2024, nearly 40% of Americans were obese or considered drug - eligible overweight 1 • Current challenges with anti - obesity drugs 1 – Convenience; needle avoidance – Early days & limited op
Slide 42: Desirable Features for Next Generation Anti-Obesity Candidate
Desirable Features for Next Generation Anti - Obesity Candidate An ORAL Triple - Agonist Peptide (GLP - 1R/GIPR/GCGR) • Potential improvements – Oral option – Magnitude of body weight loss ▪ Potential secondary benefits in co - morbidities (diabetes, CVD, OSA, CKD, MASH etc.) – Improving tolerabilit
Slide 43: PN-477: A Novel Triple GLP/GIP/GCG Receptors Agonist Peptide
PN - 477: A Novel Triple GLP/GIP/GCG Receptors Agonist Peptide 43 Optionality for Oral or Subcutaneous Dosing ORAL Triple - Agonist Once - daily Dosing Injectable Triple - Agonist Once - weekly Dosing PN - 477sc PN - 477o Potential Improvements • Magnitude and quality of body weight loss – Potential
Slide 44: PN-477 Oral Triple Agonist Peptide Criteria
PN - 477 Oral Triple Agonist (GLP - 1R, GIPR, GCGR) Peptide 44 Criteria Attribute x nM potency vs GLP - 1R, GIPR, GCGR Potency x Stable in simulated gastric and intestinal fluids x Stable in serum x Metabolic stability x Thermostability Stability x Mouse Diet Induced Obesity (DIO) model Efficacy Mod
Slide 45: Oral PN-477o and Subcutaneous PN-477sc DIO Mice Study
Oral PN - 477o and Subcutaneous PN - 477sc DIO Mice Study #1 % Body Weight Change, SC: Days 1 - 14 1 2 3 4 5 6 7 8 9 1011121314 -60 -50 -40 -30 -20 -10 0 Days B o d y W e i g h t C h a n g e ( % ) Vehicle Control (SC, Q3D) Retatrutide ( SC 30 nmol/kg, Q3D*) PN - 477sc (SC 30 nmol/kg, Q3D) 4.4 39.7 4
Slide 46: PN-477: A Potential Best-in-Class Triple Agonist
PN - 477: A Potential Best - in - Class Triple Agonist Anti - Obesity Peptide Development Candidate with Convenience of Once - Daily Oral and Once - Weekly SC Dosing • Novel, orally stable, and potent triple agonist (GLP - 1R, GIPR, and GCGR) • Engineered balance of GLP - 1R, GIPR, GCGR absolute and
Slide 47: PN-477: Near-Term Clinical Development Plan
PN - 477: Near - Term Clinical Development Plan 47 2H 2027 1H 2027 2H 2026 1H 2026 » Topline results from Phase 1 (o) » Topline results from Phase 1 (sc)** » Phase 1 Initiation (o) » IND - enabling studies » Phase 1 Initiation (sc) PN - 477sc and PN - 477o* Anti - Obesity *PN - 477sc weekly sc dosin
Slide 48: PN-458: A Highly Potent Oral Dual GLP-1/GIP Receptor Agonist
PN - 458: A Highly Potent Oral Dual GLP - 1/GIP Receptor Agonist 48 • PN - 458 is higher potency than Tirzepatide for GLP - 1R and GIPR • Higher GIPR potency may be favorable for better GI tolerability 4,5 Potential Weight Loss Profile and GI Tolerability of Tirzepatide Human EC 50 (nM) GCGR GIPR GL
Slide 49: PN-458 Dual Agonist Peptide Criteria
PN - 458 Dual Agonist (GLP - 1R, GIPR) Peptide 49 Criteria Attribute x nM potency vs GLP - 1R, GIPR Potency x Stable in simulated gastric and intestinal fluids x Stable in serum x Metabolic stability x Thermostability Stability x Mouse Diet Induced Obesity (DIO) model Efficacy Model x Glucose contro
Slide 50: PN-458: A Potential Best-in-Class Dual Agonist
PN - 458: A Potential Best - in - Class Dual Agonist Anti - Obesity Peptide Development Candidate with Convenience of Once - Daily Oral and Once - Weekly SC Dosing 50 • Novel, orally stable, and potent dual agonist (GLP - 1R and GIPR) • Engineered balance of GLP - 1R and GIPR absolute and relative p
Slide 51: Building a Portfolio of Oral and Injectable Anti-Obesity Agents
Building a Portfolio of ORAL and Injectable Anti - Obesity Agents 51 PN - 458: A Dual GLP - 1R/GIPR Oral & SC Agonist • Tirzepatide (Zepbound ® ): The only approved dual GLP - 1R/GIPR therapy – Best - in - class: Body weight loss ~20.2% 1 – Best - selling anti - obesity drug – Injectable • PN - 458
Slide 52: Protagonist Therapeutics: What's Next?
Protagonist Therapeutics What’s Next?
Slide 53: Major Upcoming Catalysts in 2026-2027
Major Upcoming Catalysts in 2026 - 2027 53 Expected Clinical Trial Initiations, Data Readouts, and Development Candidate Nominations 2027 2H 2026 1H 2026 PN - 8047* PN - 458sc* PN - 458o* PN - 477sc* PN - 477o* PN - 881* Icotrokinra Rusfertide Discovery* *Fully owned by Protagonist Therapeutics, Inc
Slide 54: Thank you
Protagonist Therapeutics Thank you
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