Protagonist Therapeutics, Inc. · NASDAQ:PTGX
Protagonist Therapeutics — Investor Presentation (August 2026)
49 slides from Protagonist Therapeutics's investor presentation, Aug 5, 2026
Slide 1: Company Overview
COMPANY OVERVIEW Dinesh V. Patel, Ph.D. President & CEO August 5, 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 statemen t
Slide 3: Protagonist Therapeutics: Revenue Engine and Pipeline
Commercial & Partnered Inflammation & Immunology Metabolic ICOTYDE ( icotrokinra ) Oral IL - 23R Antagonist • Partner: J&J FDA Approved: Mar ’26 EMA CHMP Positive Opinion: Jul ’26 Moderate - to - Severe Plaque Psoriasis 6 – 10% royalties + milestone payments >$10B peak potential 1 Rusfertide SC Hepc
Slide 4: Protagonist Partnership Economics Expected to Finance Our R&D Pipeline
ICOTYDE (icotrokinra); Oral IL - 23R Antagonist; Partner: J&J $387.5M Payments received $580M Future milestones 6 – 10% Tiered worldwide royalties >$10B 1 ICOTYDE peak sales potential FDA Approved Mar ’26 (Mod to Sev Plaque PsO ) · PsA Ph3 · UC Ph3 · CD Ph2/3 · EMA CHMP positive opinion: Jul ’26 7.2
Slide 5: Protagonist Partnership Economics (cont'd)
ICOTYDE (icotrokinra); Oral IL - 23R Antagonist; Partner: J&J Rusfertide ; SC Hepcidin Mimetic; Partner: Takeda Significant royalties and up to $1.63B in future milestone payments Protagonist Partnership Economics (cont’d) Expected to Finance Our R&D Pipeline and Potential Capital Return * Sensitivi
Slide 6: Multiple Programs With Significant Value Creation Over the Next 24 Months
PROGRAM THERAPEUTIC AREA STAGE / STATUS VALUE INFLECTION ICOTYDE Oral IL - 23R I&I Approved for Mod to Sev Plaque PsO Launch trajectory Ph2 and Ph3 readouts Rusfertide Hepcidin mimetic Hematology FDA review (NDA for PV) FDA decision (PDUFA: Aug ’26) PN - 881 Oral IL - 17A/F I&I Ph1; Ph2b PsO Ph1 saf
Slide 7: Business Overview: Protagonist Therapeutics
Protagonist Therapeutics 7 • Commercial and Late - Stage Assets – ICOTYDE – Rusfertide • De - risked Strategy and Strengthened Pipeline – De - risked targets (e.g., IL - 17, IL - 4, hepcidin, incretin, glucagon and amylin) – Validated platform and approach (ICOTYDE, rusfertide) • Accelerated Path to
Slide 8: ICOTYDE (icotrokinra): Targeted Oral IL-23 Receptor Antagonist Peptide
ICOTYDE (icotrokinra; JNJ - 2113, formerly PN - 235): Targeted Oral IL - 23 Receptor Antagonist Peptide Setting a new standard of treatment in moderate to severe plaque psoriasis and other IL - 23 mediated diseases J&J Partnership: 2017 to Present 8 ICOTYDE is a trademark of Johnson & Johnson and it
Slide 9: ICOTYDE: First Oral IL-23R Therapy Targeting >$80B Market
ICOTYDE (icotrokinra): First Oral IL - 23R Therapy Targeting >$80B 1 Market 9 >$10B 7 blockbuster potential Established efficacy and proven safety profile in 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 10: ICOTYDE (icotrokinra) J&J Partnership Overview
ICOTYDE (icotrokinra) 10 • Johnson & Johnson partnership overview – 2017 to present – Protagonist completed pre - clinical and first Ph1 study 1 – J&J responsible for further development and commercialization • ICOTYDE is the first and only IL - 23R targeted oral peptide to – clear skin for moderate
Slide 11: Icotrokinra Potential Expansion of Multiple Indications in Coming Years
Icotrokinra Potential Expansion of Multiple Indications in Coming Years 11 2028 2027 2026 2025 Setting ICONIC - PsA 1 Ph3, n = 552, biologic - naive active ICONIC - PsA 2 Ph3, n~750, biologic exposed ICONIC - UC Ph3, n~882, in ulcerative colitis ICONIC - CD Ph 2/3, n~1092, in Crohn’s disease ICONIC
Slide 12: Icotrokinra Cross-Trial Comparison to Phase 2 Benchmarks in UC
10% 26% 20% 33% 16% 0% 5% 10% 15% 20% 25% 30% 35% % Response Rate Icotrokinra Cross - Trial Comparison to Phase 2 Benchmarks in UC 1 30% 0% 5% 10% 15% 20% 25% 30% 35% % Response Rate Clinical Remission 12 1. Cross trial (not head - to - head) comparisons of unadjusted (ie, non - placebo adjusted) re
Slide 13: Rusfertide: A Potential Practice-Changing, New Standard-of-Care in Polycythemia Vera
13 Rusfertide: A Potential Practice - Changing, New 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. 1. https://rarediseases.org
Slide 14: Unmet Need in Polycythemia Vera; 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 15: Rusfertide Phase 3 VERIFY Study Results: PV
Rusfertide Phase 3 VERIFY Study Results: PV 1,2 15 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 16: Rusfertide: An RBC-Centric Treatment Option for PV
Rusfertide: An RBC - Centric Treatment Option for PV 16 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 17: Most Patients With PV 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 18: Rusfertide for PV: NDA Filing, Approval and Launch Timelines
Rusfertide for PV: NDA Filing, Approval and Commercialization Launch Timelines 18 FDA Granted Rusfertide NDA Priority Review in March 2026 2027 2026 2H 2025 Rusfertide for Polycythemia Vera ● NDA Submitted Dec ’25 Potential Approval and Launch Aug ’26 1 Opted - out Apr ’26 Potential FDA approval and
Slide 19: R&D Pipeline: PN-881 Oral IL-17A and IL-17F Antagonist
R&D Pipeline I&I, Hematology, Obesity PN - 881: A Potential Best - in - Class Oral IL - 17A and IL - 17F Antagonist Clinically and commercially validated target for multiple inflammatory conditions
Slide 20: Targeting a $17B+ Market Opportunity with Oral IL-17 Inhibition
Targeting a $17B+ Market Opportunity with Differentiated ORAL IL - 17 Inhibition 20 • 30 % of PsO market by 2034 • $17B+ opportunity currently dominated by injectables PN - 881: A Potential Best - in - Class Oral IL - 17A and IL - 17F Antagonist 1. Psoriasis Disease Landscape and Forecast (Clarivate
Slide 21: Criteria for Nomination of Oral PN-881 Development Candidate
Criteria for Nomination of Oral PN - 881 Development Candidate 1 21 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 Thermosta
Slide 22: PN-881 Achieved Desired Pharmacology in Preclinical Models
PN - 881 Achieved 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 23: PN-881: Comprehensive Phase 1 Study in Healthy Volunteers
PN - 881: Comprehensive Phase 1 Study in Healthy Volunteers (N~142) 23 • Primary endpoint: – Incidence and severity of treatment - emergent adverse events (pre - dose to 7 days after last dose) • Secondary endpoint: – Pharmacokinetics Phase 1 Study Completed Part 3: Assessment of Solid Dose Formulat
Slide 24: PN-881 Potently Inhibits Both IL-17A and IL-17F Isoforms
PN - 881 Potently Inhibits Both IL - 17A and IL - 17F Isoforms 24 Neonatal Human Dermal Fibroblast IL - 17AA+IL - 17FF 2 IL - 17FF 1 IL - 17AA 1 IC 90 (nM) IC 50 (nM) IC 90 (nM) IC 50 (nM) IC 90 (nM) IC 50 (nM) 0.098 0.013 0.124 0.015 0.031 0.0026 Oral Peptide, PN - 881 0.071 0.015 0.037 0.014 0.003
Slide 25: PN-881: Phase 1 Pharmacokinetic Results
25 • Achieved 24 - hour C trough levels significantly higher than prospectively targeted IC 90 (IL - 17AA, IL - 17FF, IL - 17AA+FF) values with once - daily oral dosing • Drug accumulation results in higher drug levels at steady state (data not shown) • Generally well tolerated; no serious adverse e
Slide 26: PN-881: Clinical Development Plans in Psoriasis and Other Indications
PN - 881: Successful Ph1 Lays a Strong Foundation for Comprehensive Ph2b Program 26 Clinical Development Plans in Psoriasis and Other Potential Indications 1H 2028 2H 2027 1H 2027 2H 2026 » Potential Ph2 HS initiation » Ph2b PsO topline » Ph2b PsO enrollment completion » Ph2b PsO study initiation (e
Slide 27: PN-8047: An Oral Hepcidin Functional Mimetic
27 PN - 8047: An Oral Hepcidin Functional Mimetic Working towards a Hepcidin pathway based ORAL option in polycythemia vera
Slide 28: PN-8047: Oral Hepcidin Functional Mimetic Leveraging Our Hepcidin Expertise
PN - 8047: Oral Hepcidin Functional Mimetic 28 Leveraging Our Expertise in the Hepcidin Pathway Rusfertide established hepcidin mimetics as a therapeutic option for polycythemia vera Clinical validation of hepcidin biology PN - 8047: Builds on Protagonist’s knowledge base of hepcidin pathway
Slide 29: PN-8047: Oral Hepcidin Functional Mimetic for Targeting PV
PN - 8047: An Oral Hepcidin Functional Mimetic for Targeting Polycythemia Vera 29 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 30: PN-8047: Novel Potent Oral Small Molecule With Excellent PK, PD, and Efficacy
PN - 8047: Novel Potent Oral Small Molecule With Excellent PK, PD, and Efficacy Properties 30 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 Good perme
Slide 31: PN-8047: Development Timelines
PN - 8047: Oral Hepcidin Functional Mimetic Development Timelines 31 *PD (serum iron reduction) - based clinical PoC 2H 2027 1H 2027 2026 » Initiate Ph2 PV study » Ph1 Initiation (Q1 ’27) » Ph1 PD Clinical PoC* » IND - enabling studies PN - 8047
Slide 32: Metabolic Pipeline: Unimolecular Oral Anti-Obesity Therapies
Metabolic Pipeline: Addressing the Need For Unimolecular Oral Anti - Obesity Therapies Triple - G, Dual - G, and AmylinR Agonists
Slide 33: Obesity: Unprecedented Pharmaceutical Opportunity in the US and Worldwide
Obesity: Unprecedented Pharmaceutical Opportunity in the US and Worldwide Only ~5% of Eligible Patients Receive Drug Treatment 1 131 million Obese and d rug - eligible overweight population in the US 1 ~6 - 7 million US pa tients t reated 2 1 Clarivate Disease Landscape & Forecast – Obesity/Overweig
Slide 34: Four of the Current Top 10 Best-Selling Drugs are Peptide-Based Therapies
2015 1 peptide branded therapy in top 10 Humira $14.0B mAb Harvoni $13.9B SM Enbrel $8.7B Fusion Remicade $8.4B mAb Rituxan $7.1B mAb Lantus $7.0B Peptide Avastin $6.8B mAb Herceptin $6.6B mAb Revlimid $5.8B SM Sovaldi $5.3B SM → 2025 Keytruda $31.7B mAb Mounjaro $23.0B Peptide Ozempic $19.2B Peptid
Slide 35: PN-477: A Novel Triple GLP-1/GIP/GCG Receptor Agonist Peptide
PN - 477: A Novel Triple GLP - 1/GIP/GCG Receptor Agonist Peptide 35 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 – Potent
Slide 36: PN-477: Oral Triple Agonist Peptide
PN - 477 Oral Triple Agonist (GLP - 1R, GIPR, GCGR) Peptide 36 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 37: PN-477 is More Potent than Retatrutide
PN - 477 is More Potent than Retatrutide 37 • cAMP assay: PN - 477 is more potent than retatrutide for GLP - 1R and GIPR – GLP - 1R : GIPR potency ratio for PN - 477 is similar to tirzepatide ‡ Sourced from MCE Cat. HY - 114118 (Semaglutide); 1PlusChem Cat. 1P01MVTY (Tirzepatide); MCE Cat. HY - P350
Slide 38: Oral and Subcutaneous PN-477 Promote Significant Body Weight Loss
Oral and Subcutaneous PN - 477 Promote Significant Body Weight Loss 38 Pre - Clinical Efficacy Study Using DIO Mice % 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 nm
Slide 39: BW Loss in Normal Cynomolgus Monkeys after Oral Dosing of PN-477
11% BW Loss by Day 7 in Normal Cynomolgus Monkeys after 7 - Day Oral Dosing of PN - 477 39 Weight Loss Sustained for 6 Days After Last Dose 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Time (Day) - 15 - 10 - 5 0 Body Weight (% Change) - 10% - 11% % BW Change, PO PK C trough Day 1 - 7 , PO Last dose on Day 7 Sus
Slide 40: BW Loss in Cynomolgus Monkeys after Single SC Dose of PN-477
1 2 3 6 7 4 5 Time (Day) - 15 - 10 - 5 0 Body Weight (% Change) Retatrutide (0.36 mg/kg) PN - 477 (0.30 mg/kg) - 7% - 13% 13% BW Loss Normal Cynomolgus Monkeys by 7 - Days Post - Single SC Dose of PN - 477 40 1 2 3 4 1 10 100 1000 10000 Time (Day) Concentration in Plasma (ng/mL) Retatrutide (0.36 mg
Slide 41: BW Loss in Normal Beagle Dogs after Single SC Dose of PN-477
10% BW Loss by Day 11 in Normal Beagle Dogs after Single SC Dose of PN - 477 41 1 2 5 6 3 4 Time (Day) 1 10 100 1000 10000 Concentration in Plasma (ng/mL) Retatrutide (0.36 mg/kg) PN - 477 (0.30 mg/kg) 1 2 3 4 5 6 7 8 9 10 11 Time (Day) - 15 - 10 - 5 0 Body Weight (% Change) Retatrutide (0.36 mg/kg)
Slide 42: PN-477: A Potential Best-in-Class Triple Agonist Anti-Obesity Peptide
PN - 477: A Potential Best - in - Class Triple Agonist Anti - Obesity Peptide 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 relative potencies –
Slide 43: PN-477: Near-Term Clinical Development Plan
PN - 477: Near - Term Clinical Development Plan 43 2H 2027 1H 2027 2026 □ PN - 477sc Ph1b MAD PoC □ PN - 477sc Ph1b MAD (13 weeks) initiation □ PN - 477sc Ph1 SAD initiated (Q3 ’26) PN - 477sc* Anti - Obesity *PN - 477sc: weekly sc dosing; PN - 477o: once - daily oral dosing 2H 2027 1H 2027 2026 □ P
Slide 44: PN-458: A Highly Potent Oral Dual GLP-1/GIP Receptor Agonist
PN - 458: A Highly Potent Oral Dual GLP - 1/GIP Receptor Agonist 44 • PN - 458 has higher potency than tirzepatide for GLP - 1R and GIPR Potential Weight Loss Profile and GI Tolerability of Tirzepatide Human EC 50 (nM) GCGR GIPR GLP - 1R NA † 1.7 23.1 Tirzepatide 1,‡ (Eli Lilly Dual GLP - 1R/GIPR) N
Slide 45: PN-458: Oral Dual Agonist Peptide
PN - 458 Dual Agonist (GLP - 1R, GIPR) Peptide 45 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 46: Two Anti-Obesity Assets Create Strategic Flexibility
PN - 477 TRIPLE AGONIST GLP - 1 / GIP / GCG agonist peptide DESIGN GOAL Maximize weight loss magnitude and quality (preferential fat mass loss) BENCHMARK Retatrutide - class profile FORMATS Once - daily oral, once - weekly SC PRECLINICAL Significant body weight loss in DIO mice, dogs, and cynomolgus
Slide 47: What's Next?
Protagonist Therapeutics What’s Next?
Slide 48: Expected Clinical Trial Initiations, Data Readouts, and Development Candidate Nominations
Protagonist Therapeutics 48 Expected Clinical Trial Initiations, Data Readouts, and Development Candidate Nominations *Wholly - owned by Protagonist Therapeutics, Inc . DC, Development candidate, ready for IND - enabling studies; IND, investigational new drug; MAD, multiple ascending dose; NDA, new
Slide 49: Thank you
Protagonist Therapeutics Thank you
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