Protagonist Therapeutics, Inc. · NASDAQ:PTGX

Protagonist Therapeutics — Technical Presentation (February 2025)

57 slides from Protagonist Therapeutics's technical presentation, Feb 6, 2025

  1. Slide 1: Polycythemia Vera (PV) Day

    Polycythemia Vera (PV) Day Thursday 6 February 2025 Dinesh Patel, Ph.D. Director, President, and CEO Protagonist Therapeutics, Inc. Newark, CA 1

  2. Slide 2: Forward-looking Statements

    Forward-looking Statements This presentation and the accompanying oral presentation contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this prese

  3. Slide 3: Peptide Therapeutics Company

    Peptide Therapeutics Company Two Late-Stage Assets with Potential for NDA Filings in 2025 • Biologically and commercially validated targets – Immunology & Inflammation, hematology, and metabolic diseases • Protagonist Peptides offer strong differentiation vs existing therapies Peptide Technology Pla

  4. Slide 4: Major Upcoming Catalysts in 2025

    Major Upcoming Catalysts in 2025 Expected Clinical Trial Initiations, Data Readouts and Development Candidate Nominations 2024 Q1 2025 Q2 2025 Q4 2025  New Engl J Med, 2024;  PV day (Feb 6th) 390:723-35, REVIVE Ph2 Rusfertide  Ph3 VERIFY enrollment  Topline  NDA filing completion results (Mar)

  5. Slide 5: Forecast Cash Runway And Potential Sources of Future Cash Inflows

    Forecast Cash Runway And Potential Sources of Future Cash Inflows Current financial resources extend through at least end of Q4 2028 2025 2026 2027 2028 Beyond 2028 Cash runway through at least end of 2028 $583M in cash, equivalents and marketable securities as of September 30, 2024 + $165M JNJ mile

  6. Slide 6: Thank you

    & Protagonist Therapeutics Thank you

  7. Slide 7: PV Day: Agenda and Overview

    PV Day: Agenda and Overview Arturo Molina, MD, MS, FACP Chief Medical Officer Protagonist Therapeutics, Inc. Newark, CA 7

  8. Slide 8: Agenda

    Agenda Item Duration Time (EST) Presenter(s) Dinesh Patel, PhD and Welcome and Introduction 10 10:30 – 10:40 am Arturo Molina, MD, MS, FACP PV Overview and Symptomology 10 10:40 – 10:50 am Joseph M. Scandura, MD, PhD Review of Phase 2 PACIFIC Data 10 10:50 – 11:00 am Arturo Molina, MD, MS, FACP Revi

  9. Slide 9: PV Day: Objectives

    PV Day: Objectives • Provide a high-level overview of: – Polycythemia vera (PV) and clinical signs and symptoms of PV – Common treatment options for patients with PV, including therapeutic phlebotomy, low- dose aspirin, and cytoreductive therapy – The phase 2 PACIFIC and REVIVE clinical studies that

  10. Slide 10: Rusfertide: Clinical Development in Patients with Polycythemia Vera

    Rusfertide: Clinical Development in Patients with Polycythemia Vera Disc./Pre-Clinical Phase 1 Phase 2 Phase 3 Key Milestones Polycythemia Vera (PV) HEMATOLOGY VERIFY Ph 3, n~250 • Top-line 32-Wk Primary EP results March‘25 RUSFERTIDE REVIVE Ph 2, n=70 • Study completed; OLE ongoing Hepcidin Mimetic

  11. Slide 11: Phase 3 VERIFY Study is a Global Trial

    Phase 3 VERIFY Study is a Global Trial N~250 Patients (19 Countries) Enrolled in VERIFY; 70 Patients (2 Countries) Enrolled in REVIVE Europe Austria, Belgium, Czechia, France, Germany, Hungary, Italy, Netherlands, Poland, Portugal, Spain, UK Canada United States Turkey Israel India Hong Kong Mexico

  12. Slide 12: Polycythemia Vera (PV): Overview and Symptomology

    Polycythemia Vera (PV): Overview and Symptomology Joseph M. Scandura, MD, PhD Associate Professor of Medicine Weill Cornell Medicine New York, New York 12

  13. Slide 13: Polycythemia Vera (PV) is a disease of too many Red Blood Cells (RBCs)

    Polycythemia Vera (PV) is a disease of too many Red Blood Cells (RBCs) PV is a rare, chronic myeloproliferative neoplasm Vascular Sludging & Irritation A vascular traffic jam • Symptoms • Excess clotting • Shortened survival Image created in https://BioRender.com. Accessed on 29 January 2025. 13

  14. Slide 14: PV Affects Working-age Patients, Reducing Lifespan and Quality of Life

    PV Affects Working-age Patients, Reducing Lifespan and Quality of Life Total cases (USA)1: Median age at diagnosis2: ~155,000 61 years old % of PV patients with Average Life Expectancy JAK2 alteration3: Post-diagnosis4: >95+% ~16 years 1. Data on File. Protagonist Therapeutics, Inc., January 2025; 2

  15. Slide 15: Most patients with Polycythemia Vera Report Bothersome Symptoms

    Most patients with Polycythemia Vera Report Bothersome Symptoms Symptoms Include*,1-5: Symptoms Related to Iron • Excessive sweating/night sweats (25-67%) Deficiency*: • Early satiety (feeling full) (20-61%) • Fatigue (36-82%) • Abdominal discomfort (8-51%) • Dizziness (25-64%) • Bone pain (23-48%)

  16. Slide 16: MPNs and PV Increase Risk of Second (Non-PV) Cancers

    MPNs and PV Increase Risk of Second (Non-PV) Cancers Skin cancers are increased in MPNs, PV and in those using hydroxurea (HU) and ruxolitinib1-4 Increased risk of HU-treated PV non-hematologic patients had malignancies in MPN patients ~2× the rate compared to of skin cancers matched controls:1 comp

  17. Slide 17: Patients with PV have much higher risk for medically dangerous clotting events

    Patients with PV have much higher risk for medically dangerous clotting events Clotting risk is highest around diagnosis but is always several times higher than normal1. Artery Clots Vein Clots Heart attacks, strokes DVT/PE PV, polycythemia vera; TE, thromboembolic event. 1. Hultcranz, M., et al. An

  18. Slide 18: PV Blood Clot Risk Is Reduced by Control of Hematocrit

    PV Blood Clot Risk Is Reduced by Control of Hematocrit Important to Maintain Consistent Hematocrit (Hct) Control <45% ~4× increased risk of CV death and major thrombosis in PV patients with (uncontrolled) Hct (CYTO-PV study)1 CV, cardiovascular; Hct, hematocrit; PV, polycythemia vera; TE, thromboemb

  19. Slide 19: How Do We Treat Polycythemia Vera?

    How Do We Treat Polycythemia Vera? Manage cardiovascular risk factors Low-dose Aspirin *Indications for Cytoreductive Therapy: Frequent phlebotomy required Hct ≥ Intolerance to phlebotomy 45% Symptoms Add Thrombosis risk Thrombotic event Cytoreductive Therapy* Yes Phlebotomy (PHL) Cytoreductive Ther

  20. Slide 20: Phlebotomy Is Inadequate in Reducing Thrombotic Risk

    Patients with PV have much higher risk for medically dangerous clotting events Clotting risk is highest around diagnosis but is always several times higher than normal1. Phlebotomy, Even with Concomitant Cytoreductive Therapy, Is Inadequate in Reducing Thrombotic Risk Vein Clots DVT/PE ≥3 PTB/year (

  21. Slide 21: In patients with PV, almost all total body iron is in red blood cells

    In patients with PV, almost all total body iron is in red blood cells (RBCs) All cells in the body use iron to generate energy. Phlebotomy literally throws out the total body iron... 21

  22. Slide 22: Iron Deficiency Can Cause Symptoms in Patients with Polycythemia Vera

    Iron Deficiency Can Cause Symptoms in Patients with Polycythemia Vera Muscles PV is Associated With Symptoms and That Vary in Brain Need Severity Iron to Relative too... Myelofibrosis5-8 Symptoms Include*: Symptoms Related to Iron • Excessive sweating/night sweats (25-67%) Deficiency*: • Early satie

  23. Slide 23: Adherence to Treatment Standards in PV is Critical for Survival

    Adherence to Treatment Standards in PV is Critical for Survival Phlebotomy is time-consuming, requires infrastructure and costs $$ Average life expectancy post-diagnosis4: ~16 years As a rare disease, standards of PV therapy are not always followed in the community. 1. Data on File. Protagonist Ther

  24. Slide 24: PV Cheats the Body of Iron to Make RBCs Nobody Needs

    PV Cheats the Body of Iron to Make RBCs Nobody Needs… Normal PV Give Me Your Iron! Suppress Hepcidin 24

  25. Slide 25: Hepcidin Is the Master Regulator of Iron

    Hepcidin Is the Master Regulator of Iron Rusfertide is a Hepcidin Mimetic That Prevents Excessive RBC Production in the Bone Marrow PV: Excessive Production of RBCs Hepcidin Mimetic: Mechanism of Action 1 Rusfertide binds FERROPORTIN RUSFERTIDE Normalized FERROPORTIN Elevated to ferroportin, 3 Hct (

  26. Slide 26: Phase 2 PACIFIC Study: Design and Key Results

    Phase 2 PACIFIC Study: Design and Key Results Arturo Molina, MD, MS, FACP Chief Medical Officer Protagonist Therapeutics, Inc. Newark, California 26

  27. Slide 27: Phase 2 PACIFIC Study: Rusfertide in PV Patients with High Hct (>48%)

    Phase 2 PACIFIC Study: Rusfertide in PV Patients with High Hct (>48%)1,2 Open-Label Study Design (NCT04767802) and Key Eligibility Criteria Rusfertide (up to 52 weeks) Key Eligibility: Dose Finding (N=20) Dose ± titration*: • Conducted in Malaysia and S. Korea Starting Dose: • No phlebotomy or cytor

  28. Slide 28: Rapid Hematocrit Control <45% Was Achieved in <5 Weeks

    Phase 2 PACIFIC Study: Rusfertide in PV Patients with High Hematocrit (>48%)1,2 Rapid Hematocrit Control <45% Was Achieved in <5 Weeks • Median time to first Hct <45%: 4.93 weeks • Rate of Hct Reduction: 1.7%/week • Proportion with Hct <45% before study entry: 0% • Proportion with Hct <45% at Week 8

  29. Slide 29: PACIFIC Safety Profile

    Phase 2 PACIFIC Study: Rusfertide in PV Patients with High Hematocrit (>48%)1 Safety Profile in PACIFIC Consistent With Observations in Phase 2 REVIVE Study • The most common all-grade TEAEs were All-grade TEAES (≥10% of All Participants injection-site reactions Patients), continued n (%) (N=20) • N

  30. Slide 30: PACIFIC Study Summary

    Phase 2 PACIFIC Study: Rusfertide in PV Patients with High Hematocrit (>48%) Summary • Rusfertide resulted in a rapid reduction in Hct levels – Median time to achieve Hct <45% was <5 weeks – 85% of patients achieved Hct levels <45% within 8 weeks • Improved control of Hct resulted in a significant r

  31. Slide 31: Phase 2 REVIVE Study: Design and Key Results

    Phase 2 REVIVE Study: Design and Key Results Andrew Kuykendall, MD Associate Member Moffitt Cancer Center Tampa, Florida 31

  32. Slide 32: Phase 2 REVIVE Study of Rusfertide in PV

    Phase 2 REVIVE Study of Rusfertide in PV REVIVE THRIVE 1:1 Randomized Long Term Extension Dose Finding Open Label Extension Inclusion Criteria Withdrawal ≥3 PHL (28 wks prior) PART 1 (28 wks) PART 2 (up to 12 wks) PART 3 (up to 3 years) Additional 2 years 70 Pts 59 Pts 58 Pts of treatment with or wi

  33. Slide 33: REVIVE Parts 1 and 3: Demographics and Disease Characteristics

    REVIVE Parts 1 and 3: Demographics and Disease Characteristics1-5 REVIVE • 70 patients enrolled into Part 1 N=70 Age (years), median (range) 58 (27-77) • 59 patients (30, rusfertide; 29, placebo) Gender, n (%) enrolled into the randomized withdrawal phase Male 49 (70.0) (Part 2) Female 21 (30.0) • 5

  34. Slide 34: REVIVE Met the Primary Efficacy Endpoint

    REVIVE Met the Primary Efficacy Endpoint in the Prespecified Full Analysis and Randomized Analysis Populations (Part 2) • Data from sensitivity analysis demonstrates that primary endpoint is robust1,2 • Data Published in New Engl J Med1; • Final Study Data (Including OLE) Presented at 2024 ASH Meeti

  35. Slide 35: Phase 2 REVIVE Study: Clinical Efficacy

    Phase 2 REVIVE Study: Clinical Efficacy Rusfertide Provided Rapid, Robust, and Durable Control of Hct • Hct control <45% Randomized Withdrawal Period Hct Results1 (Mean ± 1 SEM) 47 Placebo • Phlebotomy rates N = 582, 1:1 randomization Rusfertide 46 ⎼ >5/yr pre-study vs Dose Finding 1:1 OLE (up to 3

  36. Slide 36: Erythrocytes Decreased; Serum Ferritin Increased Over Time

    Phase 2 REVIVE Study Erythrocytes Decreased Over Time; Serum Ferritin Increased Over Time Erythrocyte (Local) Results (Mean±1 SEM) Serum Ferritin (Central) Data (Mean±1 SEM) SEM, standard error of the mean; yr, year. Pettit K, et al. (S218). HemaSphere 2024;8(Suppl. 1):252. 36

  37. Slide 37: Leukocytes and Platelet Values Stabilized Over Time

    Phase 2 REVIVE Study Leukocytes and Platelet Values Stabilized Over Time Leukocyte (Local) Results (Mean±1 SEM) Platelet (Local) Results (Mean±1 SEM) SEM, standard error of the mean; yr, year. Pettit K, et al. (S218). HemaSphere 2024;8(Suppl. 1):252. 37

  38. Slide 38: Rusfertide Increased Mean Corpuscular Volume (MCV)

    Phase 2 REVIVE Study Rusfertide Increased Mean Corpuscular Volume (MCV) Throughout the Study 94 92 Mean (±SEM) MCV (fL) 90 88 86 84 82 80 78 76 74 0.5 yrs 1 yr 1.5 yrs 2 yrs 2.5 yrs 3 yrs 3.5 yrs n (Placebo) 26 14 7 n (Rusfertide) 58 58 58 57 57 54 40 58 30 24 19 57 57 54 52 55 51 53 48 52 47 52 45

  39. Slide 39: Rusfertide Demonstrated a Favorable Long-Term Safety Profile

    Phase 2 REVIVE Study Rusfertide Demonstrated a Favorable Long-Term Safety Profile1 • No Grade 4 or 5 TEAEs TEAEs (Any Grade) Reported in ≥10 Patients Preferred term Overall, n (%) • Overall, 18 (26%) patients experienced SAEs Patients with at least 1 TEAE 70 (100) • After >150 patient-years of rusfe

  40. Slide 40: Patients in REVIVE Part 3 (OLE) Transitioned to THRIVE

    Patients in REVIVE Part 3 (OLE) Transitioned to THRIVE1,2 • Patients in THRIVE are eligible to continue receiving rusfertide for up to 2 years, or a total of 5.8 years of rusfertide therapy • Of the 58 patients who enrolled in the OLE portion of REVIVE, 46 patients (~80%) transitioned to the phase 2

  41. Slide 41: PTG-300-11 (VERIFY) Study Design and Endpoints

    PTG-300-11 (VERIFY) Study Design and Endpoints Andrew Kuykendall, MD Associate Member Moffitt Cancer Center Tampa, Florida 41

  42. Slide 42: Rusfertide Phase 3 VERIFY Study

    Rusfertide Phase 3 VERIFY Study Topline Results Expected in March 2025 VERIFY (N~250) Rusfertide + ongoing therapy* Durability of Response Primary Endpoint 1:1 randomization R Period Rusfertide + ongoing therapy* (Weeks 20-32) (Weeks 32-52) Placebo + ongoing therapy* Week 0 20 28 32 40 52 156 197 Pa

  43. Slide 43: Key PRO Endpoints and Similarities/Differences Between VERIFY and REVIVE

    PTG-300-11 (VERIFY) Study: Key PV-Focused PRO Endpoints and Key Similarities/Differences Between VERIFY and REVIVE Arturo Molina, MD, MS, FACP Chief Medical Officer Protagonist Therapeutics, Inc. Newark, California

  44. Slide 44: Study Design: Phase 2 REVIVE vs Phase 3 VERIFY Study

    Study Design: Phase 2 REVIVE vs Phase 3 VERIFY Study Primary Efficacy Endpoint, Patient Population, and Inclusion Criteria are Similar in REVIVE and VERIFY Rusfertide + OT Phase 2 REVIVE Study (N=70) Primary Endpoint Rusfertide + OT R Period Rusfertide + ongoing therapy (Weeks 28-40) Placebo + OT Ra

  45. Slide 45: REVIVE Part 1 (Open-Label): PROs assessed using the MPN-SAF TSS 10

    REVIVE Part 1 (Open-Label): PROs assessed using the MPN-SAF TSS 101,2 Rusfertide Improved Symptoms in Patients With Moderate or Severe Symptoms at Baseline • In patients with moderate or severe symptoms at Baseline (≥4 out of 10), rusfertide significantly decreased symptoms in fatigue, early satiety

  46. Slide 46: REVIVE Part 3 (Open Label Extension): PROs assessed using MPN-SAF TSS 10

    REVIVE Part 3 (Open Label Extension): PROs assessed using the MPN-SAF TSS 101 Rusfertide Improved Symptoms in Patients With Moderate or Severe Symptoms at Baseline MPN-SAF, Myeloproliferative Neoplasm Symptom Assessment Form; SD, standard deviation. Data in the figure above are shown for each indivi

  47. Slide 47: VERIFY: Key PRO-Related Secondary Endpoints at Week 32

    VERIFY: Key PRO-Related Secondary Endpoints at Week 32 Includes All Patients* Irrespective of Symptom Status at Baseline Endpoint Description Instrument Symptom(s) Comparison of rusfertide to placebo: • Mean change from baseline at end of Part 1a (Week 32) in the SF-8a  PROMIS Fatigue SF-8a 1,2 Fat

  48. Slide 48: VERIFY: PV-Focused PRO-Related Secondary Endpoints at Week 32

    VERIFY: PV-Focused PRO-Related Secondary Endpoints at Week 32 Focused on Patients With Moderate or Severe Symptoms at Baseline Endpoint Description Instrument Symptom(s) Comparison of rusfertide to placebo: • Mean change from baseline at end of Part 1a (Week 32) in the SF-8a  PROMIS Fatigue SF-8a1,

  49. Slide 49: Rusfertide: Clinical Development in Patients with Polycythemia Vera

    Rusfertide: Clinical Development in Patients with Polycythemia Vera Disc./Pre-Clinical Phase 1 Phase 2 Phase 3 Key Milestones Polycythemia Vera (PV) HEMATOLOGY VERIFY Ph 3, n~250 • Top-line 32-Wk Primary EP results March‘25 RUSFERTIDE REVIVE Ph 2, n=70 • Study completed; OLE ongoing Hepcidin Mimetic

  50. Slide 50: Commercial Overview: Rusfertide

    Commercial Overview: Rusfertide Lopa Desai Commercial Strategy Advisor Protagonist Therapeutics, Inc. Newark, California 50

  51. Slide 51: Polycythemia Vera (PV): Significant Unmet Medical Need

    Polycythemia Vera (PV) Significant Unmet Medical Need Inconsistent Hematocrit (Hct) Control Increased Risk of Thrombotic Events Therapies for Patients • Hct control <45% is critical, as • 34-41% of patients experience • Current standard of care (SOC) uncontrolled Hct is associated with ~4 thrombotic

  52. Slide 52: Patient Journey in PV Identifies Unmet Need in Current Treatment Paradigm

    Patient Journey in PV Identifies Unmet Need in Current Treatment Paradigm Patients Cycle Through Treatment Options with Inconsistent Hct and Tolerability Presentation and Initial Treatment and Cycling Through Ongoing PV Diagnosis Management Treatment Options Management Initial presentation: Immediat

  53. Slide 53: Rusfertide has $1-2 Billion Peak Revenue Potential

    Rusfertide has $1-2 Billion Peak Revenue Potential1 Rapid, Consistent and Sustained Hematocrit Control Treatment Paradigm Patients are often on polytherapy and will cycle through various treatments2 ~155k diagnosed patients in the US with ~41K ~26K ~6K ~3K Phlebotomy And/Or Hydroxyurea And/Or And/Or

  54. Slide 54: Unlocking the Full Potential of Rusfertide for PV Patients

    Unlocking the Full Potential of Rusfertide for PV Patients Advancing Care in the PV Space by Targeting Critical Unmet Needs Approximately 155,000 patients diagnosed with PV with only 78,000 currently on treatment Hematocrit control (<45%) is the primary goal of physicians in treating patients with P

  55. Slide 55: Closing Remarks

    Closing Remarks Dinesh Patel, PhD Director, President, and CEO Protagonist Therapeutics, Inc. Newark, CA 55

  56. Slide 56: Key Near-Term Rusfertide Milestones

    Key Near-Term Rusfertide Milestones Q4 2024 Q1 2025 Q2 2025 Q4 2025  PV Day1  ASH 2024 Rusfertide  Ph3 VERIFY topline2  NDA filing  Rat 2-year  Final study report and FDA  EHA 2025  ASH 2025 carcinogenicity study* submission *No rusfertide-related findings in the draft audited pathology repo

  57. Slide 57: Thank You

    Protagonist Therapeutics Thank You

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