Protagonist Therapeutics, Inc. · NASDAQ:PTGX
Protagonist Therapeutics — Investor Presentation (July 2023)
58 slides from Protagonist Therapeutics's investor presentation, Jul 5, 2023
Slide 1: Company Overview
1 COMPANY OVERVIEW Dinesh V. Patel, Ph.D. President & CEO July 04, 2023
Slide 2: Forward-looking Statements
Forward - looking Statements 2 This presentation and the accompanying oral presentation contain forward - looking statements made pursuant to the safe harbor pro visions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in thi
Slide 3: Protagonist Therapeutics: Peptide-based Medicines
Protagonist Therapeutics 3 Peptide - based Medicines Potency Peptide Chemistry SAR, Leads Phage Libraries Hits Computational Vectrix, Clusters Vectrix ® Clusters 1 2 3 POTENCY Oral Stability Peptidomimetics GI Assays GI-Restricted Targeted GI absorption & delivery Systemic Availability Formulation S
Slide 4: Ongoing Ph3 Study of Rusfertide in PV | Collaboration with Janssen
Ongoing Ph3 Study of Rusfertide in PV | Collaboration with Janssen Toward Oral IL - 23R Antagonist 4 • JNJ - 2113*(formerly PN - 235) – Collaboration with Janssen – Oral IL - 23R antagonist – Multiple clinical studies ▪ FRONTIER 1: Ph2b study in psoriasis** ▪ FRONTIER 2: Extension of FRONTIER 1 ▪ SU
Slide 5: Ongoing Projects and Future Plans
Discovery, Pre - Clinical & Clinical Development 5 • Primary focus on completing Phase 3 VERIFY study of Rusfertide in polycythemia vera • Separate 2 - year extension (PTG - 300 - 21) study will open this year for patients who have completed participation in the REVIVE study – Total duration of trea
Slide 6: Product Portfolio Addressing Unmet Needs
UC Ph2b trial (planned) INFLAMMATORY & IMMUNOMODULATORY DISEASES Oral IL - 23R Antagonist (Partnered) JNJ - 2113 (PN - 235) Hematology Ph3 trial (planned) Programs Discovery/ Pre - Clinical Phase 1 Phase 2 Phase 3 Key Milestones HEMATOLOGY & BLOOD DISORDERS Hepcidin Mimetic Rusfertide (PTG - 300) Ph
Slide 7: Rusfertide (PTG-300): Hepcidin Mimetic Addressing Unmet Needs in Polycythemia Vera
Rusfertide (PTG - 300): Hepcidin Mimetic Addressing Unmet Needs in Polycythemia Vera
Slide 8: Rusfertide Building a Heme Franchise
Rusfertide 8 Building a Heme Franchise • Efficacy • Durability of Response • QoL – Symptom Improvement • Safety • New studies in PV Polycythemia Vera • Positive clinical PoC Hereditary Hemochromatosis • Sickle cell disease • Porphyria • Erythrocytosis Potential Indications Under Review
Slide 9: Polycythemia Vera Disease Background
Myeloproliferative neoplasm characterized by excessive production of red blood cells ( RBCs) 1 Treatment goal is to control HCT <45% to minimize TEs, CV events, and death 3 9 • Elevated hematocrit (HCT) is a hallmark of the disease, indicating overproduction of RBCs 2 Serious, chronic disease associ
Slide 10: A Blood Disorder with Significant Unmet Needs with Current SOC
Polycythemia Vera • Burdensome symptoms including fatigue and concentration problems 2 – 84% of patients report fatigue, and 23% report spending full days in bed because of symptoms 3 • Impacts patient reported activities of daily living and reduce productivity 2 A Blood Disorder with Significant Un
Slide 11: Current Treatment Options for PV and Potential Limitations
Current Treatment Options for PV and Potential Limitations 11 Cytoreductive Therapies May Lead to Intolerance and/or Inadequate Hematocrit Control Hydroxyurea Hydrea ® Typically used as a first - line treatment in high - risk patients Patients still experience periods where HCT > 45% , 1 potentially
Slide 12: Only 22% of PV Patients Have Consistently Controlled Hematocrit
Only 22% of PV Patients Have Consistently Controlled Hematocrit 12 HCT is Not Managed to Guidelines, Regardless of Patients’ Risk Status Some or All Tests >45% All Tests <45% 22% 78% 85% 37% 53% 10% All HCT tests >50% Some HCT tests >50% All HCT tests <50% All HCT tests <45% Of the 78% of uncontroll
Slide 13: Increased Hematocrit Is Associated with Increased Morbidity and Mortality
Increased Hematocrit Is Associated with Increased Morbidity and Mortality 13 Alberto Alvarez - Larran et al. Haematologica 2017; 102:103 - 109 Marchioli , R. et al., N Engl J Med. 2013 ≥3 PTB/year (N=85) 0 - 2 PTB/year (N=448) Phlebotomy, Even with Concomitant Cytoreductive Therapy, Is Inadequate in
Slide 14: Rusfertide: Mechanistic Rationale for Potential Treatment of PV
FERROPORTIN Normalized Hematocrit 45% SERUM IRON IRON DELIVERY MOA of rusfertide RBC PRODUCTION RUSFERTIDE Rusfertide: Mechanistic Rationale for Potential Treatment of PV 14 FERROPORTIN transports iron HEPCIDIN Inhibits ferroportin serum iron Transferrin delivers iron EXCESSIVE RBC PRODUCTION 45% El
Slide 15: Rusfertide for Polycythemia Vera: Three Clinical Studies Ongoing
Rusfertide for Polycythemia Vera 15 Three Clinical Studies Ongoing • Ph3 VERIFY Study (n=250): − Study execution continues with enrollment completion expected in 1Q 2024 − Agreed upon Phase 3 VERIFY protocol with the FDA and CHMP (EU) • Phase 2 PACIFIC Study: − High hematocrit (HCT >48%) 16 - week s
Slide 16: PACIFIC Study in PV Patients with High HCT (>48%)
PACIFIC Study in PV Patients with High HCT (>48%) HCT (n=1 7 ) Data cutoff: April 1 7 , 202 3 , *Subjects with complete restart data
Slide 17: Phase 2 Study of Rusfertide in PV Patients (REVIVE)
PART 1 (28 wks ; Wks 1 - 29) PART 2 (up to 12 wks ) PART 3 (52 wks 1 ) Dose Finding * Efficacy Evaluation * Randomized Withdrawal Open Label Extension 1 Phase 2 Study of Rusfertide in PV Patients (REVIVE) 17 GOAL: Maintain Hematocrit <45% STUDY HIGHLIGHTS: • Phlebotomy dependent PV patients diagnose
Slide 18: Baseline Characteristics of Study Participants in REVIVE Study
Baseline Characteristics of Study Participants in REVIVE Study Characteristics (n = 70) AGE Range 27 - 77 years (Mean = 57.3 yrs ) GENDER Females 21 (30.0%) Males 49 (70.0%) RISK Low 29 (41.4%) High 41 (58.6%) [Age based – 37.1%, Thrombotic events – 21.4%] DURATION SINCE PV DIAGNOSIS <1 yr 14 (20.0%
Slide 19: Meaningful Reduction in Phlebotomy Frequency During Dose Finding (Part 1)
Meaningful Reduction in Phlebotomy Frequency During Dose Finding (Part 1) Phlebotomy + Cytoreductive (n= 33) Data cutoff: Feb 15, 2023 19 Phlebotomy Only (n=37)
Slide 20: Unblinding of the Randomized Withdrawal, Part 2 of the REVIVE Study
PART 1 (28 wks ; Wks 1 - 29) PART 2 (up to 12 wks ) PART 3 (52 wks 1 ) Dose Finding * Efficacy Evaluation * Randomized Withdrawal Open Label Extension 1 Unblinding of the Randomized Withdrawal, Part 2 of the REVIVE Study 20 Highly Statistically Significant Results Dose ± Titration Fixed Active/Place
Slide 21: REVIVE Study: Part 2, Blinded Randomized Withdrawal
REVIVE Study: Part 2, Blinded Randomized Withdrawal, Weeks 29 - 41 21 • 69.2% subjects (18 out of 26) are responders. 8 non - responders as per protocol definition – 3 fulfilled the phlebotomy eligibility criteria – 5 discontinued treatment per patient/investigator discretion • All 8 non - responder
Slide 22: Significant Impact of Rusfertide Withdrawal During Blinded Phase (Part 2)
Significant Impact of Rusfertide Withdrawal During Blinded Phase (Part 2) Placebo Data cutoff: Feb 15, 2023 22 Rusfertide Part 1 Part 2 Part 1 Part 2
Slide 23: REVIVE Study: Efficacy
REVIVE Study: Efficacy 23 Consistent Effects on Being Phlebotomy Free in Open - Label (87%) vs. Double - blind (92%) Parts of Study Wk 1-17 (N=65) Wk 17-29 (N=63) Wk 29-41 (N=26) 0 20 40 60 80 100 92.3% 87.3% 76.9% P e r c e n t o f S u b j e c t s n=24 n=50 n=55 Part 1 Part 2 Phlebotomy - Free on R
Slide 24: REVIVE Study: Consistent Efficacy
REVIVE Study: Consistent Efficacy 24 Rusfertide Significantly Delays Time to Event on Multiple Outcomes Compared to Placebo 28 30 32 34 36 38 40 42 0 20 40 60 80 100 Responder Weeks P e r c e n t o f S u b j e c t s P <0.0001 P <0.0001 28 30 32 34 36 38 40 42 0 20 40 60 80 100 Absence of PHL Eligibi
Slide 25: REVIVE Study: Ferritin Levels & Improvement in PV Symptoms in Part 1
REVIVE Study: Ferritin Levels & Improvement in PV Symptoms in Part 1 25 Improvement in Ferritin and Symptoms - Moderate or Severe Symptoms at Baseline Individual symptoms assessed using MPN - SAF p - values are based on paired comparisons Symptom Improvement in Part 1 (28 - Weeks) Baseline (n=25) We
Slide 26: Durability of Hematocrit Control with Rusfertide in REVIVE Study
Durability of Hematocrit Control with Rusfertide in REVIVE Study 26
Slide 27: REVIVE Study – Safety and Exposure
REVIVE Study – Safety and Exposure 27 • 70 subjects were enrolled in the rusfertide REVIVE study – 52 subjects (74.3%) have exposure ≥ 1 yr – 32 subjects (45.7%) have exposure ≥ 1.5 yrs – 10 subjects (14.3%) have exposure ≥ 2 yrs – 3 subjects (4.3%) have exposure ≥ 2.5 yrs • Rusfertide was generally
Slide 28: REVIVE Study: Overall Safety
REVIVE Study: Overall Safety 28 No New Safety Signals Data as of 15 February 2023 • 18.6% subjects reported an SAE • A total of 7 subjects diagnosed with malignancy after starting the study – All 7 subjects had risk factors before exposure to rusfertide including pre - malignant lesions, history of
Slide 29: Rusfertide Summary
• Rapid HCT control (<45%) without phlebotomy in high HCT (>48%) PACIFIC study • Rusfertide treatment with or without cytoreductives appears to be well tolerated – Safety update presented at ASH, December 2022; no new safety signals observed 1 • ~250 patient, randomized, placebo - controlled Ph3 VER
Slide 30: Randomized, Double-blind, Placebo-Controlled Phase 3 VERIFY PV Study
Part 1a Double Blind ( Weeks 0 - 32) Dose Titration Primary Efficacy (Weeks 0 - 20) (Weeks 20 - 32) Part 1b Durability of Response (Weeks 32 - 52) Screening (Up to 4 Weeks) Randomized, Double - blind, Placebo - Controlled Phase 3 VERIFY PV Study 30 Ongoing Study of N~250 Subjects The Phase 3 study d
Slide 31: PV Market Overview
PV Market Overview ~100,000 Diagnosed & Treated Patients in the U.S. 2 Rusfertide has the potential to create a new standard of care in PV x Broad spectrum of patients x Competition with distinct limitations x High unmet needs with uncontrolled patients ~ 160,000 Prevalent Patients in the U.S. 1 1.
Slide 32: Identifying PV Patients with Moderate Treatment Burden
Identifying PV Patients with Moderate Treatment Burden Defining the “moderate burden“ population using current market treatments and trends is the key to understanding rusfertide's market opportunity Phlebotomy Frequency An increase in frequency of phlebotomies indicates the intervention is not work
Slide 33: Potential Commercial Positioning for Rusfertide
Potential Commercial Positioning for Rusfertide Therapy of Choice for Patients Experiencing Moderate Treatment Burden to Achieve HCT Control Low burden Infrequent Phlebotomy (<4/year) High burden Other Agents Moderate burden Frequent Phlebotomy and/or HU Illustrative rusfertide target. Percentages d
Slide 34: JNJ-2113 (formerly PN-235): Oral IL-23 Receptor Antagonist for Psoriasis
JNJ - 2113 (formerly PN - 235): IL - 23 Receptor Antagonist Oral Targeted Investigational Therapy for Psoriasis and Other IL - 23 Mediated Diseases 34
Slide 35: Protagonist-Janssen Oral IL-23R Antagonist Collaboration
Protagonist - Janssen Oral, IL - 23R Antagonist Collaboration 35 1 Stelara® generated $9.7B in sales, and Tremfya® generated $2.7B in sales in 2022, per Johnson & Johnson 2022 Annual Report. Ste lara® and Tremfaya ® not part of Protagonist - Janssen collaboration. Collaboration overview – Initiated
Slide 36: IL-23R Antagonist Market Overview
IL - 23R Antagonist Market Overview 36 Multi - billion Market Opportunity for an Oral Agent Significant market potential for IL - 23R antagonist – Relevant indications include psoriasis, psoriatic arthritis, IBD (ulcerative colitis, Crohn’s disease) – Psoriasis prevalence = 125M WW patients 1 (8M US
Slide 37: Psoriasis Treatment Overview
Psoriasis Treatment Overview JNJ - 2113 is a Potential First, Best, Only - in - Class Drug Candidate • Biological target: IL - 23 receptor • Drug delivery: Oral • Chemical modality: Peptide Injectable IL - 23 antagonists demonstrate robust efficacy and safety in psoriasis JNJ - 2113 (formerly PN - 2
Slide 38: JNJ-2113 Multiple Clinical Studies in Progress & Planned
JNJ - 2113 (PN - 235) 38 Multiple Clinical Studies in Progress & Planned • Planned – Phase 3 study for moderate - to - severe plaque psoriasis – Phase 2b study for ulcerative colitis • FRONTIER 1 – 255 patient Phase 2b placebo - controlled study in moderate - to - severe plaque psoriasis – Oral tabl
Slide 39: JNJ-2113 Characteristics
JNJ - 2113 Characteristics • Highly potent (single digit picomolar) oral IL - 23R antagonist: – >1000 - fold more potent vs first - generation candidate (PBMC, phospho - STAT3 assay) – Similar or better target affinity vs. IL - 23 mAbs • High oral stability: Ex - vivo stability: >24hr half - life in
Slide 40: In Vitro Pharmacology
In Vitro Pharmacology • JNJ - 2113 is a competitive peptide antagonist that binds with high affinity to IL - 23R, and selectively inhibits IL - 23 proximal signaling and downstream cytokine production with high potency 40 • Binds with high affinity (K D 2 pM ) to human IL - 23R (SPR) • Potently inhi
Slide 41: Orally Dosed JNJ-2113 Attenuates Weight Loss and Colon Inflammation in Rat Colitis Model
Orally Dosed JNJ - 2113 Attenuates Weight Loss and Colon Inflammation in the Rat TNBS - induced Colitis Model • Statistically significant effects seen beginning at doses of 0.1 to 0.3 mg/kg/day • Although exposure in plasma and skin was much lower than GI tissues, exquisite potency of JNJ - 2113 ind
Slide 42: Orally Dosed JNJ-2113 Shows Systemic Pharmacodynamic Activity in Rat Blood
Orally Dosed JNJ - 2113 Shows Systemic Pharmacodynamic Activity in Rat Blood • Dose - dependent inhibition of ex vivo IL - 23 - stimulated IL - 17A production in rat blood 42 Fourie A, et al. ISID Meeting; May 10 - 13, 2023; Tokyo, Japan. ns=not significant, *p <0.05, ****p <0.0001. Graph represents
Slide 43: Oral JNJ-2113 Achieves Inhibition of IL-23-induced Rat Skin Inflammation
Oral JNJ - 2113 Achieves Inhibition of IL - 23 - induced Rat Skin Inflammation Equivalent to Anti - IL - 23 Antibody • Doses ≥ 1 mg/kg BID reduced inflammation and cytokine induction (IL - 17A, IL - 17F and IL - 22) • Doses ≥ 10 mg/kg BID showed equivalent inhibition to an anti - IL - 23 antibody 43
Slide 44: JNJ-2113 Phase 1 Study: Safety, Pharmacokinetics, Systemic Pharmacodynamics
JNJ - 2113 Phase 1 Study: Safety, Pharmacokinetics, Systemic Pharmacodynamics • Demonstrated PoC for systemic PD activity of orally dosed JNJ - 2113 in humans • Phase 2 dose ranging study in patients with moderate - to - severe PsO completed in February 2023 44 Fourie A, et al. ISID Meeting; May 10
Slide 45: JNJ-2113 FRONTIER Phase 2b Plaque Psoriasis Study
JNJ - 2113 FRONTIER 1 Phase 2b Plaque Psoriasis ( PsO ) Study 45 Adult Patients with PP N=255 Eligibility: • Moderate – Severe PP Inclusion: • BSA > 10% • PASI > 12 Primary endpoint: • PASI > 75 at Week 16 Screening Treatment Safety Follow - up (4 Weeks) (Up to 4 Weeks)* (Weeks 0 - 16) Dose 1 QD & P
Slide 46: Demographics and Disease Characteristics at Baseline
Demographics and Disease Characteristics at Baseline BID=Twice daily; BMI=Body mass index; IGA=Investigator’s Global Assessment; PASI=Psoriasis Area and Severity Index; PsO=Psoriasis; PUVA=Psoralen plus ultraviolet A; QD=Daily; UVB=Ultraviolet B. Data shown are mean (SD), unless otherwise indicated.
Slide 47: Proportion of Patients Achieving PASI 75 at Week 16
Non - responder imputation * nominal p <0.001 vs placebo; ** nominal p<0.01 vs placebo. p - values are based on Cochran - Mantel - Haenszel (CMH) chi - square test stratified by baseline weight category (≤90 kg, >90 kg). Patients who discontinued study agent due to lack of efficacy, worsening of PsO
Slide 48: JNJ-2113 Phase 2B Frontier Data
JNJ - 2113 Phase 2B Frontier 1 Data 48 37.2% 51.2% 58.1% 65.1% 78.6% 9.3% 25.6% 26.8% 51.2% 46.5% 59.5% 2.3% 11.6% 9.8% 25.6% 23.3% 40.5% 0.0% 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% 80.0% 90.0% 25 mg daily (n= 43) 25 mg twice daily (n= 41) 50 mg daily (n=43) 100 mg daily (n=43) 100 mg twice
Slide 49: Cross-Study Comparison of JNJ-2113 to Clinically Relevant Phase 2 Benchmarks
Cross - Study Comparison of JNJ - 2113 to Clinically Relevant Phase 2 Benchmarks 1 49 1. Cross trial (not head - to - head) comparisons 2. J NJ2113 100 mg bid dose. Wk 16 endpoint (Placebo: PASI 75: 9.3%, PASI 90: 2.3%, PASI 100: 0%) 3. Otezla 30 mg qd approved dose. Week 16 primary endpoint. Papp K
Slide 50: Proportion of Patients Achieving IGA 0/1 Through Week 16
Proportion of Patients Achieving IGA 0/1 and IGA 0 (95% CI) Through Week 16 Non - responder imputation * nominal p <0.001 vs placebo; ** nominal p<0.01 vs placebo. p - values are based on Cochran - Mantel - Haenszel (CMH) chi - square test stratified by baseline weight category (≤90 kg, >90 kg). Pat
Slide 51: Patients With ≥1 TEAE by System Organ Class and Preferred Term
Number of Patients With ≥1 TEAE With Frequency of ≥5% of Preferred Terms in Any Treatment Group Through End of Study by System Organ Class and Preferred Term AE=Adverse event; BID=Twice daily; QD=Daily; TEAE=Treatment - Emergent Adverse Events. * Includes all JNJ - 2113 treatment columns. Patients a
Slide 52: FRONTIER 1 Safety Summary
There were no deaths, MACE, or malignancies during the study. A low number of laboratory abnormalities occurred during the study and were comparable between placebo and JNJ - 77242113 groups. There was no evidence of a dose - dependent increase in the occurrence of abnormalities. There were three se
Slide 53: Conclusions from FRONTIER 1 Phase 2b PsO Study and Next Steps
JNJ - 2113 53 The FRONTIER 1 results support further development of JNJ - 77242113 in phase 3 studies in psoriasis as well as other IL - 23 mediated disease indications Conclusions from FRONTIER 1 Phase 2b PsO Study and Next Steps A dose response in PASI scores (75, 90, 100) was demonstrated JNJ - 7
Slide 54: Janssen SUMMIT Phase 2a Plaque Psoriasis Study Design
Janssen SUMMIT Phase 2a Plaque Psoriasis ( PsO ) Study Design Delayed Release QD Tablets Adult Patients with PP N =9 0 Eligibility: • Moderate – Severe PP Inclusion: • BSA > 10% • PASI > 12 Primary endpoint: • PASI > 75 at Week 16 Safety Follow - up (4 Weeks) Screening (Up to 4 Weeks)* Treatment (We
Slide 55: Janssen Milestones Status and Outlook 2023 and Beyond
Royalty Janssen Milestones Status and Outlook 55 2023 and Beyond $112.5m $855m Total future development and sales milestones for which Protagonist remains eligible Upfront and development milestones that have been achieved 6% to 10% • Upward tiering • 10% at >$4B net sales Upcoming Potential Milesto
Slide 56: Financials
& Protagonist Therapeutics Financials
Slide 57: Financial Highlights
Financial Highlights Financial Resources Forecast Extends Through Full Year 2025 CASH & SECURITIES *as of March 31, 2023 **follow - on offering April 2023 CASH & SECURITIES provide financial resources forecast through full year 2025 1 SHARES OUTSTANDING as of March 31, 2023 2025 ~57.2M $230.8M* + $1
Slide 58: Thank you
& Protagonist Therapeutics Thank you
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