Protagonist Therapeutics, Inc. · NASDAQ:PTGX
Protagonist Therapeutics — Investor Presentation (January 2024)
60 slides from Protagonist Therapeutics's investor presentation, Jan 8, 2024
Slide 1: Company Overview
COMPANY OVERVIEW Dinesh V. Patel, Ph.D. President & CEO January 08, 2024 1
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: Core Competency Remains our Focus: Expertise in Peptide-based Medicines
Core Competency Remains our Focus Expertise in 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 Availa
Slide 4: Product Pipeline: Multiple Assets with Multi-Billion Dollar Market Potential
Disc./Pre - Clinical Phase 1 Phase 2 Phase 3 Key Milestones ICONIC - LEAD Ph3, n~600 PACIFIC Ph2 Elevated Hct (>48%), n=20 REVIVE Ph2, n=70, 40 wk study + 3 yr OLE RUSFERTIDE Hepcidin Mimetic • Enrollment completion 1Q 24 • Completed; OLE ongoing • Completed 1 See clinicaltrials.gov NCT06095115 2 Se
Slide 5: Major Catalysts Ahead
2023 2024 2025 2026 Q4 Q1 Q2 Q3 Q4 ASH JNJ - 2113 Janssen Major Catalysts Ahead A Transformative Path Forward for Protagonist, from Discovery to Development to Commercialization Program Rusfertide in PV JNJ - 2113 Janssen Discovery & Pre - Clinical 5
Slide 6: Rusfertide: Addressing Unmet Needs in Polycythemia Vera
Rusfertide Hepcidin Hormone Mimetic Addressing Unmet Needs in Polycythemia Vera 6
Slide 7: 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 • Elevated hematocrit (Hct) is a hallmark of the disease, indicating overproduction of RBCs 2 Serious, chronic disease associate
Slide 8: Current Treatment Challenges in PV
1. Verstovsek S, et al. Ann Hematol. 2023 Mar;102(3):571 - 581 2. Marchioli R, et al. N Engl J Med 2013; 368:22 - 33 3. Verstovsek S, et al. Leuk Res. 2017;56:52 - 59. doi:10.1016/j.leukres.2017.01.032. 4. McMullin MF, et. al. Br J Haematol. 2019 Jan; 184(2): 176 - 191. 5. Mesa R, et al. BMC Cancer.
Slide 9: Hydroxyurea is the Gatekeeper to Other Agents in PV
Hydroxyurea is the Gatekeeper to Other Agents in PV 9 HU, used alone or in combination with phlebotomy, is the most common 2 nd and 3 rd line PV therapy 1 Many patients require high doses of HU, but still experience inadequate Hct control • 60% of patients receiving HU require ≥ 1,000mg daily 1 • 35
Slide 10: Interferon and Ruxolitinib in PV
Interferon Pegasys ®, Besremi ® Interferons have long been used off - label in PV treatment; Besremi is the first interferon product approved for PV 1 Slow onset of action, with a verage time to response of 1.2 to 1.4 years 2 Failed to show noninferiority to HU at 12 months in the PROUD - PV study 3
Slide 11: Increased Hematocrit is Associated with Increased Morbidity and Mortality
Increased Hematocrit is Associated with Increased Morbidity and Mortality 11 Current Treatment Options are Inadequate Alberto Alvarez - Larran et al. Haematologica 2017; 102:103 - 109 Marchioli, R. et al., N Engl J Med . 2013;368(1):22 - 33. ≥3 PTB/year (N=85) 0 - 2 PTB/year (N=448) Phlebotomy, Ev
Slide 12: Thromboembolic Events are Associated with PV
Thromboembolic Events are Associated with PV 12 • In observational studies, patients with PV had higher rates of TEs compared to matched controls (14.3 vs 4.9/1000 patient years) 1 - 3 • In a retrospective analysis of US electronic health records contained in the Optum ® MarketClarity database, TEs
Slide 13: Burden of Treatment Impacts Treatment Strategy
Burden of Treatment Impacts Treatment Strategy 13 Guidelines Use Risk to Govern Treatment Strategy, but Treatment Burden Has Real - World Significance Risk Stratification Treatment Burden • NCCN guidelines characterize PV patients as low - or high - risk, defined as: – Low - risk: age <60 years with
Slide 14: Defining the Moderate Treatment Burden Population
Defining the “moderate treatment burden " population using current market treatments and trends is the key to understanding rusfertide's market opportunity Phlebotomy Frequency Dosing of Hydroxyurea Thrombotic Events A high frequency of phlebotomies indicates the intervention is not working to maint
Slide 15: Rusfertide for Polycythemia Vera
Rusfertide for Polycythemia Vera 15 Successful Phase 2 Completion and Phase 3 Enrollment Nearing Completion • Phase 2 REVIVE Study (n=70): – Randomized withdrawal data presented at EHA 2023 1 as a late breaker oral ▪ 69% responder rate (vs. 19% placebo; p=0.0003) – Long - term extension data present
Slide 16: Clinical Study of Rusfertide in PV Patients with High Hematocrit
Clinical Study of Rusfertide in PV Patients with High Hematocrit (>48%) 1,2 16 Rapid Hematocrit Control <45% Was Achieved • Open - label, 1 year study in PV patients who are newly diagnosed or for whom current treatment is not sufficient to control hematocrit ( Hct ) • Patients met WHO criteria for
Slide 17: REVIVE Study Design
Dose Finding * Efficacy Evaluation * Randomized Withdrawal Open Label Extension 1 PART 1 (28 wks; Wks 1 - 29) PART 2 (up to 12 wks) PART 3 (52 wks 1 ) STUDY HIGHLIGHTS: • Phlebotomy dependent PV patients diagnosed as per 2016 WHO criteria • ≥3 phlebotomies in 6 months with or without concurrent cyto
Slide 18: Baseline Characteristics
Baseline Characteristics Characteristics (n = 70) AGE Range 27 - 77 years (Median, 58) GENDER Females 21 (30.0%) Males 49 (70.0%) RISK Low 30 (42.9%) High 40 (57.1%) [Age based – 37.1%, Thrombotic events – 20.0%] DURATION SINCE PV DIAGNOSIS 1 yr 14 (20.0%) 1 - 3 yrs 23 (32.9%) 3 - 5 yrs 11 (15.7%) >
Slide 19: REVIVE: Durability of Rusfertide Efficacy
Data cutoff: 17 October 2023 REVIVE: Durability of Rusfertide Efficacy 19 Significant Reduction in Therapeutic Phlebotomy • In patients who continued onto Part 3, 32 (55.2%) and 26 (44.8%) patients were treated with phlebotomy alone or phlebotomy with cytoreductive therapy, respectively Phlebotomy O
Slide 20: Randomized Withdrawal: Primary Endpoint Met
Part 2: Blinded Randomized Withdrawal, Weeks 29 - 41 20 Rusfertide Met the Primary Endpoint of Efficacy (p=0.0003) • 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/in
Slide 21: REVIVE: Freedom from Phlebotomy
Phase 2 REVIVE Study: Part 1 and 2 21 Consistent Effects on Freedom from Phlebotomy 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 Rusfertide Rusfertide Dose Titration Open - Label
Slide 22: REVIVE: Time to Event Analysis
Phase 2 REVIVE Study: Time to Event Analysis 22 Rusfertide Associated W ith D elayed T ime to Loss of Response, Phlebotomy E ligibility, and First Hct ≥45% Protagonist Therapeutics, Inc. Data on File. 2 January 2024. Time to Phlebotomy Eligibility 0 20 40 60 80 100 Time to Loss of Response 0 20 40 6
Slide 23: Durable Control of Hematocrit Through 2.5 Years
Rusfertide Provided Durable Control of Hematocrit Through 2.5 Years 23 REVIVE Part 3: Open - Label Extension (OLE) • Rusfertide treatment resulted in consistent maintenance of hematocrit <45% Adapte d from Ritchie EK, et al. Durability of Hematocrit Control in Polycythemia Vera with the First - in -
Slide 24: REVIVE: Symptom Improvement
Phase 2 REVIVE Study: Symptom Improvement 24 Improvement in Ferritin Levels and Symptoms Individual symptoms assessed using MPN - SAF; p - values are based on paired comparisons Baseline (n=25) Week 29 (n=20) 2 4 6 8 10 4.2 6.0 Fatigue Weeks S y m p t o m S c o r e p=0.0074 Baseline (n=18) Week 29 (
Slide 25: REVIVE: Safety and Exposure
Phase 2 REVIVE Study: Safety and Exposure 25 Rusfertide Was Generally Well Tolerated • 70 subjects were enrolled in the rusfertide REVIVE study • 57 subjects (81.4%) have exposure ≥ 1 yr • 51 subjects (72.9%) have exposure ≥ 1.5 yrs • 37 subjects (52.9%) have exposure ≥ 2 yrs • 11 subjects (15.7%) h
Slide 26: REVIVE: Serious Adverse Events
REVIVE: Serious Adverse Events 26 • Overall, 14 patients (20.0%) experienced an SAE* – There were 3 cases of basal cell carcinoma – There was 1 case each of atrial fibrillation, myocardial infarction, anogenital dysplasia, constipation, non - cardiac chest pain, gastroenteritis, sepsis, lung adenoca
Slide 27: Prevalence of Second Cancers in PV
Prevalence of Second Cancers in PV 27 Second Cancers • One large population - based study found that patients with MPNs had a 60% higher risk of developing second non - hematologic cancers compared to matched controls 1 ‒ Skin cancers were among the most prevalent second cancers (2.8 - fold increase
Slide 28: 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 in December 2023; no new safety signals observed 1 • ~250 patient, randomized, placebo - controlled Ph3 V
Slide 29: Phase 3 VERIFY Study Design
Phase 3 Study VERIFY (NCT05210790): Rusfertide vs Placebo in Patients With PV 29 Pathway to Potential Registration in the USA and Europe 2 Year Long - Term Safety Follow - Up (Weeks 52 - 156) Durability of Response (Weeks 32 - 52) Age ≥ 1 8 years Meet revised 2016 WHO criteria for diagnosis of PV ≥3
Slide 30: Potential Commercial Positioning for Rusfertide
Potential Commercial Positioning for Rusfertide Potential Therapy of Choice for Patients with Moderate Treatment Burden 30 Prevalent Patients in US 1 : ~160,000 Diagnosed & Treated Patients 2 : ~100,000 ~30% ~60% ~60,000 patients ~10% Low Moderate Treatment Burden High Komodo claims data 2016 - 2022
Slide 31: Clinical Study of Rusfertide in Patients with Hemochromatosis
Clinical Study of Rusfertide in Patients with Hemochromatosis 31 Control Serum Iron and Reduce Phlebotomies • Open - label, 24 - week proof - of - concept study in patients with hemochromatosis • Eligibility - Adults with HFE - related hemochromatosis. - History of ≥3 phlebotomies in 12 months or ≥4
Slide 32: JNJ-2113: Oral IL-23 Receptor Antagonist Peptide
JNJ - 2113: Oral IL - 23 Receptor Antagonist Peptide Targeted Investigational Therapy for Psoriasis & Other IL - 23 Mediated Diseases
Slide 33: Protagonist-Janssen Oral IL-23R Antagonist Collaboration
Protagonist - Janssen Oral, IL - 23R Antagonist Collaboration 33 JNJ - 2113 highlighted as f irst - and best - in class targeted oral IL - 23 peptide antagonist 2 • "Unprecedented potential" from JNJ - 2113 across multiple indications: IBD, plaque psoriasis, psoriatic arthritis, IBD • PTGX positione
Slide 34: JNJ-2113 Market Potential
JNJ - 2113 Market Potential 1 • 50 - 70% of patients (~5 million in G8) living with psoriatic and IBD conditions and are eligible for advanced therapies, and yet aren't receiving them 34 Big Opportunity for a safe and effective oral, once daily medication 1. JNJ Innovative Medicines Enterprise Busin
Slide 35: JNJ-2113: Preclinical, Phase 1 and Phase 2b Data
JNJ - 2113: Oral, IL - 23R Peptide Antagonist 35 Preclinical, Phase 1 and Phase 2b Data Supportive of a Robust Clinical Development Program 1 1. ISID – Fourie A, et al. First - in - Class Oral Peptide Systemically Targeting the IL - 23 Pathway. Abstract presented at the Inter national Societies for
Slide 36: JNJ-2113 FRONTIER Phase 2b Study Design
JNJ - 2113 FRONTIER 1 Phase 2b Plaque Psoriasis (PsO) Study 36 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) 25 mg QD & Placebo
Slide 37: 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 38: JNJ-2113 Phase 2b FRONTIER Data
JNJ - 2113 Phase 2B Frontier 1 Data 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 dai
Slide 39: Cross-Study Comparison to Phase 2 Benchmarks
79% 60% 41% 41% 11% NR 69% 44% 9% 67% 46% 33% 67% 44% 16% 81% 57% 29% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% % response rate JNJ-2113 Otezla Sotyktu TAK-279 Stelara Tremfya Cross - Study Comparison of JNJ - 2113 to Clinically Relevant Phase 2 Benchmarks 1 1. Cross trial (not head - to - head) compar
Slide 40: 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 40 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).
Slide 41: Treatment-Emergent Adverse Events
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 42: 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 43: Conclusions from Phase 2b Psoriasis Study and Next Steps
JNJ - 2113 (formerly PN - 235) 43 Conclusions from Phase 2b Psoriasis Study and Next Steps • F urther development in psoriasis and other IL - 23 mediated disease indications is warranted • Oral IL - 23R antagonist peptide • First - in - class • Only - in - class • Efficacious, well - tolerated • Wel
Slide 44: JNJ-2113: Multiple Clinical Studies
Study Phase 1 Phase 2 Phase 3 Key Milestones Ph2b in Psoriasis, n~255 JNJ - 2113 Multiple Clinical Studies with Multiple Shots on Goal • NHVs in Australia; completed • Adult Japanese/Chinese participants; completed • Healthy adult Chinese participants; completed • Completed • Delayed release formula
Slide 45: Royalty Milestones Status and Outlook
Royalty Milestones Status and Outlook 2024 and Beyond $172.5M* $795M amount of total future development and sales milestones for which Protagonist remains eligible in upfront and development milestones have been achieved 6% to 10% upward tiering 10% at ≥ $4B net sales Upcoming Potential Milestones 1
Slide 46: Discovery Pipeline and Financial Outlook
Discovery Pipeline Financial Outlook 2024 is a year of pipeline execution and strategic evolution for Protagonist
Slide 47: Discovery Pipeline: Addressing Major Unmet Medical Needs
Discovery Pipeline 47 Leveraging Our Successes to Address Major Unmet Medical Needs and Create Value 1H 2024 1H 2024 Lead Optimization Dev Candidate Nomination Hematology Myeloproliferative Neoplasms I & I Inflammatory & Immunomodulatory Diseases • Leverage end - to - end expertise in MPNs • Build u
Slide 48: Oral IL-17 Peptide Antagonists
Oral IL - 17 Peptide Antagonists 48 • IL - 17 inhibitors expected to lead the I&I space – Global sales expected to increase significantly from ~$29B (2021) to >$50B (2031) for IL - 17 mediated indications 1 – IL - 23 and IL - 17 inhibitors expected to have significant PsO (~80%) and PsA (~60%) marke
Slide 49: Financial Highlights
Financial Highlights 49 * Includes $60M in milestones achieved in Q4 2023 Financial Resources Forecast Extends Through Q1 2026 CASH, CASH EQUIVALENTS & MARKETABLE SECURITIES provide forecast cash runway through Q1 2026* SHARES OUTSTANDING as of September 30, 2023 Q1 2026 ~57.6M CASH, CASH EQUIVALENT
Slide 50: Thank you
Protagonist Therapeutics Thank you
Slide 51: American Society of Hematology Annual Meeting Accepted Abstracts
65 th American Society of Hematology Annual Meeting & Exposition Accepted Abstracts 51
Slide 52: 65th ASH Annual Meeting Company-Sponsored Abstracts
65th ASH Annual Meeting and Exposition (2023) 52 Company - Sponsored Abstracts Day Time (PST) Type Location Presentation/Abstract Title Abstract Number Presenting Author Abstract URL Oral Presentations Sat 9 Dec 10:30 AM Oral Marriott Marquis San Diego Marina, Pacific Ballroom Salons 18 - 19 Real -
Slide 53: Pre-Clinical PoC 1: Rat TNBS-Induced Colitis Model
Pre - Clinical PoC 1: Rat TNBS - Induced Colitis Model 53 Orally Dosed JNJ - 2113 Attenuates Weight Loss and Colon Inflammation • 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
Slide 54: Pre-Clinical PoC 2: Rat IL-23 Induced Skin Inflammation Model
Pre - Clinical PoC 2: Rat IL - 23 Induced Skin Inflammation Model 54 Orally Dosed JNJ - 2113 Achieves Inhibition 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 inhibitio
Slide 55: Phase 1 Study of JNJ-2113 in Healthy Volunteers
Phase 1 Study of JNJ - 2113 in Healthy Volunteers 55 Safety, Pharmacokinetics, Systemic Pharmacodynamics • Demonstrated PoC for systemic PD activity of orally dosed JNJ - 2113 in humans • Single and multiple oral doses were safe and generally well tolerated with no safety signal of concern Fourie A,
Slide 56: ICONIC-LEAD: JNJ-2113 Phase 3 Study
ICONIC - LEAD: JNJ - 2113 Phase 3 Study in Moderate to Severe Plaque Psoriasis 56 n=600 (2:1 randomization) Eligibility: Mod/Severe PsO • IGA > 3 • PASI > 12 • BSA > 10% • Age: > 12 Primary endpoint: • IGA 0/1 Week 16 • PASI 90 Week 16 Study Start Date: 10/12/23 Estimated Primary Completion:11/19/24
Slide 57: ICONIC-TOTAL: JNJ-2113 Phase 3 Study in Special Areas
ICONIC - TOTAL: JNJ - 2113 Phase 3 Study in Plaque Psoriasis Involving Special Areas 57 n=300 (2:1 randomization) Eligibility: Special Areas and Low BSA Mod - Severe • IGA > 2 + BSA > 1% + mod/severe special area (ss - IGA > 3 or sPGA of genitalia > 3 or hf - IGA > 3) OR • IGA > 3, BSA 5 - 10% • Fai
Slide 58: ICONIC-Advance 1: Head-to-Head Versus Deucravacitinib
58 2:1:2 randomization 2113/placebo/deucra, n=750* Eligibility: Mod/Severe PsO • IGA > 3 • PASI > 12 • BSA > 10% • Age: > 18 Primary endpoint: • IGA 0/1 Week 16 • PASI 90 Week 16 Estimated Study Start Date: 2/9/24 Estimated Primary Completion: 3/13/25 Week 0 Randomize Week 16 Primary Endpoint Placeb
Slide 59: ICONIC-Advance 2: Head-to-Head Versus Deucravacitinib
59 4:1:4 randomization 2113/placebo/deucra, n=675* Eligibility: Mod/Severe PsO • IGA > 3 • PASI > 12 • BSA > 10% • Age: > 18 Primary endpoint: • IGA 0/1 Week 16 • PASI 90 Week 16 Estimated Study Start Date: N/A Estimated Primary Completion: N/A Week 0 Randomize Week 16 Primary Endpoint Placebo JNJ -
Slide 60: ANTHEM-UC: JNJ-2113 Phase 2b Study in Ulcerative Colitis
ANTHEM - UC: JNJ - 2113 Phase 2b Study in Moderate to Severe Ulcerative Colitis 60 Adult Patients with UC n=~240 Eligibility: • 18 years of age or older • Moderately to severely active UC as per the modified Mayo score • Demonstrated inadequate response to or intolerance of conventional therapy and/
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