Protagonist Therapeutics, Inc. · NASDAQ:PTGX
Protagonist Therapeutics — Investor Presentation (April 2022)
48 slides from Protagonist Therapeutics's investor presentation, Apr 13, 2022
Slide 1: Company Overview
1 COMPANY OVERVIEW Dinesh V. Patel, PhD | President & CEO April 2022
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: Discovery and Development of Novel Peptide Therapeutics
Protagonist Therapeutics Discovery and Development of Novel Peptide Therapeutics in Rare and Common Diseases 3 • Proprietary Peptide Technology Platform for de novo discovery and optimization of first - in - class and best - in - class medicines – Applied to develop agonists and antagonists of diffi
Slide 4: Proprietary peptide technology platform
Protagonist Therapeutics 4 Discovering novel peptide therapeutics through a proprietary technology platform and developing them to address unmet medical needs in both rare and common diseases Peptide - based Medicines Rusfertide PN - 943 PN - 235 Peptide Chemistry SAR, Leads Phage Libraries Hits Com
Slide 5: Product Portfolio
PROGRAMS CANDIDATE STUDY PHASE 1 PHASE 2 Key Milestones HEMATOLOGY & BLOOD DISORDERS Hepcidin Mimetic rusfertide (PTG - 300) s.c. VERIFY 300 - 11 PV Ph3 • Sites activated, screening underway REVIVE 300 - 04 • Enrollment complete • Updates at 2022 medical conferences PACIFIC 300 - 08 • All patients r
Slide 6: Rusfertide (PTG-300): Hepcidin Mimetic
5 Rusfertide (PTG - 300): Hepcidin Mimetic To Potentially Address Unmet Needs in Both Rare & Common Diseases
Slide 7: Polycythemia Vera Disease Background
Polycythemia Vera 7 Disease Background Myeloproliferative neoplasm characterized by excessive production of red blood cells (RBCs) • Characterized by Janus Kinase 2 (JAK2) mutation Treatment goal is to control hematocrit level <45% • Elevated hematocrit is a hallmark of the disease • Maintaining hem
Slide 8: Rusfertide for Polycythemia Vera: Current Status and Recent Progress
Rusfertide for Polycythemia Vera 8 Overview of Current Status and Recent Progress • Orphan Drug designation, Fast Track status, and Breakthrough Therapy designation • Phase 2 REVIVE Study: − Clinical update presented at ASH 2021 − Enrollment complete; post - hold re - enrollment rate of 87% • Phase
Slide 9: Polycythemia Vera Current Treatment Options
Polycythemia Vera 9 Current Treatment Options 1. MPN Landmark Survey 2017, Trinity Primary Research 2019 • Treatment goal is to maintain HCT ≤ 45% • HCT control may be erratic with up and down excursions from 45% • Can lead to iron deficiency • Recommended when HCT cannot be controlled, or in high -
Slide 10: Understanding PV Patient Journey
Understanding PV Patient Journey 10 Evaluating the Unmet Need of PV Patients in US 1 Symphony Patient Journey Data Large, representative, and longitudinal source of healthcare claims data that captures over 290MM patients with over 78% of a ll prescription claims and 60% of all medical claims. Medic
Slide 11: Real World PV Patient Treatment Data
Real World PV Patient Treatment Data 11 Evaluation of 28,306 PV Patients Treated in 2018 - 19 • Predominant treatment is phlebotomy, regardless of risk • Hydroxyurea is the most commonly used cytoreductive agent • Combination of hydroxyurea and phlebotomy commonly used to control HCT • Hematocrit no
Slide 12: 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 12 FERROPORTIN transports iron HEPCIDIN Inhibits ferroportin serum iron Transferrin delivers iron Splenic macrophage EXCESSIVE RB
Slide 13: Phase 2 Study of Rusfertide in PV Patients (REVIVE)
PART 1 (28 wks) PART 2 (up to 12 wks) PART 3 (52 wks 1 ) Dose Finding * Efficacy Evaluation * Randomized Withdrawal Open Label Extension * Phase 2 Study of Rusfertide in PV Patients (REVIVE) 13 GOAL: Maintain Hematocrit <45% ELIGIBILITY REQUIREMENTS: • Phlebotomy dependent PV patients diagnosed as p
Slide 14: Effect of Rusfertide on Phlebotomy Frequency in REVIVE Study
Effect of Rusfertide on Phlebotomy Frequency in REVIVE Study Phlebotomy only (N=31, 49%) Phlebotomy + cytoreductive (N=32, 51%) 14 Data as of September 30, 2021 Screening Part 1 – Dose Finding Part 2 – Blinded Withdrawal Part 3 – Open Label Extension Phlebotomy Last dose on study Pre - Treatment - 2
Slide 15: Baseline Characteristics of Study Participants in REVIVE Study
Baseline Characteristics of Study Participants in REVIVE Study Characteristics (n = 63) AGE Range 27 - 76 years (Mean = 56.3 yrs ) GENDER Females 18 (28.8%) Males 45 (71.4%) RISK Low 28 (44.4%) High 35 (55.6%) [Age based – 36.5%, Thrombotic events – 19.0%] DURATION SINCE PV DIAGNOSIS <1 yr 12 (19.0%
Slide 16: Rusfertide Controls HCT and Ferritin in REVIVE Study
Rusfertide Controls HCT and Ferritin in REVIVE Study 16 Hematocrit Ferritin Data as of September 30, 2021 Box whiskers extend up to 1.5 times interquartile range. Screening Part 1 – Dose Finding Part 2/3 – Blinded Withdrawal/OLE Part 3 – Open Label Extension
Slide 17: Improvement in MPN-TSS Scores Following Rusfertide
Data as of September 30, 2021 17 Improvement in MPN - TSS Scores Following Rusfertide in REVIVE Study 1.9 0.9 0.0 0.5 1.0 1.5 2.0 Baseline N=24 Week 28 N=24 Paried Mean Total Symptom Score Worst Level of Fatigue Problems with Concentration Itching - Pruritus 3.2 2.7 0 1 2 3 4 Baseline N=24 Week 28 N
Slide 18: REVIVE Adverse Events
• Most Drug related AEs were Grade 1 or 2 • No Grade 4 or 5 Events • SAEs: Syncope, peripheral artery aneurysm, gastroenteritis, chest pain, AML, squamous cell carcinoma (skin), melanoma & basal cell carcinoma • Injection site reaction (ISRs) were most common and associated with 28.1% of injections.
Slide 19: Select SAEs in Further Context
19 Select SAEs in Further Context 1 • A total of 168 patients have been treated with rusfertide to date: beta - thalassemia, hereditary hemochromatosis (HH), and polycythemia vera (PV) − Of these, 7 subjects with 8 observed cancer cases, inclusive of cases confirmed as pre - existing − Of the 89 PV
Slide 20: Skin Cancer Prevalence in Historical/General PV Population
Skin Cancer Prevalence in Historical/General PV Population 20 • A sub - analysis of the PV patient journey project with Symphony was conducted to determine the prevalence of skin cancers in the general PV population – Total PV population consisted of 28,306 patients – Observation window 2011 - 2019
Slide 21: Conclusions from Phase 2 REVIVE Study
Conclusions from Phase 2 REVIVE Study 21 Rusfertide therapy resulted in rapid, sustained and durable hematocrit control without clinically meaningful changes in white blood cell and platelet counts Rusfertide demonstrated similar efficacy in all categories of patients, independent of the PV patient
Slide 22: PACIFIC: Open-Label Phase 2 PV Study in High Hematocrit
PACIFIC: Open - Label Phase 2 PV Study in Subjects with high hematocrit (>48%) Full overview available at https://clinicaltrials.gov/ct2/show/NCT04767802 22 Patient met the WHO criteria for PV diagnosis and had a baseline hematocrit (HCT) >48%, and a history of ≥3 HCT values >48% in the prior year p
Slide 23: PACIFIC Phase 2 Study Therapeutic Phlebotomies
005 004 006 007 011 009 001 003 015 018 016 014 002 019 013 012 008 020 017 010 Weeks Subjects Data as of September 30, 2021 23 PACIFIC Phase 2 Study (High Hematocrit) Therapeutic Phlebotomies Prior to and on Rusfertide 52/F 47/M 69/F 62/M 41/M 60/M 49/F 63/M 53/F 55/M 58/M 57/M 46/M 53/M 63/M 41/M
Slide 24: Rusfertide Controls HCT and Reduces RBC Count in PACIFIC Study
Data as of September 30, 2021 24 Rusfertide Controls HCT and Reduces RBC Count in PACIFIC Study Rusfertide Rapidly Reduces RBC Count RBC (10^6/ uL ) Weeks 8 7 6 5 4 3 Wk 12 Baseline Wk 4 Wk 8 Wk 16 Wk 20 Wk 24 Wk 28 20 18 17 13 11 9 4 3 N Screening PTG - 300 Mean Rusfertide Rapidly Controls HCT Week
Slide 25: PACIFIC Adverse Events
• Most Drug related AEs were Grade 1 or 2 • One subject stopped treatment due to AE (Thrombocytosis without bleeding or thrombosis; Grade 4 according to investigator) • Injection site reaction (ISRs) were most common and associated with 68% of injections. All ISRs were transient, and no patient disc
Slide 26: Conclusions from PACIFIC High Hematocrit Study
Conclusions from PACIFIC High Hematocrit Study 26 Rusfertide induction therapy with twice weekly dosing is effective at rapidly achieving target hematocrit below 45% without phlebotomy in all PV patients. Rapid hematocrit control: <45% in 4 - 6 weeks, without a clinically meaningful change in platel
Slide 27: Rusfertide Phase 3 PV Study Design (VERIFY Study)
27 Enrollment Criteria: • Adult patients with PV per 2016 WHO Criteria • High risk and low risk patients • Patients requiring frequent phlebotomy • With or without cytoreductive therapy • Exclusion of patients with invasive cancer in prior 5 years Primary Endpoint: • Absence of phlebotomy eligibilit
Slide 28: Randomized, Double-blind, Placebo-Controlled Phase 3 PV Study (VERIFY)
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) Part 2 Long Term Safety Follow - up ( Weeks 52 - 156) Screening (Up to 4 Weeks) Randomized, Double - blind, Placebo - Controlled Phase 3 PV Study (VERIFY
Slide 29: Polycythemia Vera Treatment Options and Potential Commercial Opportunity
Illustrative rusfertide target Polycythemia Vera 29 Current treatment options and potential commercial opportunity *Newly FDA approved, undergoing U.S. commercial launch; uncertain place in the therapeutic paradigm at present **~5,300 patients treated with Jakafi; uncertain of Besremi population due
Slide 30: Rusfertide Market Preparation: PV Indication
Rusfertide Market Preparation: PV Indication Intend to Demonstrate Clinical & Economic Value Before Approval 30 Value Proposition Market Access HEOR Competitive Landscape Positioning Strategy Prescriber Education Distribution Channels Patients Prescribers Payers Patient access Pricing & Reimbursemen
Slide 31: Hereditary Hemochromatosis (HH) Disease Prevalence and Treatment
Hereditary Hemochromatosis (HH) 31 Disease Prevalence and Treatment If untreated, iron overload can cause hepatomegaly, diabetes mellitus, skin hyperpigmentation, cardiomyopathy, diastolic dysfunction, heart failure, cirrhosis, etc . Iron overload disease Unmet medical need in specific subpopulation
Slide 32: Proof of Concept Phase 2 Study in Hereditary Hemochromatosis
Proof of Concept Phase 2 Study in Hereditary Hemochromatosis 32 SCREENING MONTH 1 MONTH 2 MONTH 3 MONTH 4 MONTH 5 MONTH 6 Pre - study Phlebotomy and Liver MRI • Six - month, open - label study in 16 HH patients in maintenance phase of iron depletion • Stable pre - study phlebotomy for ≥6 months; req
Slide 33: Hereditary Hemochromatosis: Summary of Results and Next Steps
Hereditary Hemochromatosis 33 Summary of Results in HH and Next Steps • Significantly reduction in number of phlebotomies • Maintained liver iron content • Lowered serum iron and TSAT • Well tolerated • All treatment - emergent AEs were Grade 1 or 2 Next Steps • Market assessment underway; severity
Slide 34: PN-943 and PN-235 IL-23 Receptor Antagonists
PN - 943 and IL - 23 Receptor Antagonists Oral Targeted Investigational Therapies for IBD and non - IBD indications 34
Slide 35: IBD: Paradigm Shift Toward Targeted Oral and Combination Therapy
IBD: Paradigm Shift Toward Targeted Oral and Combination Therapy 35 A growing multi - billion dollar market • Injectable TNF mAbs – Blockbusters – Humira ® & Remicade ® • Significant room for improvement – Low response rates / loss of response – Safety concerns - black box warnings TNF mAbs dominate
Slide 36: Oral, Gut-Restricted α4β7 Integrin Peptide Antagonists: PN-943
Oral, Gut - Restricted, a 4 b 7 - Integrin Peptide Antagonists: PN - 943 36 Fully Owned and Validated Asset and Approach Vs. Briskin M, et al Am J Pathol. 1997;151:97 - 110 Clinically Validated, IBD Specific Target • T cell homing regulated by α4β7 integrin and MAdCAM - 1 interaction • MAdCAM - 1 ex
Slide 37: PN-943: First-in-Class Oral α4β7 Integrin Antagonist
37 PN - 943 superior to first generation PTG - 100 • In vitro potency and binding kinetics with similar robust selectivity • Blood PD effects of local target engagement in 3 species with oral stability and limited blood exposure • Efficacy in rodent colitis model PN - 943: First - in - Class Oral a
Slide 38: PN-943 vs. PTG-100: Blood %RO Based Clinical Proof-of-Concept
PN - 943 vs. PTG - 100: Blood %RO based Clinical Proof - of - Concept Ph1 NHV Single Ascending Dose Study Ph2A Study UC PTG - 100 900 mg Histologic Remission 44% (7/16) Clinical Remission* 16% (3/19) *based on blinded endoscopic re - reads * Clinical remission: SFS ≤1, RBS = 0, ESS ≤1 Established 74
Slide 39: PTG-100 Ph2A Efficacy Similar to Other IBD Targeted Therapy Drugs
PTG - 100 Ph2A Efficacy Similar to Other IBD Targeted Therapy Drugs 39 Oral/S1P1 17.6 15.2 15.3 12.3 16.9 15.8 6 6.2 0 2.7 5.4 4.8 11.6 9 15.3 9.6 11.5 11 0 2 4 6 8 10 12 14 16 18 20 Tofacitinib Ozanimod Etrolizumab SHF-647* Entyvio PTG-100 % Patients in Clinical Remission Active Placebo Delta a4b7
Slide 40: IDEAL: PN-943 Phase 2 UC Study
IDEAL: PN - 943 Phase 2 UC Study 40 Part - 1: Induction Part - 2: Extended Treatment Period 5 weeks 12 weeks 40 Weeks Week 52 Randomize (n=150) Placebo BID (n=50) Active Drug 450 mg BID (n=50) Active Drug 150 mg BID (n=50) PN - 943 Adult Patients with UC N≈150 Eligibility: • Moderate – Severe UC • 3
Slide 41: The Outcome of Phase 2 IDEAL Study will Inform Phase 3 Decisions
The Outcome of Phase 2 IDEAL study will Inform Phase 3 decisions • Phase 2 data in UC with various candidates spanning different mechanism of actions – Large confidence intervals, influenced by study design, duration, size, demographics, & criteria – Phase 2 outcomes has generally predicted efficacy
Slide 42: Oral, IL-23 Receptor Specific Peptide Antagonist: PN-235 Janssen Partnership
Oral, IL - 23 Receptor Specific Peptide Antagonist: PN - 235 42 Janssen Partnership IL - 23R IL - 12R β 1 IL - 12R β 2 IL - 12R β 1 Stelara ® : Blocks both IL - 23 & IL - 12 pathways IL - 23R Antagonist : Blocks IL - 23 receptor & IL - 23 pathway p19 antibody : Blocks IL - 23 pathway p40 p40 p19 p35
Slide 43: Janssen FRONTIER Phase 2b Plaque Psoriasis Study
Janssen FRONTIER 1 Phase 2b Plaque Psoriasis ( PsO ) Study 43 PN - 943 Adult Patients with PP N≈240 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
Slide 44: Protagonist Team and Financials
44 44 PROTAGONIST THERAPEUTICS Protagonist Team and Financials
Slide 45: Protagonist Team
Protagonist Team 45 Experience & Expertise in Drug Discovery, Clinical Development, and Commercialization Dinesh Patel, PhD President & CEO David Liu, PhD Chief R&D Strategy Officer Samuel Saks, MD Clinical Development Advisor Suneel Gupta, PhD Chief Development Officer Asif Ali (announced) Chief Fi
Slide 46: Financial Highlights
Financial Highlights 46 Financial resources forecast extends through full year 2024 CASH & SECURITIES a s of December 31, 2021 CASH & SECURITIES provide financial resources forecast through full year 2024* SHARES OUTSTANDING as of February 15, 2022 2024 48.4M $326.9M *This includes our initial CMC i
Slide 47: Upcoming Catalysts in 2022 and Beyond
47 Products Anticipated Events of 2022 2023 Q1 Q2 Q3 Q4 Rusfertide • VERIFY: Ph3 250 patient PV study initiation • REVIVE: Ph2 PV study (300 - 04) continuation • Ph3 enrollment completion (1H) • Ph2 randomization results (Q1) • 2 nd indication: HH market opportunity and next steps PN - 943 • Ph3 UC
Slide 48: Thank you
& Protagonist Therapeutics Thank you 48
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