Protagonist Therapeutics, Inc. · NASDAQ:PTGX
Protagonist Therapeutics — Corporate Update (September 2020)
52 slides from Protagonist Therapeutics's corporate update, Sep 11, 2020
Slide 1: PTG-300 Opportunity Update
PTG - 300 Opportunity Update Dinesh V. Patel, PhD President & CEO 1 September 11, 2020
Slide 2: Forward Looking Statements
2 Forward Looking Statements This presentation contains forward - looking statements of Protagonist Therapeutics, Inc . (Protagonist) that involve substantial risks and uncertainties . All statements other than statements of historical facts contained in this presentation, including statements regar
Slide 3: Protagonist Therapeutics: Peptide Based Innovative Medicine
Protagonist Therapeutics: Peptide Based Innovative Medicine • Three clinical assets – De novo discovery using peptide technology platform – Multi billion - dollar portfolio potential • Four Clinical PoC studies – PTG - 300: ▪ PV as the 1st proposed indication for pivotal ▪ HH Ph2 study under progres
Slide 4: PTG-300 Opportunity Update: Key Messages
PTG - 300 Opportunity Update • Significant unmet need in Polycythemia Vera (PV) • Continued progress with PTG - 300 in expanded Ph 2 POC study • Building a hepcidin mimetic franchise 4 Key Messages
Slide 5: Agenda
Agenda 5 Agenda Overview/Introductions Dinesh Patel, PhD • President & CEO Suneel Gupta, PhD • Chief Development Officer Polycythemia Vera Disease and Current Treatments Ron Hoffman, MD • Director of the Myeloproliferative Diseases Program • The Icahn School of Medicine at Mount Sinai Introduction t
Slide 6: Polycythemia Vera Treatment
Polycythemia Vera Treatment Ron Hoffman, MD Icahn School of Medicine at Mount Sinai 6
Slide 7: What is Polycythemia Vera?
What is Polycythemia Vera? • Polycythemia Vera (PV) is a specific type of myeloproliferative neoplasm primarily characterized by the overproduction of red blood cells – PV is typically caused by Janus Kinase 2 (JAK2) mutation – Although the JAK2 mutation drives increases in all cell types, the great
Slide 8: Diagnosis and Treatment Goals of Polycythemia Vera
Diagnosis and Treatment Goals of Polycythemia Vera • Elevated hematocrit or a thrombotic event often initiates the diagnosis – Followed by blood test to confirm the presence of a JAK2 mutation • Thrombotic events such as stroke and heart attack present the greatest risk to PV patients – Patients are
Slide 9: Goal of PV Treatment: Keep HcT <45%
9 Goal of PV Treatment: Keep HcT <45% • NCCN Guidelines call for maintaining patient’s hematocrit below 45% 1 • Maintaining hematocrit < 45% reduces risk of stroke, myocardial infarction and death compared to maintaining hematocrit 45% to 50% 2 Low Risk < 60 years No thrombotic events High Risk > 60
Slide 10: CYTO-PV Study
CYTO - PV Study • Patients randomized to < 45% (Low) or 45 – 50% (High) • At a median of 31 months, 9.8% of the High HcT group met the primary endpoint vs 2.7% in the Low HcT group • Patients with hematocrit between 45 - 50% were ~4 times more likely to die from cardiovascular causes or major thromb
Slide 11: Treatment of PV: Therapeutic Phlebotomy
Treatment of PV • Phlebotomy is the standard - of - care treatment for low risk PV patients – Low risk patients who require frequent phlebotomies (more than ~5 - 6 in one year) to keep their HcT below 45% also receive cytoreductive therapy in addition to phlebotomy – Also used in high risk patients
Slide 12: Treatment Challenges: Phlebotomy
Treatment Challenges • Phlebotomy works in part by removing iron – 95% of PV patients are iron deficient at diagnosis with iron deficiency worsening after repeated and/or frequent phlebotomies. – Symptoms include: cognitive impairment, debilitating fatigue, decreased physical performance, decreased
Slide 13: Treatment of PV: Cytoreductive Agents
Treatment of PV • Although never studied in randomized clinical trials HU is first - line treatment for PV • Cytoreductive agents like hydroxyurea work through progenitor cells and reduce all blood cell types indiscriminately (RBC’s, WBCs and platelets) • High risk patients are started on phlebotomy
Slide 14: Treatment Challenges: Cytoreductive Therapies
Treatment Challenges • Cytoreductive therapies reduce all cells and this can lead to thrombocytopenia and bleeding disorders • The main side effects of HU include bone marrow suppression, low red cell, white cell and platelet counts, hair loss, nausea, vomiting, diarrhea, mucocutaneous ulcers and an
Slide 15: Treatment of PV: Jakafi (ruxolitinib)
Treatment of PV • Ruxolitinib inhibits Janus kinase 2 (JAK 2), a non - receptor tyrosine kinase involved in the production of red blood cells • Indicated in PV for adults who have an inadequate response, or intolerant to hydroxyurea • In Phase 3, a signicantly greater proportion of ruxolitnib patien
Slide 16: Treatment Challenges: Jakafi
Treatment Challenges • Indicated only in adults who have had an inadequate response to or are intolerant to hydroxyurea • Most common hematological adverse events in ruxolitinib group in phase 2 trial – Grade 1 anemia - 53 % of patients – Thrombocytopenia - 27 % of patients • Most frequent non - hem
Slide 17: Conclusions
Conclusions • Physician and patient treatment management goal is to decrease thrombotic events by maintaining HcT below 45% • Phlebotomy alone or in combination with cytoreductive therapy is the most common treatment • Frequent phlebotomy can often lead to iron deficiency symptoms including cognitiv
Slide 18: Introduction to Symphony Data
Introduction to Symphony Data Tracy Woody EVP, Corporate Strategy 18
Slide 19: Patient Journey Objectives
Patient Journey Objectives • Gain a sense of how patients are treated following a diagnosis of PV • Better understand how current therapies are used to manage PV patients vs. guidelines – Phlebotomy – Cytoreductive therapies – Combination treatment • Determine if patients HcT was being adequately co
Slide 20: Symphony Health Claims Overview
Symphony Health Claims Overview • PV is managed by a combination of phlebotomy, prescription medications, and lab results • To optimally address the unmet need in PV all of these therapies need to be analyzed over a period of time • The Symphony data includes de - identified, patient linked prescrip
Slide 21: Methodology and Patient Cohorts
Methodology and Patient Cohorts • Patients with two confirmed diagnosis and receiving treatment over 2 - year period • A minimum of 2 HcT test post treatment initiation • Representative of treated PV population Symphony Patient Journey, August 2020 Post - Stability 28,306 pts. > 2 HcT 4,264 pts. 21
Slide 22: PV: Patient Analytics
22 Protagonist Therapeutics PV: Patient Analytics Srdan Verstovsek , MD, PhD MD Anderson Cancer Center
Slide 23: Introduction
Introduction 23 1 Verstovsek, S. et al, Blood (2019) 134 (Supplement_1): 1659. • Opportunity to evaluate data from a large population of patients to assess real world treatment patterns • Similar approach as Optum database study that also uncovered treatment gaps 1 • Diagnosis via ICD - 10; all pati
Slide 24: Patient Demographics and Risk Stratification
Patient Demographics and Risk Stratification 24 All Treated Patients (n = 28,306) Total Treated Patients 30% 5% 15% 51% Age < 60 and No Prior Thrombotic Event Age < 60 and Prior Thrombotic Event Age >=60 and Prior Thrombotic Event Age >=60 and No Prior Thrombotic Event Risk Stratification • Median p
Slide 25: Treatments Over Two-Year Period
Treatments Over Two - Year Period • 67% of patients started with phlebotomy alone regardless of risk • 77% of phlebotomy patients did not change treatments over the course of two years 25 All Treated Patients (n = 28,306) Treatment Initiation Treatment Change 1 67% PTB, 18,942 25%, HU, 7,202 7%, PTB
Slide 26: Treatments Over Two-Year Period: High Risk Patients
Treatments Over Two - Year Period • Although considered high risk, 60% patients still started with phlebotomy alone • The majority (73%) did not change treatments over the course of two years 26 High Risk Patients (n= 19,933) Treatment Initiation Treatment Change 1 73%, No Change, 8,717 17%, HU, 2,0
Slide 27: Hematocrit not Being Managed According to Guidelines
Hematocrit not Being Managed According to Guidelines • Poor control of HcT is evident by almost half of patients having HcT above 50% at least once during observation period • Only 22% had all HcT tests below 45%, an optimal result Treated Patients with ≥2 HcT Tests (n = 4,264) 27 *Patient HcT group
Slide 28: Treatment Challenges with Phlebotomy
Treatment Challenges with Phlebotomy • 17% of patients treated with phlebotomy alone had ≥6 phlebotomies a year • 42 % of phlebotomy treated patients with 6 or more annual phlebotomies still h ad all HcT levels above 45% 28 HcT Distribution – PTB Only with ≥6 Annualized PTB Phlebotomy Count Distribu
Slide 29: Treatment Challenges with Hydroxyurea + Phlebotomy
• 44% of patients treated with HU + phlebotomy had ≥4 or more phlebotomies a year • 19% on combination who had ≥ 4 phlebotomies still had all HcT tests above 45% 29 HcT Distribution – PTB + HU with ≥4 Annualized PTB Phlebotomy Count Distribution for PTB + HU (n = 474) Treatment Challenges with Hydro
Slide 30: Thrombotic Events in PV Patients
Thrombotic Events in PV Patients 30 All Treated Patients (n = 28,306) Risk Group Total Patient Count Patient with TE Post Treatment Initiation* % of TE n n % Low Risk Patients Age < 60 and No Prior TE 8,373 629 8% High Risk Patients All High - Risk Patients 19,933 3,920 20% Patients with no Prior TE
Slide 31: Conclusions
Conclusions • Despite advancements made in the field of PV there is opportunity for significant improvement • New differentiated interventions are potential part of better treatment solutions • Hematocrit is a central theme in the treatment of PV with the goal of maintaining patients below 45% to re
Slide 32: Market Opportunity
32 Market Opportunity Tracy Woody EVP, Corporate Strategy
Slide 33: PTG-300 Market Opportunity for PV
PTG – 300 Market Opportunity for PV • There are approximately 160,000 people in the United States living with PV 1 • Growing market with an average of 14,000 new patients diagnosed annually • Majority of diagnosed patients are treated – PV patients on average see their physician 6 times annually – E
Slide 34: PV Treatment Regimens
PV Treatment Regimens • Predominant treatment is phlebotomy • Hydroxyurea is most commonly used cytoreductive agent • Combination of phlebotomy and hydroxyurea commonly used to control HcT 34 Symphony Treated Patients 2018 - 2019 Treatments at End of Two - Year Index Period Symphony Patient Journey
Slide 35: Polycythemia Vera Newly Diagnosed Patients
Polycythemia Vera Newly Diagnosed Patients 12,524 15,421 14,649 14,601 0 2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 18,000 2016 2017 2018 2019 35 Symphony Research 2020
Slide 36: Hydroxyurea Prescriptions
Hydroxyurea Prescriptions 14,569 15,119 15,700 16,351 82,197 84,335 86,600 87,132 0 10,000 20,000 30,000 40,000 50,000 60,000 70,000 80,000 90,000 100,000 2016 2017 2018 2019 Unique HU PV Patients Total HU Rx's • Overall prescriptions relatively flat over the past three years with a ~ 3% increase •
Slide 37: Jakafi Growth Strongest in Polycythemia Vera
Jakafi Growth Strongest in Polycythemia Vera 1,800 2,800 3,800 5,000 5,800 6,300 7,000 7,800 100 300 500 1,800 2,500 3,800 4,000 5,000 0 1000 2000 3000 4000 5000 6000 7000 8000 9000 Q3 2012 Q3 2013 Q3 2014 Q3 2015 Q3 2016 Q3 2017 Q3 2018 Q3 2019 Jakafi Total Patients on Therapy Myelofibrosis PV 37 M
Slide 38: Jakafi Focused Effort Generates Meaningful Revenue
Jakafi Focused Effort Generates Meaningful Revenue • 2019 US sales approximately $700 million in PV alone – Approximately 5,000 patients in 2019 – Roughly 5% of US treated patients • Concentrated physician target of 15,000 Heme/ Oncs that can be reached with small sales force • Patients average 6 vi
Slide 39: Current Treatment Paradigm
39 Current Treatment Paradigm Phlebotomy • Patients report a burden to their QOL • Patients report managing HcT can cause stress & anxiety 1 • Frequency can lead to iron deficiency Phlebotomy +/ - HU or Interferon • Difficult side - effect profile • Some patients reluctant to use chemotherapeutic ag
Slide 40: PV Market
PV Market • Large portion of the treated patient population appears to have imperfect control of HcT • Signal of unmet need, room for an agent focused on HcT control • We will continue to refine and identify the most appropriate segments 40 US Patients ~160K ~100K ~90K ~70K Patient Prevalence 1 Diag
Slide 41: PTG-300 Potential Positioning
PTG - 300 Potential Positioning • Significant challenges with current standards • Substantial population experiencing uncontrolled hematocrit – More than 70% were not reaching the NCCN guideline of HcT of below 45%, – 55% of phlebotomy patients are not being managed to guidelines – Of patients were
Slide 42: PTG-300 Clinical Update
PTG - 300 Clinical Update Sam Saks, MD Chief Medical Officer 42
Slide 43: PTG-300 Phase 2 Study in Polycythemia Vera Patients
PTG - 300 Phase 2 Study in Polycythemia Vera Patients 43 Clinical ‘Proof of Concept’ Study Design • Safety, dose finding and efficacy evaluation study • Inclusion criteria: ≥3 phlebotomies in past 6 months • Key endpoints – Safety – Maintain hematocrit <45% – Reduction in phlebotomies – Symptom scor
Slide 44: PTG-300 Phase 2, Part 1 Dose Finding Study
PTG - 300 Phase 2, Part 1 Dose Finding 28 Week Study • All dose compliant patients were phlebotomy free with persistent control of hematocrit levels to <45% – n=6, 4 to 28 weeks of treatment • Ferritin levels increased to normal levels in most patients • Safety profile: low rates of injection site r
Slide 45: PTG-300 Polycythemia Vera Study Investigators at Sites Across the U.S.
45 PTG - 300 Polycythemia Vera Study Investigators at Sites Across the U.S. Cancer Specialists of North Florida, FL • Dr. Ayed Ayed MD Anderson Cancer Center, TX • Dr. Srdan Verstovsek Mt. Sinai School of Medicine, NY • Dr. Ronald Hoffman Moffitt Cancer Center, FL • Dr. Andrew Kuykendall Univ. of Ka
Slide 46: PTG-300 Phase 2 Study Progress to Date
PTG - 300 Phase 2 Study Progress to Date • Expanded study to 50 patients and increased the number of study sites – Patients on either phlebotomy alone or in combination with stable doses with hydroxyurea , interferon or Jakafi – International sites added to the study • Enrollment of 50 patients by m
Slide 47: PTG-300 Hepcidin Mimetic: MoA and New Opportunities
47 PTG - 300 Hepcidin Mimetic: MoA and New Opportunities David Liu, PhD Chief Scientific Officer, Head of R&D
Slide 48: PTG-300 Mechanism of Action
45 High Hematocrit Liver Spleen Macrophage Bone Marrow STORED IRON Ferroportin (open) PV: Excess RBC Production PTG - 300: Reduces RBC Production Transferrin (TF) Iron (Fe) TF - FE Erythroblast JAK2 Red Blood Cell Normal Hematocrit Liver Spleen Macrophage Bone Marrow STORED IRON Ferroportin (closed)
Slide 49: PTG-300: Potential Indications
PTG - 300: Potential Indications • Control of excessive RBC with a high demand for iron – Primary genetic: ▪ Polycythemia Vera ▪ Idiopathic erythrocytosis – Secondary pulmonary ▪ Chronic obstructive pulmonary disease (COPD) ▪ Cor pulmonale • Control of iron imbalance in organs and tissues – Heredita
Slide 50: Expansion of Hepcidin Franchise
Expansion of Hepcidin Franchise • Discovery of oral hepcidin mimetic – Achieved preclinical PoC with lead peptide and continuing optimization – Intend to submit abstract to a major medical conference in 2020 • Expanding IP for PTG - 300 and Structural Analogs – 8 total Composition - of - Matter pate
Slide 51: Panel Q&A
& Protagonist
Slide 52: Concluding Remarks
PTG - 300 Opportunity Update • Significant unmet need in Polycythemia Vera (PV) • Continued progress with PTG - 300 in expanded Ph 2 POC study • Building a hepcidin mimetic franchise 52 Concluding Remarks
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