Protagonist Therapeutics, Inc. · NASDAQ:PTGX
Protagonist Therapeutics — Investor Presentation (November 2022)
35 slides from Protagonist Therapeutics's investor presentation, November 2022
Slide 1: Company Overview
COMPANY OVERVIEW Dinesh V. Patel, PhD | President & CEO November 2022 1
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
Slide 3: Protagonist Therapeutics
Protagonist Therapeutics Ongoing Ph3 Study of Rusfertide in PV | Collaboration with Janssen Toward Oral IL-23R Antagonist • Robust, advancing peptide • Co-Development partnership portfolio therapeutic candidate portfolio earned $112.5 Million in milestone addressing indications with multi-billion- p
Slide 4: Peptide-based Medicines
Protagonist Therapeutics Peptide-based Medicines Discovering novel peptide therapeutics through a proprietary technology platform and developing them to address unmet medical needs POTENCY 1 Computational 3 Vectrix, Clusters 2 Peptide Chemistry CLINICAL ASSETS SAR, Leads Phage Libraries IN LATE-STAG
Slide 5: Product Portfolio
Product Portfolio Addressing Unmet Needs in Multiple Indications with Multi-Billion Dollar Market Potential Programs Candidates Study Phase 1 Phase 2 Phase 3 Key Milestones HEMATOLOGY & BLOOD DISORDERS POLYCYTHEMIA VERA (PV) • ~250 patient, randomized, double-blind, placebo- VERIFY PV Ph3 trial cont
Slide 6: Rusfertide (PTG-300): Hepcidin Mimetic
Rusfertide (PTG-300): Hepcidin Mimetic To Potentially Address Unmet Needs in Polycythemia Vera
Slide 7: Polycythemia Vera
Polycythemia Vera Disease Background Myeloproliferative neoplasm characterized by excessive production of red blood cells (RBCs) • Elevated hematocrit (HCT) is a hallmark of the disease, indicating overproduction of RBCs Treatment goal is to control Serious, chronic disease associated with increased
Slide 8: Rusfertide: Mechanistic Rationale for Potential Treatment of PV
Rusfertide: Mechanistic Rationale for Potential Treatment of PV Polycythemia Vera MOA of rusfertide FERROPORTIN transports iron RUSFERTIDE Elevated Normalized Hematocrit Hematocrit Splenic FERROPORTIN macrophage RBC PRODUCTION HEPCIDIN EXCESSIVE RBC PRODUCTION Inhibits ferroportin 45% 45% SERUM IRON
Slide 9: Rusfertide for Polycythemia Vera
Rusfertide for Polycythemia Vera Three Clinical Studies Have Generated Positive Data Ph3 VERIFY, Ph2 REVIVE, Ph2 PACIFIC • Phase 3 VERIFY Study: − Study execution continues with enrollment completion expected in 2H 2023 − Agreed upon Phase 3 VERIFY protocol with the FDA and CHMP (EU) − Agreements in
Slide 10: Randomized, Double-blind, Placebo-Controlled Phase 3 PV Study (VERIFY)
Randomized, Double-blind, Placebo-Controlled Phase 3 PV Study (VERIFY) Ongoing VERIFY Study of N~250 Subjects Part 1a Part 1b Part 2 Safety Screening (Up to 4 Double Blind (Weeks 0-32) Follow-up Durability of Response Long Term Safety Follow-up (4 W eeks) Weeks) Dose Titration Primary Efficacy (Week
Slide 11: Phase 2 Study of Rusfertide in PV Patients (REVIVE)
Phase 2 Study of Rusfertide in PV Patients (REVIVE) GOAL: Maintain Hematocrit <45% Clinical Proof-of-Concept Study with Add-On PART 1 (28 wks) PART 2 (up to 12 wks) PART 3 (52 wks1) Dose Finding* Efficacy Evaluation* Randomized Withdrawal Open Label Extension* 80 mg Dose ± Titration Fixed Active/Pla
Slide 12: Baseline Characteristics of Study Participants in REVIVE Study
Baseline Characteristics of Study Participants in REVIVE Study Characteristics (n = 70) AGE THERAPIES Range 27-77 years (Mean = 57.3 yrs) PHL only 34 (48.6%) GENDER PHL + HU 21 (30.0%) Females 21 (30.0%) PHL + IFN 8 (11.4%) Males 49 (70.0%) PHL + RUX 3 (4.3%) RISK PHL +Multiple Agents 4 (5.7%) Low 2
Slide 13: Meaningful Reduction in Phlebotomy Frequency Following Rusfertide Administration
Meaningful Reduction in Phlebotomy Frequency Following Rusfertide Administration Phlebotomy Only (n=34) Open Label Extension Randomized Withdrawal Data cutoff: May 11, 2022 13
Slide 14: Meaningful Reduction in Phlebotomy Frequency Following Rusfertide Administration
Meaningful Reduction in Phlebotomy Frequency Following Rusfertide Administration Phlebotomy and Cytoreductives (n=36) Open Label Extension Randomized Withdrawal Data cutoff: May 11, 2022 14
Slide 15: REVIVE Study: Rusfertide Treatment Suspension Led to Loss of Effect
REVIVE Study: Rusfertide Treatment Suspension Led to Loss of Effect Data Provides Additional Evidence Supporting Clinical Efficacy 0.0001 <0.0001 Treatment Restart Restores Benefit 0.0094 <0.0001 <0.0001 46 Post Rusfertide Phlebotomy Rate (/week) 0.3 <0.0001 Rusfertide Restart Hematocrit (%) 44 42 0
Slide 16: Rusfertide Controlled HCT and Ferritin in REVIVE Study
Rusfertide Controlled HCT and Ferritin in REVIVE Study Hematocrit Ferritin Screening Part 1 – Dose Finding Part 2/3 – Blinded Withdrawal/OLE Part 3 – Open Label Extension Error bars identify 95% confidence interval for the mean. Data as of May 11, 2022 16
Slide 17: Improvement in Symptom Scores Following Rusfertide in REVIVE Study
Improvement in Symptom Scores Following Rusfertide in REVIVE Study Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-TSS) Problems with Concentration Total Symptom Score Worst Level of Fatigue Itching-Pruritus Data as of May 11, 2022 17
Slide 18: Rusfertide Lowered Hematocrit Levels Before and After Drug Suspension Period
Rusfertide Lowered Hematocrit Levels Before and After Drug Suspension Period PACIFIC Study in PV Patients with High HCT (>48%), n=14* Rusfertide Rusfertide Suspension Restart Suspension Restart Error bars identify 95% confidence interval for the mean. Data cutoff: May 11, 2022, *Subjects with comple
Slide 19: Adverse Events Following Rusfertide in Patients with PV
Adverse Events Following Rusfertide in Patients with PV 19 REVIVE and PACIFIC Studies Most treatment related AEs were Grade 1 or 2 AE n (%) Preferred term • Injection site reaction (ISRs) were most common and associated with 33% of injections. All ISRs were Total number of Subjects 90 transient, and
Slide 20: Potential Commercial Opportunity
Potential Commercial Opportunity PV Patients Primarily Requiring HCT Control Diagnosed & Treated ~100,000 Patients in the U.S. RBC-Focused Patients ~90,000 Patients whose primary concern is RBC and HCT levels Patients with HCT>45% ~70,000 Based on internal metrics and third-party research 20
Slide 21: Elevated Hematocrit Results in Greater Risk of Death
Elevated Hematocrit Results in Greater Risk of Death Death from CV or Major Thrombotic Events Endpoint • Patients randomized to <45% (Low) or 45 – 50% (High) HCT group Probability of Remaining Event-free 1.00 • At a median of 31 months, 9.8% of the High HCT group met the primary endpoint vs 2.7% in
Slide 22: Real World PV Patient Treatment Data Suggests HCT Control as Pressing Need
Real World PV Patient Treatment Data Suggests HCT Control as Pressing Need Evaluation of More Than 25,000 PV Patients • Predominant treatment to control HCT is phlebotomy, regardless of patients’ risk • Hydroxyurea is the most common cytoreductive agent, often used in combination with phlebotomy Tre
Slide 23: Polycythemia Vera: Current Treatment Options and Potential Commercial Opportunity
Polycythemia Vera Current Treatment Options and Potential Commercial Opportunity Illustrative rusfertide target Disease Severity Disease Stage Early / low burden Moderate burden Late / high burden PV population ~20% of PV population ~60% of PV population ~20% of PV population Current treatment Infre
Slide 24: PN-235: IL-23 Receptor Antagonist
PN-235: IL-23 Receptor Antagonist Oral Targeted Investigational Therapy for Psoriasis and IBD indications 24
Slide 25: Oral, IL-23 Receptor Specific Peptide Antagonist: PN-235
Oral, IL-23 Receptor Specific Peptide Antagonist: PN-235 Janssen Partnership Objective p19 antibody: Stelara®: Blocks both • Extend the Stelara® and Tremfya® franchise and transition from injectable Blocks IL-23 pathway IL-23 & IL-12 pathways to oral targeted therapy p19 p40 p35 p40 • Stelara® and T
Slide 26: Additional Key Aspects of the Janssen-Protagonist Collaboration
Additional Key Aspects of the Janssen-Protagonist Collaboration Multiple studies A range of PN-235 of IL-23 pathway indications Indication agnostic Extended research term development milestones No PTGX cost share of 3 years for Janssen 26
Slide 27: Milestones Status and Outlook
Milestones Status and Outlook 2023 $112.5m in development milestones have been achieved $855m approximate amount of total future development and sales milestones for which Protagonist remains eligible For the near term, the Company is eligible for a $10 million milestone payment in connection with t
Slide 28: Basic Biology of the IL-12/23 and IL-23 Cytokine Targets
Basic Biology of the IL-12/23 and IL-23 Cytokine Targets Selective blockade of IL-23 signaling by targeting p19 Guselkumab Tildrakizumab Ustekinumab Risankizumab Mirikizumab Targeting IL-23p19; blocks IL-23 Targeting p40; blocks both IL-12 & IL-23 • Th17 pathway inhibition • Inhibits both Th1 and Th
Slide 29: PN-235 Rationale
PN-235 Rationale Background Context Blockade of the IL-12 and IL-23 pathways, as well as the downstream Th17 pathway, have resulted in unprecedented efficacy in psoriasis • There is intense interest in oral IL-23 inhibitors to replace biologics • JAK inhibitors have black box warnings; Tyk2 inhibito
Slide 30: A Safe & Efficacious Oral Medicine Would Revolutionize Therapeutic Options
A Safe & Efficacious Oral Medicine Would Revolutionize Therapeutic Options Access new patients and diseases Enable novel combinations • Enables access to more patients globally • Opens potential option of oral drug as maintenance after biologic induction • Expands to more moderate stages of disease
Slide 31: Protagonist Executive Leadership Team and Financials
Protagonist Executive Leadership Team and Financials 31
Slide 32: Protagonist Team
Protagonist Team Experience & Expertise in Drug Discovery, Clinical Development, and Commercialization Dinesh Patel, PhD President & CEO David Liu, PhD Chief R&D Strategy Officer Arturo Molina, MD, MS Chief Medical Officer Samuel Saks, MD Clinical Development Advisor Suneel Gupta, PhD Chief Developm
Slide 33: Financial Highlights
Financial Highlights Financial Resources Forecast Extends Through Full Year 2024* $267.4M 2024 49.2M CASH & SECURITIES CASH & SECURITIES SHARES OUTSTANDING as of Sept. 30, 2022 provide financial resources as of Sept. 30, 2022 forecast through full year 2024* *Based on our current operating plan and
Slide 34: Major catalysts ahead
Major catalysts ahead 2023 stands to be a transformative year for Protagonist, with two key events in view Key events in 1H and 2H 2023 (estimated): Q1 Q2 Q3 Q4 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec REVIVE FRONTIER 1 VERIFY Randomization Data Phase 2 Data Readout Enrollment Completion Read
Slide 35: Thank you
Protagonist Therapeutics Thank you 35
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