Protagonist Therapeutics, Inc. · NASDAQ:PTGX

Protagonist Therapeutics — Investor Presentation (January 2018)

32 slides from Protagonist Therapeutics's investor presentation, Jan 8, 2018

  1. Slide 1: Forward Looking Statements

    Forward Looking Statements This presentation contains forward-looking statements of Protagonist Therapeutics, Inc. (Protagonist). All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial pos

  2. Slide 2: Proprietary Technology Platform for Discovering Peptide Therapeutics

    Protagonist Therapeutics Proprietary Technology Platform for Discovering Peptide Therapeutics Technology Platform Proprietary Peptide Technology Platform • De novo discovery of peptides that match the potency of biologics - PPI targets • Option of engineering oral stability Assets Vectrix Clusters •

  3. Slide 3: Peptide Drugs to Address Unmet Medical Needs

    Protagonist Therapeutics Peptide Drugs to Address Unmet Medical Needs • • IBD: Multi-billion dollar market opportunity Oral peptides for IBD targets clinically validated by injectable mAbs 1. PTG-100 Ph 2b UC •  Integrin antagonist 2. PTG-200 Ph 1 • IL-23R antagonist • Partnership with Janssen V

  4. Slide 4: Team Experience & Expertise in Drug Development

    Protagonist Team Experience & Expertise in Drug Development 5 Dinesh Patel, PhD President & CEO David Liu, PhD CSO, Head of R&D Richard Shames, MD CMO Thomas O’Neil CFO Pat Murphy SVP, Regulatory & QA Thamil Anamalai, MSc, MPhil VP, Preclinical Development Ashok Bhandari, PhD VP, Chemistry Abha Bomm

  5. Slide 5: Peptide-based Therapeutics are on the Rise

    Peptide-based Therapeutics are on the Rise ‘Oral Peptides’ vs ‘Injectable Antibodies’ & side effects • Up to 80% new targets are ‘undruggable’ by small molecules –Protein-protein interaction (PPI) targets Antibodies vs peptides for ‘undruggable’ PPI targets –Oral peptides offer strong potential for

  6. Slide 6: Current IBD Targeted Therapy by Injectable Antibody

    Current IBD Targeted Therapy by Injectable Antibody A Growing Multi-Billion Dollar Market Drugs • Injectable Antibodies – Blockbuster drugs –Humira® & Remicade® for IBD; Global Humira ® 2016 sales ~ $ 16 B Low response rates –~30% non-responders; ~30% relapse rates (6-12 Mo’s) Safety concerns – blac

  7. Slide 7: Oral Targeted Therapy for IBD

    Oral Targeted Therapy for IBD Potential to Transform & Expand Current Treatment Paradigm • Potential advantages of oral, GI-restricted peptides PTG-100 & PTG-200 5-ASAs, Antibiotics Mild – – – – – Validated biological targets and/or pathways Reduced systemic infections Better safety & efficacy Bette

  8. Slide 8: PTG-100 α4β7 Antagonist for Inflammatory Bowel Disease

    PTG-100 α4β7 Antagonist for Inflammatory Bowel Disease 9

  9. Slide 9: PTG-100 Oral, α4β7-specific, GI-restricted, Targeted Therapy for IBD

    PTG-100 Oral, α4β7-specific, GI-restricted, Targeted Therapy for IBD • T cell homing regulated by interaction between α4β7 integrin and MAdCAM-1 MAdCAM-1 expressed only in intestinal vasculature Vedolizumab approved for Crohn’s & UC in 2014 • • • KOLs: α4β7-specific integrin blockers could potential

  10. Slide 10: Translating Preclinical PD & Efficacy Results to Clinical Studies

    Translating Preclinical PD & Efficacy Results to Clinical Studies Target Engagement Blood Surrogate PD readouts α4β7 antagonists Effect of PTG-100 1. 2. PTG-100 (oral peptide) vs. DATK32 (i.p. mAb) 1. 2. % receptor occupancy (RO) % receptor expression (RE) Human Efficacy PD Translation Clinical POC

  11. Slide 11: Established PD-based Clinical POC in Phase 1

    Established PD-based Clinical POC in Phase 1 Study 14 day MAD PD Data Guides Phase 2b Dose Range Placebo Cohort 5 300 mg 100 10 mg 75 0 50 -10 25 -20 0 -30 -25 g mg -50 -40 0 4 8 12 Time (h) 16 20 24 0 4 8 12 Time (h) 16 20 24 @24h CONFIDENTIAL 12 % receptor occupancy % Change from Baseline Translat

  12. Slide 12: PTG-100: Clinical Development Plans

    PTG-100: Clinical Development Plans Ph 2b Clinical POC/ analysis (Q1 2018) (Q4 2018) NHV (n=78) US Pre-AUS CTN US IND EFD = embryo-fetal development, PPN = pre-/post-natal development 13 201620172018 Q1Q2Q3Q4 Q1Q2Q3Q4 Q1Q2Q3Q4 CLINICAL DEVELOPMENT Ph 1-SAD/MAD/BAInterim futilityFinal analysis PD bas

  13. Slide 13: Phase 2b PROPEL Study in UC Patients

    Phase 2b PROPEL Study in UC Patients Randomized, Double-blind, Placebo-controlled Adaptive Parallel Design Stage 1 Stage 2 Primary endpoints: • Clinical remission • Safety & tolerability Placebo Placebo 150 mg QD Dose A Secondary Endpoints: 300 mg QD Dose B • • • • Clinical response Endoscopic respo

  14. Slide 14: PTG-100 Summary

    PTG-100 Summary • Oral peptide PTG-100 ✔ approach with validated target • Proof of target engagement & efficacy in rodent models of colitis Side by side comparison of PTG-100 vs. DATK32 (mouse  integrin mAb) Pre-Clinical ✔ • • • Blood receptor occupancy (%RO) Blood receptor expression (%RE) ✔ in

  15. Slide 15: PTG-200 Oral, IL-23 Receptor Specific, GI-restricted, Targeted Therapy for IBD

    PTG-200 Oral, IL-23 Receptor Specific, GI-restricted, Targeted Therapy for IBD Blocks IL-23 pathway p19 p35 p40 p40 Stelara® (IL-12/23, p40) approved for Psoriasis and CD, Phase 3 for UC Several IL-23 p19 antibodies in late-stage development for autoimmune indications (Risankizumab®, Brazikumab®) •

  16. Slide 16: Discovery of Oral IL-23 Receptor Antagonist PTG-200

    Discovery of Oral IL-23 Receptor Antagonist PTG-200 From Discovery to Pre-Clinical POC (1000+ peptides) to Ph1 Initiation Potency PK: Rats & Cynos ✓ Orally stable: fecal recovery in rats ✓ GI-restricted: <0.5% plasma exposure ✓ Principal exposure in various GI tissues PD & Efficacy • Efficacy in Col

  17. Slide 17: Protagonist & Janssen Collaboration

    Protagonist & Janssen Collaboration Development and Commercialization of PTG-200 1. Janssen is a world leader in IBD –mAbs franchise: Remicade®, Simponi®, Stelara® 2. Mutual excitement around oral targeted therapy drugs for IBD 3. Further validation for the ‘oral’ hypothesis –Stelara® is an injectab

  18. Slide 18: Janssen Collaboration for PTG-200

    Janssen Collaboration for Executed May 26, 2017 PTG-200 • Janssen receives exclusive WW license to PTG-200 • • • Phase 1: 100% Phase 2: 20% Phase 3 & beyond: 0% • • Janssen to lead WW commercialization PTGX has the right to co-detail up to 30% the US calls; gets reimbursed PTGX economics remains the

  19. Slide 19: Financials: Funding R&D efforts through 2019

    Financials Funding R&D efforts through 2019 21 •$104.9 M in cash, cash equivalents and investments at 3Q 2017 end – Includes $50 M up-front payment received in August 2017 from Janssen as part of PTG-200 licensing and collaboration agreement •$60 M follow-on offering in October 2017 – With the addit

  20. Slide 20: Protagonist Platform PTG-300 and Other Potential Future Applications

    Protagonist Platform PTG-300 and Other Potential Future Applications 22

  21. Slide 21: Peptide Technology Platform

    Peptide Technology Platform Potential for Broad Utility vs. Diverse Undruggable Targets Oral IL-23R antagonist Oral agonist GI non-IBD Oral α4β7 antagonist IL-6 antagonist Hepcidin mimetic Nav 1.7 blocker 23 Peptide Technology Platform

  22. Slide 22: PTG-300: Hepcidin Mimetic

    PTG-300: Hepcidin Mimetic Protagonist’s 3rd Asset in Clinical Development Hepcidin • • A natural hormone and master regulator of iron homeostasis Absence or deficiency of hepcidin associated with ineffective erythropoiesis and chronic anemia in iron-overload related rare diseases – β-thalassemia – M

  23. Slide 23: Hepcidin: Regulator of Iron Homeostasis

    Hepcidin: Regulator of Iron Homeostasis PTG-300 Hepcidin Mimetic Iron recycled by macrophages gets picked up by ferroportin; PTG-300 inhibits iron export to circulation Macrophage Hepcidin mimetic PTG-300 binds and degrades ferroportin; inhibiting iron export to circulation mimicking natural hepcidi

  24. Slide 24: PTG-300: Phase 1 Study in NHVs

    PTG-300: Phase 1 Study in NHVs PD Based Clinical Proof-of-Concept Established in Q4 2017 Cohort 1 1mg/ placebo Cohort 2 3 mg/ placebo Cohort 3 10 mg/ placebo Cohort 4 20 mg/ placebo • • SAD Cohorts 1-5 (1-40 mg) Cohort 5 40 mg/ placebo Cohort 6 80 mg/ placebo • • Cohort 6 - Higher dose (80 mg) Cohor

  25. Slide 25: PTG-300 Efficacy based POC in β-thalassemia Mouse Model

    PTG-300 Efficacy based POC in -thalassemia Mouse Model -thalassemic mouse model (Hbbth3+ Mice); 6 week treatment • • Evaluate effects on – Ineffective erythropoiesis – Iron overload • • PTG-300 1 mg/kg Q2D saline DFP (deferiprone, oral iron chelator) 1.25mg/mL water ad libitum Combination of PTG-3

  26. Slide 26: PTG-300: Improved Erythropoiesis

    PTG-300: Efficacy based POC in β-thalassemia Mouse Model Improved Erythropoiesis 12 11 10 9 8 7 6 5 17 16 15 14 13 12 11 10 9 8 *** **** ** **** ns * ** ns 50 40 30 20 10 0 60 ns 40 ns ** *** 20 0 29 Reticulocyte Percentage (%) RBC (x106 cells/L) Vehicle DFP PTG300 DFP + PTG300 HCT (%) HGB (g/dL) •

  27. Slide 27: PTG-300: Decreased Splenomegaly and Liver Iron Overload

    PTG-300: Efficacy based POC in β-thalassemia Mouse Model Decreased Splenomegaly and Liver Iron Overload 800 0.03 600 ns 0.02 400 * 0.01 ** 200 *** **** **** 0 0.00 30 Spleen/Body Weight (g/g) Total Liver Fe (ng /mg) wet tissue • PTG-300 1 mg/kg dosed Q2D for 6 weeks (Hbbth3+ Mice) • DFP (deferiprone

  28. Slide 28: PTG-300: Improved Erythropoiesis, Decreased Splenomegaly and Liver Iron

    PTG-300: Efficacy based POC in β-thalassemia Mouse Model Improved Erythropoiesis, Decreased Splenomegaly and Liver Iron • PTG-300 statistically improved erythropoiesis, decreased splenomegaly and liver iron overload DFP only decreased liver iron overload and did not statistically improve erythropoie

  29. Slide 29: PTG-300: Proposed Clinical Development Plan

    PTG-300: Proposed Clinical Development Plan • Single global phase 2/3 clinical trial in -thalassemia, MDS patients (basket protocol) Phase 2 dose-range finding – Open label single-arm study to identify safe and effective starting dose Phase 3 placebo-controlled pivotal trial – Randomized, double-bl

  30. Slide 30: Multiple Shots on Goal

    Multiple Shots on Goal Events & Milestones 2016-2018 (expected) - Ph 2b UC TLD (Q4) Ph 2 initiation - IND submission & Ph 2 - IND submission and *1 Initial indication to be pursued; each asset provides opportunities for multiple indications *2 We estimate current cash, including funds from the Janss

  31. Slide 31: Multiple Shots on Goal

    Multiple Shots on Goal Events & Milestones 2016-2018 2016 2017 20182 (expected) = Ph1 PD based clinical = Ph 2b UC interim (Q1) POC established (Q3) Ph 2b UC enrollment = Ph 2b UC TLD (Q4) - Ph 2b UC PROPEL continuation - Pouchitis FDA mtg and - initiation (Q4) Ph 2 initiation PTG-200 fs - Ph1TLD IL

  32. Slide 32: Protagonist Therapeutics

    Protagonist Therapeutics

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