Slide 1: Unlocking the value of mRNA - Investor Presentation July 2017
Unlocking the value of mRNA™ ® INVESTOR PRESENTATION JULY 2017 NASDAQ: PZRX Issuer Free Writing Prospectus Filed Pursuant to Rule 433 of the Securities Act of 1933, as amended Registration Statement No. 333 - 218872
Slide 2: Forward-Looking Statements
.. FORWARD - LOOKING STATEMENTS This presentation contains forward - looking statements which are based on current expectations, estimates and projections. Statements that are not historical facts are forward - looking statements and typically are identified by words like “may”, “believe”, “anticipa
Slide 3: Free Writing Prospectus
.. FREE WRITING PROSPECTUS This presentation highlights basic information about PhaseRx , Inc. and the offering. PhaseRx , Inc. has filed a registration statement on Form S - 1 (Registration No. 333 - 218872) (including a prospectus) with the U.S. Securities and Exchange Commission (the “SEC”) for t
Slide 4: Contents
.. CONTENTS • Investment Summary • Unmet Medical Need and Our Solution • PRX - OTC Development • Market Opportunity • Platform and Corporate Development • Corporate Information • Backup Slides 4
Slide 5: Investment Summary
.. INVESTMENT SUMMARY - NASDAQ:PZRX • mRNA drugs for life - threatening inherited liver diseases in children • C linical POC with an approvable endpoint expected next year 5 Focus • Enzyme replacement therapy, or ERT ( Genzyme/ BioMarin ) that is effective inside the diseased cell: i - ERT • Proprie
Slide 6: Unmet Medical Need and Our Solution
.. UNMET MEDICAL NEED AND OUR SOLUTION 6
Slide 7: OTCD Is a Significant Market Opportunity
.. OTCD IS A SIGNIFICANT MARKET OPPORTUNITY • Ornithine Transcarbamylase Deficiency (OTCD) causes high blood ammonia that can result in to cumulative and permanent brain damage, coma and death • Current ammonia scavenger therapy (e.g., Ravicti ) does not correct the disease – patients still have cri
Slide 8: PRX-OTC Has a Compelling Value Proposition
.. PRX - OTC HAS A COMPELLING VALUE PROPOSITION 8 PRX - OTC GOAL ( Enzyme Replacement ) RAVICTI ( Ammonia Scavenger ) Target Patients • OTCD patients from birth • OTCD patients > 2 mo Dosing • W eekly or every other weekly IV infusion • Oral: three times daily Mechanism • Replace OTC enzyme to corre
Slide 9: UCDs Cause Cumulative, Permanent Brain Damage
.. UCD s CAUSE CUMULATIVE, PERMANENT BRAIN DAMAGE 9 • Single gene defects resulting in inability to metabolize ammonia • High blood ammonia leads to cumulative and permanent brain damage, coma and death • Liver transplant is the only corrective therapy • The only available drug treatment is the ammo
Slide 10: Hybrid mRNA Technology
.. F ormulation administered by infusion Polymer mediates mRNA delivery into cell HYBRID m RNA TECHNOLOGY™ 10 Hybrid mRNA Technology GalNAc - Targeted Polymer Provides Delivery to Cytoplasm Inert LNP Provides mRNA Protection and Delivery to Liver Hybrid mRNA Technology ™: Highly Effective mRNA Deliv
Slide 11: PRX-OTC Makes Abundant OTC Enzyme
.. PRX - OTC MAKES ABUNDANT OTC ENZYME 11 • PRX - OTC makes OTC protein out to ≥ day 10 post - dose by Western blot • PRX - OTC treatment results in a ≈ 100 % increase in OTC enzyme activity at day 10 post - dose Treatment With PRX - OTC Results in High Levels of OTC Enzyme for >10 days in Normal Mi
Slide 12: PRX-OTC Fully Corrects Disease in OTCD Mice
.. PRX - OTC FULLY CORRECTS DISEASE IN OTCD MICE 12 • PRX - OTC normalizes blood ammonia levels in OTC spf - ash OTCD mice • PRX - OTC completely rescues mice from toxic effects of ammonia: 100% survival PRX - OTC Treatment Normalizes Blood Ammonia and Rescues 100 % of Mice in Well - Accepted Mouse
Slide 13: Formulation Well-Tolerated in Multiple Species
.. FORMULATION WELL - TOLERATED IN MULTIPLE SPECIES 13 Rats Non - Human Primates No Statistically Significant Dose - Dependent Increases in Liver Function Tests (LFTs) or Cytokines in Rats or Non - Human Primates LFTs Cytokines Buffer 1 mg/kg 3 mg/kg 5 mg/kg 0 50 100 150 200 A L T ( U / L ) Buffer 1
Slide 14: PRX-OTC Expected to Show Clinical POC in 2018
.. PRX - OTC EXPECTED TO SHOW CLINICAL POC IN 2018 14 PROGRAM LEAD OPTIMIZATION PRECLINICAL IND - ENABLING PHASE 2a/2b PHASE 3 PRX - OTC Ornithine Transcarbamylase Deficiency PRX - ASL Argininosuccinate Lyase Deficiency PRX - ASS1 Argininosuccinate Synthase 1 Deficiency IND Filing Expected 2018 Data
Slide 15: PRX-OTC Development
PRX-OTC DEVELOPMENT © PhaseRx’
Slide 16: PRX-OTC Development Is on Track
.. PRX - OTC DEVELOPMENT IS ON TRACK • Successful pre - IND meeting (FDA) and scientific advice process (EMA) • Orphan drug status has been granted in the U.S. and EU • Substantial progress made with CMOs to scale up manufacture of PRX - OTC • Dose range finding studies – Planned for 1H 2018 • IND e
Slide 17: Single 2a/2b Trial Design Has Fast Endpoints
.. SINGLE 2 a / b TRIAL DESIGN HAS FAST ENDPOINTS 17 Phase 2a • Single Dose • Adult and Pediatric OTCD Patients • Multi - Center at UCDC sites • ~12 patients • Safety • Blood ammonia (24h) • Ureagenesis (2h) OTCD Patients On Scavenger >2 years old 0.1 mg/kg mRNA 0.3 mg/kg mRNA 1.0 mg/kg mRNA ~12 Pat
Slide 18: Market Opportunity
MARKET OPPORTUNITY PhaseRx’
Slide 19: UCD Market Is Analogous to the Existing ERT Market
.. UCD MARKET IS ANALOGOUS TO THE EXISTING ERT MARKET 19 UCD i - ERT market opportunity is completely untapped… DISEASE INCIDENCE DRUG COMPANY STATUS OTC Deficiency 1/56,500 PRX - OTC PhaseRx Pre - commercial ASL Deficiency 1/218,750 PRX - ASL PhaseRx Pre - commercial ASS1 Deficiency 1/250,000 PRX -
Slide 20: Expensive Scavengers Do Not Correct the UCDs
.. EXPENSIVE SCAVENGERS DO NOT CORRECT THE UCD s 40 LARGE TABLETS per day, bad odor Oral liquid 3x per day IV scavenger given in ICU/PICU 20 1 Berry et al 2014 Mol Genet Metab. 112(1): 17 - 24 2 Lee et al 2010 Mol Genet Metab. 100(3): 221 - 8 3 https://endpts.com/the - new - top - 10 - most - expens
Slide 21: OTCD Is a Significant Market Opportunity
.. OTCD IS A SIGNIFICANT MARKET OPPORTUNITY • Ornithine Transcarbamylase Deficiency (OTCD) causes high blood ammonia that can result in to cumulative and permanent brain damage, coma and death • Current ammonia scavenger therapy (e.g., Ravicti ) does not correct the disease – patients still have cri
Slide 22: Platform and Corporate Development
.. PLATFORM AND CORPORATE DEVELOPMENT 22
Slide 23: PRX-ASL: Second POC in Preclinical Disease Model
.. PRX - ASL: SECOND POC IN PRECLINICAL DISEASE MODEL • ASL deficiency (ASLD) is an autosomal recessive inherited disease causing elevated blood ammonia • Lowering of blood ammonia is also believed to be an approvable endpoint for ASL deficiency • PRX - ASL – S ame Hybrid mRNA Technology – ASL mRNA
Slide 24: Validated Platform Drives Product Opportunities
.. VALIDATED PLATFORM DRIVES PRODUCT OPPORTUNITIES 24 Hybrid mRNA Platform Validation Future Product Opportunities i - ERT Products to Treat: • Organic Acidemias • Glycogen Storage Diseases • Porphyria • Hyperoxalurea • Phenylketonuria • Tyrosinemia • Wilson’s Disease In Vivo Gene Editing: Strong be
Slide 25: Platform Fuels Partnering Opportunities
.. PLATFORM FUELS PARTNERING OPPORTUNITIES 25 Therapeutic Focus • Rare diseases • Patients failed by existing treatments Value to Partners • Correct physiology of devastating diseases • Specific activity in liver and avoiding off - target effects • High levels of expression and activity • Achieving
Slide 26: Products Have Strong Patent Protection
.. PRODUCTS HAVE STRONG PATENT PROTECTION 26 • Initial IP exclusively licensed from the University of Washington and developed internally – Portfolio covers all the world's major pharmaceutical markets – 43 patents issued and over 15 applications pending worldwide PRX - OTC is protected by: • Dibloc
Slide 27: Competitive Landscape
.. COMPETITIVE LANDSCAPE mRNA • Most mRNA companies are focused on mRNA vaccines, where there is a much lower delivery hurdle • PhaseRx’s success is founded on a world - class team – Deep domain experience in the delivery of nucleic acid therapeutics • We believe Hybrid mRNA Technology has superior
Slide 28: Corporate Information
.. CORPORATE INFORMATION 28
Slide 29: Financial Highlights
.. FINANCIAL HIGHLIGHTS 29 1 Based on 10 - Q filing for quarter ended March 31, 2017. PhaseRx , Inc. Exchange / Ticker NASDAQ / PZRX Shares outstanding 11.69 M 1 Market cap ~$ 12M Major institutiona l holders Arch Venture Partners, Versant Ventures, 5AM Ventures Key financials $11.9M cash 1 Institut
Slide 30: Top-Tier Team with Deep Domain Experience
.. TOP - TIER TEAM WITH DEEP DOMAIN EXPERIENCE 30 MANAGEMENT Robert Overell, Ph.D. President and CEO Michael Houston, Ph.D . Chief Scientific Officer Gordon Brandt, M.D . Chief Medical Officer Helen Tsui, CPA SVP, Principal Accounting Officer Spencer Lemons Head of Business Development Mary Prieve,
Slide 31: Near-Term Potential Milestones
.. NEAR - TERM POTENTIAL MILESTONES 31 EVENT ANTICIPATED TIMING POC in Second Disease Model 2Q 2016 – Achieved Declare Lead Development Candidate 2Q 2016 - Achieved Large Animal Tolerability Study 4Q 2016 - Achieved U.S. Orphan Drug Designation – PRX - OTC 4Q 2016 - Achieved E.U. Orphan Drug Designa
Slide 32: Investment Summary
.. INVESTMENT SUMMARY - NASDAQ:PZRX • mRNA drugs for life - threatening inherited liver diseases in children • C linical POC with an approvable endpoint expected next year 32 Focus • Model: Enzyme replacement therapy, or ERT ( Genzyme/ BioMarin ) • Intracellular ERT, or i - ERT: effective inside the
Slide 33: Investor Contact
Unlocking the value of mRNA™ ® Investor Contact: Robert W. Overell, President and CEO robert@phaserx.com
Slide 34: Backup Slides
BACKUP SLIDES © PhaseRx’
Slide 35: Safety Study in Non-Human Primates
.. SAFETY STUDY IN NON - HUMAN PRIMATES • Study Design – Single - dose study in cynomolgus monkeys (N=3/group) – Hybrid mRNA Technology formulated with human EPO (hEPO) mRNA – Endpoints: safety and EPO expression • Results – Dose responsive increase in blood EPO levels from 0.1 to 1 mg/kg mRNA – No
Slide 36: PRX-OTC: Phase 2a/2b Clinical Development
.. PRX - OTC: PHASE 2 a /2 b CLINICAL DEVELOPMENT • Phase 2a: Administer single dose on Day 1. Observe safety and measure duration and degree of urea production and ammonia reduction. • Phase 2b: 4 weekly doses at the optimal biological dose . Observe safety and measure duration and degree of urea p
Slide 37: OTC Deficiency – Diagnosis and Progression
.. OTC DEFICIENCY – DIAGNOSIS AND PROGRESSION • Ornithine transcarbamylase deficiency (OTCD) - 1/56,500 incidence, no ethnicity or geography spared • Awareness, diagnosis and survival rates expected to improve if corrective therapy available • Presents as a calamity at birth with vomiting, followed