Slide 1: Unlocking the value of mRNA
Unlocking the value of mRNA ® CORPORATE PRESENTATION March 8, 2017 NASDAQ: PZRX
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: Investment Summary
.. INVESTMENT SUMMARY 3 Strategy Team Pipeline Partnering • Broad nucleic acid experience with proven track record • Three urea cycle disorder (UCD) programs in development • Preclinical reduction in blood ammonia shown in two programs (FDA approvable endpoint for the UCDs) • Significant partnering
Slide 4: Market Opportunity
.. MARKET OPPORTUNITY 4 i - ERT market opportunity for UCDs is completely untapped… DISEASE INCIDENCE DRUG COMPANY 2015 SALES 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 - ASS1 PhaseRx Pre - comm
Slide 5: PhaseRx Hybrid mRNA Technology Platform
.. PHASERX HYBRID MRNA TECHNOLOGY™ PLATFORM 5 Advantages of Hybrid mRNA Technology: • Targets synthesis to hepatocytes • Improved tolerability • High levels of expression and activity • Enables repeat dosing regimens Polymer Nanoparticle Inert Lipid Nanoparticle GalNAc - Targeted Polymer Provides De
Slide 6: Development Pipeline
.. DEVELOPMENT PIPELINE 6 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 First IND planned for 4Q 2017 - Clinical POC expected in
Slide 7: UCDs: Progressive and Permanent Brain Damage
.. UCDS: PROGRESSIVE AND PERMANENT BRAIN DAMAGE 7 • UCDs: a family of metabolic disorders with devastating patient consequences • Each results from an inherited single - gene deficiency • Hyperammonemia causes cumulative and permanent brain damage, coma and death • Liver transplant is the only curre
Slide 8: OTC Deficiency – Diagnosis and Progression
.. OTC DEFICIENCY – DIAGNOSIS AND PROGRESSION 8 • 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, followe
Slide 9: OTC Deficiency – Current Therapy Fails Patients
.. OTC DEFICIENCY – CURRENT THERAPY FAILS PATIENTS • Current disease management requires ammonia scavengers and adherence to protein restricted, unpalatable diet – Hyperammonemic crises still occur • Even under the controlled conditions of a clinical trial, ammonia scavengers don’t do the job: • 25%
Slide 10: PRX-OTC: Value Proposition vs Ravicti
.. PRX - OTC: VALUE PROPOSITION VS RAVICTI 10 RAVICTI PRX - OTC GOAL Target Patients • OTCD patients > 2 yo • OTCD patients from birth Efficacy • Palliative care of symptoms • Hyperammonemic crises still occur • Replace OTC protein to correct the disease • Normalize plasma ammonia levels Dosing & Ad
Slide 11: Human OTC Levels in CD1 Mice
.. HUMAN OTC LEVELS IN CD1 MICE • Study Design: – CD1 mice were treated with a single dose of OTC mRNA – Livers collected at endpoints were examined by western analysis and for OTC enzyme activity • Results: – High levels of protein expression by Western blot analysis – Duration of OTC expression is
Slide 12: PRX-OTC Efficacy: Reduction in Toxic Ammonia
.. 0 50 100 150 200 250 300 350 Buffer OTC mRNA Normal Mice Hyperammonemia Induced spf-ash Mice Plasma Ammonia (µM) Day 14 Day 21 PRX - OTC EFFICACY: REDUCTION IN TOXIC AMMONIA 12 • Hyperammonemia can be induced in OTC - spf ash mice • Hyperammonemia is the hallmark of human OTCD and causes CNS dama
Slide 13: PRX-OTC Efficacy: Survival
.. 0 5 10 15 20 25 30 35 0 20 40 60 80 100 Buffer OTC mRNA Days Post Induction of Hyperammonemia % S u r v i v a l Control mRNA PRX - OTC EFFICACY: SURVIVAL • Treatment with PRX - OTC results in complete survival of hyperammonemia induced OTC - spf ash mice • All mice succumbed to hyperammonemia in
Slide 14: Non-Human Primate Safety Study
.. NON - HUMAN PRIMATE SAFETY STUDY • 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 no
Slide 15: PRX-OTC: Development Plan
.. PRX - OTC: DEVELOPMENT PLAN • Working with CMOs to scale up and manufacture PRX - OTC • Dose range finding studies – Planned for Q2 2017 • IND enabling GLP toxicology – Planned for H2 2017 • IND filing – Planned submission Q4 2017 • Clinical trial expected to begin patient enrollment in H1 2018 –
Slide 16: ASL Deficiency: Diagnosis and Progression
.. ASL DEFICIENCY: DIAGNOSIS AND PROGRESSION • ASL deficiency (ASLD) leads to argininosuccinic aciduria, an autosomal recessive inherited disease causing: – elevated blood ammonia – accumulation of argininosuccinic acid (ASA) in blood and urine – developmental delay and retardation – effects on live
Slide 17: PRX-ASL Reduces Toxic Ammonia Levels
.. PRX - ASL REDUCES TOXIC AMMONIA LEVELS • ASL - deficient mice are very sick, small in size and have elevated ammonia levels • They die due to multi - organ failure over a range from a few weeks to 3 - 4 months • Mice are put on triple therapy at birth to help extend life span (sodium benzoate, L
Slide 18: mRNA Therapeutic Product Generator
.. MRNA THERAPEUTIC PRODUCT GENERATOR 18 Ability to rapidly manufacture new mRNAs Known sequences of all mRNAs Proprietary PhaseRx Hybrid mRNA Technology i - ERT Products to Treat: • Organic Acidemias • Glycogen Storage Diseases • Porphyria • Hyperoxalurea • Urea Cycle Disorders • Phenylketonuria •
Slide 19: Partnering Opportunities
.. PARTNERING OPPORTUNITIES 19 Therapeutic Focus • Rare diseases • Patients failed by existing treatments Value to Partners • Correct physiology of devastating diseases • In vivo instead of ex vivo delivery • Specific activity in liver and avoiding off - target effects • High levels of expression an
Slide 20: Expanding Intellectual Property
.. EXPANDING INTELLECTUAL PROPERTY • Initial IP exclusively licensed from the University of Washington and developed internally – Portfolio covers all the world's major pharmaceutical markets – Over 30 patents issued and over 35 applications pending worldwide • Diblock Polymer family – Issued in 6 t
Slide 21: Management Team: Broad Nucleic Acid Experience
.. MANAGEMENT TEAM: BROAD NUCLEIC ACID EXPERIENCE 21 • Robert Overell, Ph.D., President and Chief Executive Officer Frazier Healthcare Ventures, Targeted Genetics, Immunex • Michael Houston, Ph.D., Chief Scientific Officer Nastech /MDRNA • Gordon Brandt, M.D., Chief Medical Officer Nastech /MDRNA •
Slide 22: Board of Directors
.. BOARD OF DIRECTORS • Steven Gillis, Ph.D., Chairman Managing Director, ARCH Venture Partners • Brian Atwood Managing Director, Versant Ventures • Michelle Griffin Former Corixa , Trubion CFO/COO • Paul Johnson, Ph.D. Cofounder and former CSO • Robert Overell, Ph.D. President and CEO • Peggy Phill
Slide 23: Financial Highlights
.. FINANCIAL HIGHLIGHTS 23 1 Based on 10 - Q filing for quarter ended September 30, 2016. PhaseRx , Inc. Exchange / Ticker NASDAQ / PZRX Shares outstanding 11.69 M 1 Market cap ~$20M Major institutiona l holders Arch Venture Partners, Versant Ventures, 5AM Ventures, Fidelity Key Financials $18.6M ca
Slide 24: Near-Term Potential Milestones
.. NEAR - TERM POTENTIAL MILESTONES 24 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 GMP Manufacturing 3Q 2017 File IND 4Q 2017 Phase 2a Single - dose Safety and Efficac
Slide 25: Investment Summary
.. INVESTMENT SUMMARY 25 Strategy Team Pipeline Partnering • Broad nucleic acid experience with proven track record • Three urea cycle disorder (UCD) programs in development • Preclinical reduction in blood ammonia shown in two programs (FDA approvable endpoint for the UCDs) • Significant partnering
Slide 26: Investor Contact
Unlocking the value of mRNA ® Investor Contact: Erin S. Cox, Director of Investor Relations erin@phaserx.com