Phaserx Inc · OTC:PZRXQ
Phaserx — 5th International mRNA Conference 2017
14 slides from Phaserx's conference presentation, Oct 31, 2017
Slide 1: mRNA Therapeutics for Urea Cycle Disorders
Unlocking the value of mRNA ® m RNA THERAPEUTICS FOR UREA CYCLE DISORDERS 5 th International mRNA Conference November 1 - 2, 2017, Berlin Robert W. Overell, Ph.D. President and CEO
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: UCDs Cause Cumulative, Permanent Brain Damage
.. UCD s CAUSE CUMULATIVE, PERMANENT BRAIN DAMAGE 3 • 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 4: Hybrid mRNA Technology
.. Formulation administered by infusion Polymer mediates mRNA delivery into cell HYBRID m RNA TECHNOLOGY™ 4 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 Delivery
Slide 5: Luciferase Expression at 6 h Post-Dose
.. LUCIFERASE EXPRESSION AT 6 H POST - DOSE 1 mg/kg 3 mg/kg 10 mg/kg PF0112/PRX847 formulation with luciferase mRNA led to dose responsive protein production up to 10 mg/kg. 5
Slide 6: Tissue-Specific Expression with GalNAc Targeting
.. TISSUE - SPECIFIC EXPRESSION WITH G al NA c TARGETING GalNAc targeting results in specific expression in liver • No expression observed in spleen, lymph nodes, kidney, lungs, or other tissues Ex Vivo Luciferase Analysis of CD1 Mouse Tissues Spleen Liver Kidney Lung Heart Pancreas Uterus/Ovaries 6
Slide 7: PRX-OTC Makes Abundant OTC Enzyme
.. PRX - OTC MAKES ABUNDANT OTC ENZYME 7 • 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 Mice
Slide 8: PRX-OTC Fully Corrects Disease in OTCD Mice
.. PRX - OTC FULLY CORRECTS DISEASE IN OTCD MICE 8 • 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 Mo
Slide 9: Repeat Dosing in Rats: OTC Expression
.. PRX - OTC REPEAT DOSING IN RATS: OTC EXPRESSION 9 9.0 2.3 4.3 0 2 4 6 8 10 Normal Human Liver 1 dose 3 doses ng hOTC/ug total protein hOTC Protein Level in Rat Liver 48 h post Final Dose • In a weekly repeat dose study in rats, we have seen the predicted accumulation of OTC protein – Week 3 prote
Slide 10: Repeat Dosing in Rats: Liver Enzymes
.. PRX - OTC REPEAT DOSING IN RATS: LIVER ENZYMES 10 Dose 1 Dose 1 Dose 3 0 100 200 300 P631: Serum ALT at 24 h Post-Dose A L T ( U / L ) 3X ULN 3 mg/kg OTC mRNABuffer Dose 1 Dose 1 Dose 3 0 100 200 300 400 500 P631: Serum AST at 24 h Post-Dose A S T ( U / L ) 3X ULN 3 mg/kg OTC mRNABuffer • After 3
Slide 11: Repeat Dosing in Rats: Cytokines
.. PRX - OTC REPEAT DOSING IN RATS: CYTOKINES 11 • After 3 weekly repeat doses of 3 mg/kg OTC mRNA, no changes in cytokines 0 2 4 6 8 10 GM-CSF IFN - γ IL-12p70 IL-6 TNF - α MCP-1 Fold Chnage to Buffer 6 h Post - Dose PRX - OTC Buffer m059 1 Dose m059 3 Doses 0 2 4 6 8 10 GM-CSF IFN - γ IL-12p70 IL-
Slide 12: Expected to Show Clinical POC in 2018
.. PRX - OTC EXPECTED TO SHOW CLINICAL POC IN 2018 12 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 13: Single 2a/2b Trial Design Has Rapid Endpoints
.. SINGLE 2 a / b TRIAL DESIGN HAS RAPID ENDPOINTS 13 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 Pa
Slide 14: PhaseRx Team
.. P hase R x TEAM Chemistry: • Sean Monahan, Ph.D. • Debashish Roy, Ph.D. • Anna Galperin, Ph.D. • Jean - Rene Ella - Menye, Ph.D. • Matt Waldheim, MSc. Biology: • Mary Prieve, Ph.D. • Allen Li, M.D., Ph.D. • Pierrot Harvie, Ph.D. • Amber Paschal, MSc. • Teri Blevins, B.S.,LAT • Eric Bell, B.S., LA