PhaseRx, Inc. announced product pipeline advancements including the selection of its lead product candidate, PRX-OTC, for treatment of Ornithine Transcarbamylase Deficiency (OTCD) and positive proof-of-concept data for a second product candidate, PRX-ASL, for treatment of Argininosuccinate Lyase Deficiency (ASLD). OTCD and ASLD are urea cycle disorders (UCDs), a family of rare metabolic disorders that generally affect children. Each UCD is caused by an inherited single-gene deficiency that results in hyperammonemia (elevated ammonia in the blood), and can lead to irreversible neurological impairment, coma and death. Current treatments for these diseases focus on ameliorating effects of the disease, while the only curative option is liver transplant. PhaseRx is developing drugs to replace the missing or defective enzyme using intracellular enzyme replacement therapy (i-ERT), with the objective of reinstating function of the urea cycle. PhaseRx expects to generate Phase 2a (single-dose) and 2b (repeat-dose) clinical proof-of-concept data for PRX-OTC in 2018, including measurement of blood ammonia. This clinical development plan is supported by positive preclinical data showing that PRX-OTC normalized blood ammonia and resulted in 100% survival in the OTC-spfash mouse model. In this model, mice are defective in the same gene as humans with OTCD, and PRX-OTC replaced the human gene in the mouse. Preclinical studies in ASLD were conducted using ASL-deficient mice, which are defective in the same gene as humans with ASL deficiency. The new data with PRX-ASL therapy in the ASL-deficient mice showed statistically significant reduction in ammonia levels following two weeks of mRNA treatment.