Rubius Therapeutics, Inc. announced anticipated 2019 milestones and operational updates: Rare Enzyme Deficiency Disorders Overview: Red Cell Therapeutics (RCTs) are engineered to express therapeutic enzymes within the cell and to shield those enzymes from the immune system. In rare enzyme deficiencies, RCTs are designed to circulate in the blood stream and degrade toxic metabolites that accumulate as a result of these deficiencies. Compared to current therapeutic approaches, RCT product candidates may have a more sustained treatment effect given the 120-day circulating time of red blood cells and may have a lower incidence of immune-driven adverse events, including the formation of neutralizing antibodies to the therapeutic enzyme, which often results in a reduction in efficacy. RTX-134 for the Treatment of Phenylketonuria (PKU): RTX-134 is genetically engineered to express the enzyme phenylalanine ammonia lyase (PAL) inside the RCT to convert phenylalanine into two metabolites, trans-cinnamic acid and ammonia. RTX-134 is designed to treat PKU, a rare disease characterized by a buildup of the neurotoxic amino acid phenylalanine. IND filing on track for first quarter of 2019. Initial data expected in 2H’19 from Part 1 of the RTX-134 Phase 1b/2a clinical trial in adults with PKU. High-level objectives for the RTX-134 clinical trial: Part 1: Single-dose administration. Preliminary safety. Longevity of cells in circulation. Production of trans-cinnamic acid as a biomarker of RTX-134’s mechanism of action. Dose and schedule selection for Part 2 of the study. Part 2: Multi-dose administration. Safety Efficacy Magnitude of reduction in phenylalanine. Dose and schedule optimization. RCT product candidates can be engineered to express combinations of co-stimulatory molecules on the cell surface to directly engage T and NK cells to activate the adaptive and innate immune systems. The goal is to stimulate these immune cells to proliferate, activate, migrate and, ultimately, to attack and kill tumors. RTX-240 (formerly RTX-212) for the Treatment of Solid Tumors: RTX-240 co-expresses 4-1BBL and IL-15TP, a fusion of IL-15 and IL-15 receptor alpha, with the goal of improving anti-tumor activity and overcoming resistance to immunotherapy in patients with solid tumors. IND filing expected by early 2020. Preclinical data is expected to be presented or published during 2019. RTX-224 for the Treatment of Solid Tumors. RTX-224 co-expresses 4-1BBL and IL-12 on the cell surface with the goal of improving overall anti-tumor immune response. In preclinical models, RTX-224 drives deep tumor regressions and improved safety. Preclinical data is expected to be presented or published during 2019.