As it gets ready to bring the first engineered red blood cell therapy into the clinic, Rubius Therapeutics Inc. is working up the next generation of RBC therapies to mimic immune cell interactions. The company is exploiting the cells’ unique biology to expand its pipeline beyond enzyme replacement into cancer and autoimmunity.
Rubius’ strategy is to engineer immune responses by putting the right combination of antigens, cytokines or costimulatory molecules on RBC surfaces. The idea is that when embedded in RBC membranes, these proteins will form high avidity interactions with receptors on immune cell surfaces.
“By expressing hundreds of thousands of copies of those agonists in the right conformation on the surface of the cell, we create these cell-cell interactions, mimicking and amplifying the way the immune system works,” said CEO Pablo Cagnoni.
Rubius’ Red Cell Therapeutics platform brings a new set of features to the cellular immunotherapy repertoire. Its cells stay in the circulation, which cuts down toxicity risk in immuno-oncology, and are cleared by a tolerizing pathway in the liver that can be harnessed to treat autoimmunity.
The company’s central thesis is that the longevity of mature RBCs in vivo, and their lack of replication, protein synthesis and protein degradation, allow them to deliver long-lasting, controlled doses of therapeutic proteins (see “Notorious RBC”).
The Flagship Pioneering-backed company, which emerged from stealth in 2015, will put its platform to the test this year in a Phase Ib/IIa trial of RTX-134 for phenylketonuria (PKU). Rubius plans to submit an IND in 1Q19.
RTX-134 is an enzyme replacement therapy comprised of donor-derived RBCs whose cytoplasms are loaded with a bacterial enzyme that breaks down phenylalanine.
“We create these cell-cell interactions, mimicking and amplifying the way the immune system works.” – Pablo Cagnoni, Rubius Therapeutics