Flagship-backed Rubius raises $120M to take off-the-shelf red blood cell cancer therapeutics into the clinic

Rubius President Torben Straight Nissen.

Rubius Therapeutics has raised $120 million to take two of its off-the-shelf red blood cell therapies into the clinic. The Flagship Pioneering-backed biotech is using its method for expressing proteins on allogeneic red blood cells to create candidates that hit multiple immuno-oncology targets.
Cambridge, Massachusetts-based Rubius’ pipeline is built on a way to create and weaponize red blood cells in large quantities in bioreactors, a manufacturing method it thinks gives it an edge over CAR-T drugs. The process generates enucleated red cells that express one or more protein either inside or on the surface the cell, depending on whether the goal is to treat a cancer or enzyme-related disease. 
This has enabled Rubius to equip individual red cells to deliver the types of one-two punches the big beasts of immuno-oncology are pursuing in their sea of combination trials.  
“We have been able to express both costimulatory molecules as well as other relevant proteins that are being used in immuno-oncology today on red cells. We don't need to combine those types of therapies because we can express them on red cells,” Rubius President Torben Straight Nissen, Ph.D. said. “We almost have a pipeline within one product.”
Nissen cites the combination of costimulatory molecules and checkpoint inhibitors as an example of the sorts of cocktails the red cells make possible. A red blood cell armed with this combination could simultaneously suppress a tumor’s ability to evade detection and fully activate T cells to dial up the immune system’s attack. Rubius is putting more than a million proteins on the surface of some of its cells in a bid to generate a strong interaction with other cells.
The potential for the approach to treat solid tumors and hematological cancers, plus its applications in diseases other than cancer, has enabled Rubius to raise $120 million from Flagship and large, undisclosed institutional investors.
Rubius will use the money to move two drugs into the clinic next year. The plan builds on work to generate preclinical proof-of-concept data on several programs. What indications the clinical-stage drugs will target remains a secret. But Nissen said Rubius is still interested in the phenylketonuria (PKU) enzyme-replacement program it talked up when it first emerged from the same Flagship incubator that spawned Moderna and Seres Therapeutics. 
The interest in using red cells as enzyme-replacement therapies stems from their ability to protect the payload from the immune system. Rubius thinks this will result in safe and effective therapies that persist in the body for months. 
At one stage Rubius planned to move the PKU program into the clinic in 2016. That plan was dropped as Rubius broadened the scope of its R&D activities—and took time out to create a scalable production process—after raising its first $25 million from Flagship in 2015. 
Back then, Rubius had created 50 different red cells. Today, the team has expressed 250 proteins on or in the red cells, opening doors beyond its initial focus on enzyme-replacement therapies such as the PKU program.
“As the company started to express more and more proteins on the surface of these red cells it became clear that the scope of the company was much broader than originally anticipated,” Nissen said.
The shift in Rubius’ perception of the therapeutic breadth of its platform has led it to look for deals. Nissen expects to enter into one or two strategic partnerships over the next 12 months. Rubius’ interest in the deals reflects the fact it lacks the bandwidth to simultaneously seize all the opportunities presented by the platform.  
To date, Rubius is yet to encounter any limitations in the types of proteins it can make the cells express. Nissen thinks there must be an upper limit in terms of protein size and probably a ceiling on the number of different proteins that can be expressed, too. But Rubius is yet to hit either level in its experiments so far.
Attention will shift away from these ongoing experiments over the coming 12 months as Rubius grows into a clinical-phase biotech. Headcount is set to grow from 40 to 100.
The new hires will help Rubius get into the clinic and beyond. Nissen thinks the funding will equip Rubius to take its lead programs to “clinical proof of concept, maybe even beyond that.” The uncertainty stems from the potential for data to open up opportunities to move forward faster, for example if the enzyme-replacement therapy snags breakthrough status and powers into a pivotal trial.