Treating sick people with healthy blood is nothing new. But a new biotech company wants to treat disease by transforming red blood cells into tiny medicine delivery pods, using genetic engineering techniques that have helped turn other human cells into cutting-edge cancer therapies.
The startup is called Rubius Therapeutics, and it’s announcing today a $25 million investment from Flagship Ventures, a Cambridge, MA-based venture group.
Rubius is starting with donated human hematopoetic stem cells, the type that turn into red blood cells in the bone marrow. By adding genetic material to the DNA of those stem cells and bathing them in other substances—some of which Rubius CEO Avak Kahvejian calls “our trade secret”—Rubius aims to produce red blood cells that carry a therapeutic payload and can be transferred into patients.
Meanwhile, Rubius has been working behind the scenes, although not entirely, having been name-checked as recently as October in this GenomeWeb story about a Boston research lab that figured out a way to produce the cells more affordably.
Rubius has combined work licensed from academic labs and its own in-house research to create 50 kinds of new cells, with its first tests in humans coming next year, says CEO Avak Kahvejian (pictured). Its most advanced program is for the rare disorder phenylketonuria, or PKU, a dangerous build-up in the body of the amino acid phenylalanine.
One immediate question about the science behind Rubius is whether engineered red blood cells, derived from someone else’s bone marrow, would set off immune system alarms, and potentially dangerous reactions, in the recipients. Kahvejian says it’s unlikely for a simple reason: The blood type O-negative is universal. Rubius would only work with O-negative cells.
“With every medicine there are questions of immunogenicity,” says Kahvejian, referring to an unwanted provocation of the immune system. “I would never say never, but compared to other biotherapeutics or cell therapeutics, red blood cells would be of the least concern” in causing an immune reaction.
Fears of immune reaction or rejection are one reason most of the cutting-edge T cell cancer therapies making their way through the clinic use autologous T cells—those harvested from a patient, modified in a lab, then re-infused back into the patient. It’s a personalized but cumbersome process, which is why allogeneic cell therapies, in which donated cells from one person are genetically modified to blunt a possible immune “mismatch” so they can potentially treat a range of patients, are also intriguing.
Rubius wants to go the allogeneic route with its red blood cells. For PKU, the therapeutic cells will be engineered to produce and carry around an enyzme that breaks down phenylalanine. People with PKU lack the enzyme phenylalanine hydroxylase, but Kahvejian declined to say whether that was the enzyme Rubius aims to reproduce. “That’s only one of our options for processing phenylalanine,” he says.
In people with PKU, phenylalanine builds up in the bloodstream with dangerous side effects, including brain damage. Those diagnosed with the mutation must eat diets low in protein to avoid producing too much of the amino acid.
In Rubius’s tests, conducted with human blood but outside the body, the cells modified to contain the enzyme manage to break down enough phenylalanine to give the company hope of having a therapeutic effect in people.
To engineer the cells, Rubius is using modified viruses to shoot new genetic material into their DNA. When asked if Rubius has considered using CRISPR-Cas9, the gene editing system that has spread like wildfire through research labs across the world, Kahvejian says the method Rubius is using—lentiviral transduction—“is a well-accepted way to get stuff into cells,” such as the modified T cells used in CAR-T therapies. “CRISPR is a way to get stuff out of cells.”
For all the fascination and work around CRISPR, its ability to stitch new genetic material into DNA is not well developed. The system has advanced farther as a way to snip out unwanted genetic material, as Kahvejian notes, but even then, a CRISPR-modified product has yet to be tested in people.
Kahvejian is part of the VentureLabs group within Flagship that cooks up new companies. Other VentureLabs companies besides Rubius include Moderna Therapeutics, Pronutria, and Seres Therapeutics.
Kahvejian says he wants Rubius to expand its blood cell concept to produce therapies in several disease areas. That would follow the ambitions of Moderna, which has taken a novel idea for therapeutics—spurring a patient’s own cells to become mini drug factories by injecting them with bits of RNA—and cleaved off several product ideas.
Moderna has raised almost a billion dollars through financings and partnership deals, and created wholly owned subsidiaries each with a different focus: cancer, infectious disease, rare diseases, and cancer vaccines.
When asked if Rubius plans to follow the Moderna model, Kahvejian has a one-word answer: “Maybe.”
The firm’s board of directors is comprised of Flagship CEO Noubar Afeyan; the Whitehead Institute’s Harvey Lodish, whose lab has done some of the work on Rubius’s system to produce engineered red blood cells; investor Jim Gilbert, formerly of Bain & Co. and the Rubius chairman; MIT professor Bob Langer; Seres Health CEO Roger Pomerantz; Merck chief medical officer Michael Rosenblatt; and Covington & Burling senior counsel Peter Hutt.