Jonathan Wosen Freelance Writer GEN
New Red-Blood-Cell-Derived Therapies Are Poised to Launch Rubius into the Spotlight.
David Epstein has spent nearly 30 years in the pharmaceutical industry — first as the head of Novartis Oncology, which he helped grow into the world’s second largest cancer company, and then as the head of Novartis Pharmaceuticals. Along the way, he realized that great ideas can come from unlikely places.
“You think companies build these big strategic plans—they know exactly what they want to do and that’s how they end up in a certain space—but the reality often is quite different,” said Epstein.
While head of Novartis Pharmaceuticals, Epstein did what countless others do every day—he went onto the New York Times’ website to read the news. One article in particular caught his attention. It described a way to take a person’s T cells— immune cells that recognize molecules on the surface of infected or cancer cells—and modify them to target tumors. These altered cells, known as chimeric antigen receptor T cells (CAR-T), could then be administered back into the patient to destroy the tumor cells.
Epstein was excited by the potential of using the immune system to fight cancer, and reached out to Dr. Carl June—the University of Pennsylvania professor behind the CAR-T work.
“In this article, it looked like [June] had almost cured [chronic lymphocytic leukemia] … We were not thinking about cell therapy at all at that time,” said Epstein. “It seemed a little bit crazy; it seemed a little too good to be true.”
In 2012, the University of Pennsylvania and Novartis announced a major partnership, in which Penn granted Novartis exclusive rights to its CAR-T therapies. In return, Novartis gave Penn $20 million to fund CAR-T research. The results: high remission rates in trials testing CAR-T cells on leukemia and lymphoma patients.
“There were patients that were literally at death’s door and now they’re cured,” said Epstein.
The FDA is expected to issue a verdict on Novartis’ leading CAR-T therapy, CTL019, in October 2017. If approved, it would be the first-ever commercially available CAR-T.
But Epstein recognizes that CAR-T cells have limitations. Treatment can trigger overwhelming immune responses known as “cytokine storms,” and there have been a few deaths during CAR-T trials.
Plus, most CAR-T therapies aren’t scalable. Treatments are tailored to individual patients, and take time to make—time that a patient might not have.
“One of the downsides of the CAR-T cells [is] you need to take a sample of a patient’s blood. You need to bring it to the factory. You need to process it … and get it back to the patient. That process takes two-and-a-half to three weeks. These patients are on death’s door—three weeks is a really long time,” said Epstein.
In 2016, Epstein left Novartis amid a major reshuffling that split Novartis Pharmaceuticals—headed by Epstein—into separate pharmaceutical and oncology divisions. He figured he would take a year off to plan his next move.
That plan was cut short when Epstein was contacted by the founders of Flagship Pioneering—a firm that creates, funds, and supports life science companies. When he first heard their pitch, he was a bit skeptical.
“I got a text message from Noubar Afeyan, senior managing partner and CEO at Flagship,” said Epstein. “He wrote me a message about this really cool technology to make genetically engineered red blood cells. I sort of laughed under my breath—the last thing I wanted to do was make blood.”
But Afeyan convinced Epstein to come to Cambridge and meet with the Flagship partners, including Avak Kahvejian, who was CEO of Rubius Therapeutics—a company launched by Flagship. Kahvejian spoke to Epstein about Rubius’ Red Cell Therapeutics (RCT), a technology that takes red blood cells and modifies them to make thousands—sometimes millions—of copies of a specific protein, such as an enzyme or an antibody.
The approach could be used to target a variety of diseases, including cancers, autoimmune disorders, and enzyme-insufficiency diseases. Red blood cells deliver oxygen throughout the body, and thus, can reach a variety of tissues. The cells, which lack a nucleus, are typically not recognized by the immune system and have a natural lifetime of three months—properties that bode well for their use as safe and lasting therapies.
Epstein’s time at Novartis had taught him all the right questions to ask Rubius. Was their technology scalable? How would the company pick the proteins it would make? Would these modified red blood cells behave and function normally?
“They answered all these questions. As I was sitting in the room and came to understand more and more, it was sort of like, ‘I‘ve got to be part of this,’” said Epstein.
Part of the appeal was that Red Cell Therapeutics achieves what Epstein calls “the holy grail” of cellular therapy—off-the-shelf treatment, also known as allogeneic therapies. RCT uses red blood cells generated from O-negative donors, or the “universal donor” blood type. It can be prepared in bulk without the hassle of customizing therapies for each patient.
Epstein joined Flagship Pioneering as an executive partner in January and was recently named executive chairman of Rubius Therapeutics. Rubius plans to have its first red cell therapy in the clinic by late 2018, with others to follow in 2019. The technology has already shown promising early results in mouse models of multiple sclerosis and type 1 diabetes. And Rubius recently received $120 million in a major funding round led by Flagship and other life science firms.
Working with a small biotech company may seem a far cry from heading a division at Novartis, but Epstein relishes the new role — and finds it surprisingly similar to his old job.
“I had the opportunity to start Novartis Oncology from scratch — there might have been one oncologist in the entire company … I think that experience of building something from scratch and putting together a team was something I really enjoyed,” said Epstein. “Here at Rubius, I can recreate that and do the same thing—[it’s] the idea of [working with] a small entrepreneurial organization and guiding it through different phases of growth.”