Most cell therapies in development use a T cell or some other type of immune cell that has been engineered to perform a specific therapeutic task. Rubius Therapeutics makes its cell therapies from red blood cells, which may offer advantages over immune cells. Rubius’ pursuit of cell therapies based on red blood cells has had some bumps in the road, and while the biotech isn’t giving up on such therapies, it is now abandoning its current process for making them.
Adoption of a new RBC therapy platform comes with a corporate restructuring which completes work on two cancer programs that have reached early clinical testing in advanced solid tumors. Cambridge, Mass.-based Rubius will maintain its focus on cancer, and a new lead program is already in preclinical development with the new manufacturing technology, CEO Pablo Cañoni said on a conference call Tuesday.
Eliminating Rubius’ old way of making red blood cell therapies in favor of the new technology will lead to layoffs. Rubius is reducing its headcount by about 75%. According to the company’s annual report, the number of employees was 269 as of January 31. Of these full-time employees, 225 work in research and development. IN regulatory submission, Rubius said most of those losing their jobs were currently working on RTX-240 and RTX-224, the company’s two clinical-stage cancer cell therapies. The cost-saving measures are expected to keep Rubius cash flowing until the end of 2023, when the company should have more details on its new flagship program and others in the works.
Turning the body’s cells into therapies is still a relatively new concept. CAR T therapy, created by engineering a patient’s own T cells to recognize tumors, won its first FDA approvals in 2017. Around the same time, Rubius, a product of venture capital firm Flagship Pioneering, was working to to reach the clinic with its red blood cells designed to carry therapeutic proteins.
Red blood cells that naturally circulate in the body have a lifespan of up to 120 days. This means that a therapy based on such cells offers the potential for a long-lasting effect. Rubius developed a way to make his cells from blood stem cells that come from O negative donors. The use of cells from this universal donor blood group is intended to reduce the risk of triggering an immune response. Rubius failed in its first attempt at a red blood cell therapy the company was developing for the rare disease phenylketonuria. Manufacturing delays at a third-party company were among the factors that led Rubius to “deprioritize” rare disease two years ago and is shifting its focus to cancer and autoimmune diseases.
Producing red blood cells in bioreactors takes about three weeks, Cañoni said. This work uses lentiviral vectors to construct the cells, and the whole process is also expensive, he added. A few years ago, many cell therapy developers wanted to acquire or build their own manufacturing facilities, thinking that having such capabilities would save time and money compared to outsourcing the work. Ruby was among them.
Rubius raised more than $240 million from its extended IPO in 2018, which was priced at $23 per share. Part of the proceeds from the IPO was earmarked for the purchase of a production base. Shortly after going public, Rubius they made a deal to purchase from Alexion Pharmaceuticals a 135,000-square-foot manufacturing facility in Smithfield, Rhode Island. Rubius promised to invest up to $155 million at the site, which was expected to employ up to 150 people. The company’s new manufacturing process may render the site unnecessary. This process begins with normal, healthy red blood cells obtained from a blood bank. These cells are engineered with recombinant proteins using chemical conjugation technology that attaches proteins to cell membranes.
“So it’s simpler, it’s cheaper, it’s faster,” Cañoni said. “And it doesn’t require us to have a manufacturing facility on the scale that we have in Rhode Island right now.” It’s a much simpler process that can be partially outsourced, and over time we’ll decide if there’s any component that needs to be in-housed, but we don’t believe that at this stage.”
Rubius is now exploring a possible sale of its Rhode Island facility. In addition to the manufacturing advantages of its new technology, the new platform may also offer longer-lasting benefits and the potential for higher doses, said Larry Turka, chief scientific officer and head of research and translational medicine at Rubius. Preclinical studies so far show that these cells have longer circulation times, which the company expects will lead to higher circulation times in clinical testing, he explained. Turka added that the simplicity and speed of the new manufacturing process allows Rubius to escalate the therapy to higher doses than was possible with earlier Rubius technology.
In the coming months, Rubius expects to produce new preclinical data, including nonhuman primate data, with cell therapies that come from the new platform. By the end of the year, Cagnoni said Rubius should be able to provide an update on plans for an exploratory application of a new drug for its flagship cancer program. Type 1 diabetes continues to be the leading disease target for Rubius’ autoimmune research.
The six patients in Rubius’ cancer programs who reached early-stage testing will continue to receive the experimental therapy until their disease progresses or they drop out of the clinical trial, Cañoni said. Rubius expects to complete the layoffs in November. In a regulatory filing, Rubius said it was unable to make a “good faith determination” of how much the restructuring would cost. According to Rubius’ second-quarter financial results report, the company had $62.2 million in cash and cash equivalents as of June 30.
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