Abata Therapeutics has launched with $95 million in series A funding to take cell therapy into a new realm: the treatment of multiple sclerosis.
The investment comes primarily from Third Rock Ventures, which provided the seed funding for Abata. ElevateBio, a company that specializes in manufacturing cell therapies, has also invested and is helping Abata develop its production process. The company started quietly 3 years ago and is still in preclinical stages, but hopes to have safety data by 2024.
Abata’s technology involves engineering regulatory T cells. T regs, as these immune cells are often called, help balance the immune response by tamping down immune activity. Several companies are investigating how to manipulate these cells as a way to treat the immune overreaction that characterizes inflammatory and autoimmune diseases.
“They’re essentially the ideal therapy for an autoimmune disease,” Abata CEO Samantha Singer says about T regs. “They can promote repair as well as stop tissue destruction, and they last a long time. For a chronic illness, they’re good and durable.”
Abata’s primary disease target is multiple sclerosis in people who have later-stage, non-relapsing disease, but the company is also exploring how to use its technology to treat type 1 diabetes and inclusion body myositis, an inflammatory disease that leads to muscle damage.
Multiple sclerosis is an autoimmune disease that affects the brain, the spinal cord, and the optic nerve, says Abata Chief Medical Officer Richard Ransohoff, who has studied the disease for many years. In MS, an overactive inflammatory response damages myelin, the protective covering around nerves. That loss exposes nerve fibers, leading to scarring.
It’s a slowly progressing disease. Early on, people alternate between relapses and remissions. After a while, the relapses and scarring stop, but the disease still progresses, Ransohoff says, and people continue to lose nerve function.
Current MS treatments include antibodies that block immune function, several small-molecule medications, and injectable proteins such as interferon and glatiramer acetate, a mixture of peptides that is similar to the myelin basic protein. Most available treatments work on earlier stages of the disease, Ransohoff says.
To develop T regs into an MS therapy , Abata scientists plan to take the cells from a person who has MS, engineer them to carry a molecule called a T-cell receptor that is specific to a part of the myelin basic protein, grow them in large quantities, and then reintroduce them into that person.
The central nervous system does have immune cells coursing through it, but in people with MS, T regs aren’t found in areas of inflammation, Singer says. Based on the company’s preclinical work, Singer and Ransohoff think the engineered T regs will travel through the cerebrospinal fluid, get to the sites of inflammation, and dampen the inflammatory response.
Jason Bock, a former drug industry scientist and cell-therapy expert at The University of Texas MD Anderson Cancer Center, credits Abata for signing up a manufacturing partner so early in the game. Cell therapies are complicated. The conditions under which cells need to be grown before putting them back into people are variable and sometimes quite finicky.
Several companies in the past year and a half have struggled to win US Food and Drug Administration approvals for cell therapies because of manufacturing issues. Pairing with ElevateBio, Bock says, allows Abata to work on its therapy, rather than try to manage both R&D and manufacturing.
Safety is always a concern with cell therapies, cautions Jamie Spangler, a bioengineer at Johns Hopkins University who is working on antibodies that stimulate T regs. One of the things T regs do is release immune-suppressing cytokines, which may travel outside the disease area and suppress the immune system elsewhere.
Another issue with T regs is that they need a lot of the cytokine interleukin-2 to survive, Spangler says. It’s possible that people who are treated with Abata’s T cell therapy may need their IL-2 levels boosted, and that can cause side effects.
Ransohoff says Abata is concerned about safety and notes that in human trials, people who have received large amounts of non-engineered T regs have had no safety issues. Singer says the company is working to prevent the possibility that some of its engineered T regs will become unstable and turn instead into T cells that promote inflammation.
Safety concerns aside, what Abata is trying to do is impressive, Spangler says, and while nothing is certain in cell therapy, the company has the expertise in T-cell biology to give it a good shot.
“They’re taking T regs, which is what’s deficient in MS, and they’re reintroducing them in a very specific and directed way,” she says. “So, I think if anything could work, this is a great opportunity. You’re providing everything that would be needed to be able to fight the disease.”