Moderna has unveiled its first in vivo CAR-T program. Building on other groups’ ex vivo CAR-T data, the company plans to start clinical development of an off-the-shelf autoimmune disease prospect, dubbed “007,” next year.
Ex vivo, CD19-directed CAR-T cell therapies have achieved compelling outcomes in hard-to-treat lupus patients, driving surging interest in applying the modality to autoimmune diseases. Moderna has spotted an opportunity to leverage its mRNA expertise to create treatments that are similarly efficacious but free from the lymphodepletion and complex manufacturing that constrain access to ex vivo cell therapies.
The result is mRNA-6007, an in vivo CAR-T that Moderna unveiled at an investor event. The candidate targets CD7 on T cells, according to Jefferies. It consists of a lipid nanoparticle that delivers mRNA to CD4 and CD8 T cells and natural killer cells. The cells translate the mRNA, creating CAR-T cells that recognize and deplete pathogenic B cells.
Using cellular machinery to make the therapy “could overcome several limitations of conventional CAR-T therapies by considerably simplifying their manufacture and deployment, particularly in B-cell-mediated autoimmune diseases,” ODDO BHF analysts said in a note to investors. The analysts cautioned that the approach is still at a very early stage.
Moderna’s approach may require several doses, unlike one-time ex vivo treatments, but that difference may be offset by the convenience and scalability of its off-the-shelf therapy. The in vivo platform is the “ideal approach” when care accessibility and the potential for “a few doses to truly put an autoimmune patient into remission” are considered, Rose Loughlin, Ph.D., Moderna’s research chief, said at the event.
Other companies are applying in vivo CAR-T to oncology. Cancer is a focus for Moderna as it adapts to political pressures on infectious disease vaccines. Yet the biotech sees autoimmune disease as the best starting point for its in vivo CAR-T strategy, as David Berman, M.D., Ph.D., chief development officer at Moderna, explained.
“If you think about autoimmune diseases, the confirmatory trials and phase 3 trials are, of course, going to be very large,” Berman said. “The commercial opportunity is very large. And there’s no other company in the world who can really manufacture on that scale other than Moderna for mRNA-LNP, so it makes sense scientifically and it makes sense also commercially.”
Moderna is completing IND-enabling studies for mRNA-6007 and “conducting a series of pre-submission health authority engagements,” Lin Guey, Ph.D., the company’s chief scientific officer for therapeutics research, said. The candidate is scheduled to enter the clinic next year. Moderna will assess mRNA-6007 in a basket of B-cell-mediated autoimmune conditions, including lupus, Guey said.
The program is the “sentinel application” for Moderna’s in vivo aspirations, Guey said. Moderna tries to minimize biology risk when applying its platform to a new area. If the sentinel application succeeds, the biotech becomes more comfortable taking on biology risk in subsequent programs. Oncology and T-cell reprogramming are on Moderna’s roadmap of follow-on concepts that could build on mRNA-6007.