Carisma, Moderna expand cell therapy collaboration to autoimmune diseases

Carisma Therapeutics has been pioneering the development of cell therapies using macrophages, immune cells that show promise in attacking solid tumors more effectively than T cells, which currently dominate the field. Recently, Carisma expanded its partnership with Moderna to include two undisclosed autoimmune targets, aiming to simplify cell therapy by eliminating the need to culture patient cells outside the body. The approach, known as in vivo CAR-M therapy, is anticipated to revolutionize the treatment landscape.

Steven Kelly, Carisma's President and CEO, highlighted the significance of this milestone in a release dated September 10. He emphasized that the nomination of the two autoimmune targets aligns with their mission to utilize the potential of macrophages to treat a wider array of diseases. According to the release, these two targets will be exclusively partnered with Moderna, while Carisma retains rights to other autoimmune diseases beyond these targets.

In traditional CAR-M therapy, immune cells are collected from patients, genetically modified to target disease-causing cells, and then reintroduced into the patient to combat the disease. However, under the new partnership, Moderna and Carisma plan to reprogram macrophages directly within the patient’s body using mRNA technology. Moderna's mRNA-delivery nanoparticle platform will be employed to transport mRNA coding for autoimmune targets directly into macrophages. These macrophages are expected to produce an antigen protein that targets overreactive immune cells responsible for autoimmune diseases, thus negating the need to remove and engineer the macrophages externally.

Under the terms of this deal, Carisma will receive research funding from Moderna and may also receive additional payments contingent on achieving specific development, regulatory, and commercial milestones. There are provisions for royalties from net sales as well. Carisma will handle the discovery and optimization of development candidates, while Moderna will take charge of clinical development and commercialization.

In June, Carisma achieved a significant milestone when the FDA granted Fast Track Designation for its CAR-M therapy aimed at treating HER2-overexpressing solid tumors. Initial phase 1 data for this therapy is anticipated later this year. At the Society for Immunotherapy of Cancer's annual conference in November 2023, Carisma presented promising data. Mice treated with CAR-M mRNA, either directly into tumors or intravenously, showed successful reprogramming of macrophages and subsequent tumor shrinkage.

Currently, there are no approved CAR-M therapies. Prior efforts, such as a phase 1 trial for adenocarcinoma using another mRNA-based CAR-M, MCY-M11, were terminated by sponsor MaxCyte in 2021 due to a strategic shift in focus. This expanded partnership between Carisma and Moderna represents a significant step forward in leveraging macrophages for the treatment of autoimmune diseases and potentially improving outcomes for patients suffering from these debilitating conditions.