Carisma Therapeutics has been working for years to develop cell therapies using macrophages, immune cells that are better at attacking solid tumors than the T cells that currently dominate the industry. In a partnership with Moderna, now expanded to two undisclosed autoimmune targets, the biotech hopes to seriously simplify cell therapy by bypassing the need to culture patient cells out of the body.
The technique is called in vivo CAR-M therapy.
"The nomination of the two autoimmune targets is a significant milestone in our mission to harness the power of macrophages to treat a broader range of diseases,” Carisma President and CEO Steven Kelly said in a Sept. 10 release. “Our innovative CAR-M technology has the potential to revolutionize the treatment landscape for patients suffering from these debilitating conditions."
The two autoimmune targets will be exclusively partnered with Moderna, the release said, while Carisma will retain all rights in autoimmune diseases beyond these targets.
CAR-M therapy, like CAR-T cell therapy, involves collecting immune cells from patients and genetically modifying them to target a disease-causing cell, like a cancer cell. These reprogrammed cells are then reintroduced into the patient and set loose to fight the disease.
Conversely, Moderna has been working with Carisma to reprogram macrophages while they’re still inside a patient’s body by using mRNA.
Under the expanded partnership, the two companies plan to use Moderna’s mRNA-delivery nanoparticle platform to transport mRNA that codes for autoimmune targets directly into macrophages. It's expected that the macrophages will naturally turn the mRNA into an antigen protein that they would then target on the overreactive immune cells that cause autoimmune diseases. In this way, macrophages wouldn't have to be removed and engineered to express the antigen in the lab.
Under the terms of the deal, Carisma will receive research funding from Moderna and could also receive other payments if certain development, regulatory and commercial milestones are met, along with royalties from net sales, according to the release.
Carisma is in charge of the discovery and optimization of development candidates while Moderna will lead the clinical development and commercialization of any therapeutics that result from the partnership, the release said.
In June, Carisma received a Fast Track Designation from the FDA for a CAR-M therapy treating HER2-overexpressing solid tumors; initial phase 1 data are expected later this year. At the Society for Immunotherapy of Cancer’s annual conference in Nov. 2023, Carisma presented data showing that mice given CAR-M mRNA either directly into tumors or intravenously saw their macrophages successfully reprogrammed and tumors shrink.
There are currently no approved CAR-M therapies. A phase 1 adenocarcinoma trial with another mRNA-based CAR-M, MCY-M11, was terminated by the sponsor, MaxCyte, in 2021 due to a shift in focus.