Where Are They Now? Carisma Therapeutics
By Ben Comer, Chief Editor, Life Science Leader
Then: In a 2021 “Companies To Watch” article written by Wayne Koberstein, Carisma Therapeutics CEO Steven Kelly spoke about his three-pronged mandate to fund the (then) privately held company, build a team, and define a purpose. “Our purpose was to translate the discoveries made [by Michael Klichinsky and Saar Gill] at the University of Pennsylvania into a real therapeutic and get it into humans,” which meant taking a “venture project” into a fully GMP process that the FDA would approve for human clinical testing.
That project was a CAR-M cell therapy — “M” for microphages, as compared with the more well-known CAR-T approach — powered by the idea that macrophages could be a more effective tool for attacking solid tumors. After Klinchinsky and Gill produced promising results in animal and tumor models and cofounded the company in 2016, Kelly, an experienced industry executive, joined Carisma as CEO in 2017. At the time of publication (April 2021) Carisma had raised a total of $120 million from a broad base of investors and had dosed the first patient with CT-0508, a CAR-M targeting HER2-overexpressing solid tumors.
CT-0508 was a first-in-human clinical program, and a chance for the first CAR-engineered macrophage, or CAR-M, to prove its utility as a new approach to treating solid tumors, a target that CAR-T therapies haven’t adequately addressed. “We believe that, given the mechanism of macrophages, the ability to traffic, the ability to kill directly through phagocytosis, the ability to warm up the tumor microenvironment, and the ability to generate an adaptive immune response, they are ideally suited for solid tumors, and we plan to show that clinically,” said Kelly.
Now: Three years later — stretching across one of the most difficult funding periods ever for early-stage cell therapy companies — Carisma is working toward the release of Phase 1 data in support of CT-0525, a CAR-Monocyte (monocytes are precursor cells to macrophages); has presented preclinical proof-of-concept data supporting mRNA/LNP in vivo CAR-M therapy (via a collaboration with Moderna); and has become a publicly traded company through a merger with Sensen Bio. There have been learnings, and bumps, along the way.
In April 2024, Carisma ceased development of its original lead candidate, CT-0508 (and ended a study of CT-0508 in combination with Merck's Keytruda), in favor of prioritizing CT-0525, which Kelly said offers a “significant advancement in CAR-M treatment” over CT-0508; the CAR-Monocyte (CT-0525) potentially offers a 2,000 fold increase in total exposure in the anti-HER2 program compared with the CAR-Macrophage (CT-0508). In June, CT-0525 received Fast Track designation from the FDA, and in September, Carisma and Moderna expanded their collaboration into autoimmune diseases.
Moderna and Carisma’s initial collaboration, announced in January 2022, was established to develop in vivo (or inside the body) CAR-Monocytes in oncology, leveraging Moderna’s mRNA/LNP platform and Carisma’s CAR-M technology together. The expanded collaboration into autoimmune diseases — Moderna has nominated two targets — as well as the nomination of an oncology target (Glypican-3, a protein overexpressed in hepatocellular carcinoma, the most prevalent type of liver cancer and the fastest-rising cause of cancer-related death in the U.S.), triggered payments of $40.4 million and $2.0 million that will help fund the company into the third quarter of 2025.
CAR-Monocytes have additional advantages over CAR-Macrophages, according to Carisma, including reduced manufacturing time. The company’s CAR-Monocyte manufacturing platform can potentially manufacture up to 10 billion cells from a single apheresis and utilizes a rapid, single-day manufacturing process. Manufacturing at scale continues to be a challenge for many development-stage cell therapy companies. Although it’s still early, CT-0525’s Phase 1 data release (expected by the end of 2024), and the Company’s ongoing collaboration with Moderna, cement Carisma’s status as a company to watch in the search for better solid tumor therapeutics.