Carisma Therapeutics (CARM) H.C. Wainwright 3rd Annual Cell Therapy Virtual Conference summary

Company background and technology evolution

• Founded nearly a decade ago to develop chimeric antigen receptor (CAR) macrophages, expanding to monocyte and in vivo approaches.

• Manufacturing shifted from ex vivo macrophages to monocytes, reducing production time to one day and enabling automation.

• Pipeline includes CT-1119 (mesothelin-targeted CAR monocyte therapy), CT-2401 (TIM4 for liver fibrosis), and in vivo CAR-M programs with Moderna.

• HER2-targeted program discontinued due to market changes, not safety or efficacy concerns.

Clinical data and learnings

• Phase 1 trial of CT-0508 (anti-HER2 CAR-macrophage) showed successful manufacturing, high CAR expression, and M1 phenotype.

• No dose-limiting toxicities or severe adverse events; only mild, transient CRS observed.

• Efficacy limited to stable disease, with best responses in HER2 3+ patients and significant, though transient, ctDNA reductions.

• Tumor microenvironment remodeling observed, with increased T cell recruitment and activation.

• Single-dose limitation identified; future trials will use repeat dosing every three weeks.

Pipeline strategy and next steps

• CT-1119 targets mesothelin, avoiding antigen loss issues seen with HER2 and enabling streamlined enrollment.

• CT-1119 uses minimally manipulated monocytes, improving persistence and tumor infiltration, with higher dosing possible.

• Enhanced CAR design and SIRPα knockdown incorporated to boost efficacy and overcome immune checkpoints.

• Phase 1 trial will dose patients every three weeks for up to five cycles, combined with anti-PD-1 therapy.