Carisma Therapeutics (CARM) Chardan's 8th Annual Genetic Medicines Conference summary

Platform overview and differentiation

• Focuses on engineering macrophages and monocytes to express CARs, enabling multi-modal tumor targeting and immune modulation.

• Macrophages can directly kill tumor cells, access solid tumors, remodel the tumor microenvironment, and drive adaptive immune responses.

• Manufacturing process allows for rapid, reproducible generation of large numbers of M1-polarized cells, completed in one day.

• Transitioned from ex vivo differentiated macrophages to direct monocyte transduction for improved efficiency.

Lead oncology program: CT-0525

• CT-0525 is an ex vivo autologous CAR-Monocyte therapy targeting HER2-overexpressing solid tumors.

• Phase I trial uses a basket design with dose escalation (3B to 10B cells), focusing on safety, tumor trafficking, and persistence.

• Early data from predecessor CT-0508 showed tumor trafficking, ctDNA reduction, and stable disease in late-stage patients.

• Addition of pembrolizumab improved T cell responses and is being incorporated into future cohorts.

• Data from current cohorts expected by year-end, with cohort three (repeat dosing plus pembrolizumab) planned for next year.

In vivo oncology and Moderna collaboration

• Collaboration with Moderna leverages mRNA-LNP technology for off-the-shelf in vivo CAR-M therapies.

• Five-year partnership covers 12 oncology targets, with $180M upfront, $3B in milestones, and full research funding.

• Preclinical proof-of-concept demonstrated effective mRNA delivery to myeloid cells and tumor control in HER2 models.

• First development candidate targets GPC3 in hepatocellular carcinoma, chosen for its liver localization and antigen properties.

• Program has transitioned to Moderna for preclinical and manufacturing work, with Carisma focusing on new targets.