Carisma Therapeutics (CARM) Jefferies 2024 Global Healthcare Conference summary

Platform overview and scientific rationale

• Focus on engineered myeloid cells, specifically monocytes and macrophages, for oncology applications.

• Macrophages uniquely traffic to tumors, remodel the tumor microenvironment, and present antigens to T cells.

• Three mechanisms: direct tumor killing, microenvironment remodeling, and adaptive immune activation.

• Early clinical data show successful cell manufacturing, tumor trafficking, and immune remodeling.

Clinical development and data updates

• CT-0508 (HER2-targeted CAR macrophage) showed stable disease but no objective responses, likely due to underdosing and T cell exhaustion.

• Combination with pembrolizumab led to the greatest tumor shrinkage observed and increased T cell clonality.

• Corticosteroid use in early cohorts negatively impacted macrophage viability; new protocols now avoid steroids.

• Transitioning to CAR monocyte (CT-0525) approach for higher cell numbers, better tumor localization, and longer persistence.

Manufacturing and operational advantages

• CAR monocytes can be produced in higher quantities (up to 10 billion cells) and in a shorter timeframe (1 day vs. 8 days for macrophages).

• Monocytes show a 40-fold improvement in tumor trafficking and a tenfold increase in persistence compared to macrophages.

• Manufacturing improvements reduce costs and increase facility throughput.