Carisma Therapeutics Inc. presented promising preclinical data on engineered macrophages for treating liver fibrosis at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting® 2024. These results support the anti-fibrotic potential of Carisma's engineered macrophages in multiple liver fibrosis models. The data suggest a novel, off-the-shelf potential treatment option for patients with fibrotic liver disease, including advanced metabolic dysfunction-associated steatohepatitis (MASH).
New preclinical results demonstrated that macrophages can be genetically engineered to target specific key pathways underlying liver disease with factors including TIM4, relaxin, and IL10. Engineered TIM4-expressing macrophages corrected defective efferocytosis in MASH, showing potent anti-fibrotic activity. This mechanism addresses a critical aspect of liver disease progression.
A single dose of macrophages expressing TIM4, alone or together with relaxin, significantly reduced liver fibrosis and hepatic stellate cell activation in the translationally relevant choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) MASH model. The engineered macrophages were well tolerated and outperformed non-engineered cells in all models. Carisma expects to nominate a development candidate for its liver fibrosis program in the first quarter of 2025.
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