PHASE I SBIR CONCEPT AWARD FOR LOGIC GATED MOLECULAR ADAPTOR SYSTEM FOR JMML TREATMENT

Juvenile myelomonocytic leukemia (JMML) is a rare and high-mortality hematologic malignancy affectingyoung children. Currently, the primary treatment for JMML is allogeneic hematopoietic stem celltransplantation (HSCT); however, relapse remains a significant risk following transplant.In the Concept phase of our research, Gencyte established the synNotch-controlled PMA CAR platform andgenerated preliminary in vitro proof-of-concept data for JMML treatment. In Phase I, we will conduct in vivoassays using immunocompromised mice to evaluate synNotch-controlled PMA CAR-T cells. We also plan tooptimize leads to reduce HAMA (human anti-mouse antibody) responses, improving safety for humanapplication. Then in vitro and in vivo functional assays will be conducted on the optimized leads. Preclinicaldevelopment will follow, focusing on producing GLP/GMP-grade materials and completing IND-enablingstudies to support an IND application.