PPMX-T003

Furthermore, NCO4A and LC3-II were induced following antibody treatment, and ferritin degradation was inhibited by lysosomal inhibitors, suggesting that ferritin degradation depends on autolysosomal system activation. Here, we introduce ferroptosis as one of the potential mechanisms of PPMX-T003 antibody, which is promising for future therapeutic antibodies targeting a wide range of leukemia and cancers, including ATLL.

P1/2, N=7, Recruiting, Hiroshima University Hospital | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2025 --> Mar 2026

Except for an antibody drug conjugate (CX-2029), this is the first-in-class trial of an unmodified human antibody other than the murine P1a trial conducted in the 1990s. AEs are mild as observed within the level of previous healthy volunteer's trial. Efficacy observed in all erythroid parameters including hematocrit, hemoglobin and other parameter shown symptoms seen in iron deficiency anemia. This antibody can specifically suppress erythrocyte differentiation by inhibiting iron influx in the target erythroid lineage, which cells are highly expressed TfR1, without any significant AE on other normal organs with low expression level of TfR.

PPMX-T003, a humanized anti-TfR1 monoclonal antibody, showed remarkable therapeutic efficacy in a preclinical setting using ANKL-PDXs. These findings indicate that the liver, a non-canonical hematopoietic organ in adults, serves as a principal niche for ANKL, and that inhibition of the Tf-TfR1 axis is a promising therapeutic strategy for ANKL.

P1/2, N=6, Recruiting, Hiroshima University Hospital