TRPH-222 is a novel, site-specific antibody-drug conjugate (ADC) targeting CD22, a B-cell-restricted sialo-glycoprotein that is an important modulator of B-cell signaling and survival, which is expressed on nearly all B-cell malignancies. CD22 is a clinically validated ADC target with potential in Non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). The compound itself combines a site-specific modified humanized antibody conjugated to a cytotoxic payload using SMARTag conjugation technology with Hydrazino-Pictet-Spengler (HIPS) chemistry and a proprietary 4AP linker.
Pre-clinical data have shown that this optimization of payload placement and linker composition, combined with the stability afforded by HIPS chemistry, leads to better tolerability and expanded therapeutic index. TRPH-222 is currently in a Phase 1 clinical study for patients with relapsed and/or refractory B-cell lymphoma.