TRPH-222: A Promising Anti-CD22 ADC with Potent Anti-Tumor Effects and High Tolerance in NHL Xenografts and NHPs

CD22 is a glycoprotein found exclusively in B-cells, from their early stages to maturity, but is less present in plasma cells. It is prevalent in several B-cell related malignancies, such as NHL, DLBCL, MCL, MZL, and others, making it a promising target for ADC therapies. However, previous attempts have not been clinically successful due to a poor therapeutic index. TRPH-222 is a novel ADC with a unique site-specific linkage that attaches a maytansinoid payload to an anti-CD22 antibody, achieving a DAR of 2.0. This study aimed to assess the anti-tumor efficacy and tolerability of TRPH-222.

In a xenograft model, TRPH-222 significantly reduced tumor volume at doses of 1, 3, and 10mg/kg, outperforming rituximab. It also induced tumor stasis in other B-cell lymphoma models. In non-human primates, TRPH-222 was well tolerated at various doses, with no adverse effects on clinical observations or body weight. Minor increases in AST and ALT were noted at higher doses, but no significant liver issues were found.

Preliminary pharmacokinetic data indicate that TRPH-222 is stable, with a long half-life and stable linker in vivo. The study suggests that TRPH-222 has potent anti-tumor activity against B-cell lymphomas and is well-tolerated, with a large therapeutic window. Ongoing safety studies are preparing for clinical trials in 2018. The high doses tolerated in monkeys, which are significantly higher than for most ADCs, indicate that TRPH-222 could offer a superior therapy for NHL and a leading ADC technology.