ArriVent BioPharma (Nasdaq: AVBP), based in Newtown Square, Pennsylvania, announced IND clearance from the US FDA for ARR-002, a dual-target tetravalent antibody-drug conjugate directed against MUC16 and NaPi2b, with an initial clinical focus in ovarian and endometrial cancers. The company said it expects to initiate a Phase I trial and dose the first patient in the second half of 2026.
ARR-002, also designated AV-P138-ADC, is designed as a tetravalent construct in a 2+2 bispecific format, simultaneously engaging both MUC16 — widely known as CA-125 — and NaPi2b, a sodium-dependent phosphate transporter encoded by SLC34A2. Both antigens are reported to be highly expressed on ovarian and endometrial tumor cells with limited expression in normal tissues. The molecule uses site-specific conjugation to vcMMAE at a drug-to-antibody ratio of 4, a design intended to deliver a homogeneous, stable construct with controlled payload release following internalization.
The scientific rationale centers on limitations observed with single-target ADCs. Heterogeneous antigen expression across tumor cells is a recognized mechanism of resistance or incomplete response for agents that rely on a single surface marker. By engaging two targets simultaneously, ARR-002 is designed to increase avidity, improve internalization efficiency, and reduce the probability of tumor escape through downregulation of either target alone. ArriVent said preclinical data presented at the 2026 American Association for Cancer Research Annual Meeting — in a joint presentation with Aarvik Therapeutics, the company's collaborator on the construct — demonstrated effective simultaneous engagement of both targets, enhanced internalization relative to single-target antibody controls, and superior in vivo efficacy versus single-target ADCs in the OVCAR-3 xenograft model. A tolerability assessment in cynomolgus monkeys showed reversible hematologic findings at a higher maximum tolerated single dose compared to other approaches in development, which the company characterized as a potentially wider therapeutic window, though cross-species extrapolation carries inherent limitations.
The ADC landscape for ovarian cancer
The ovarian cancer ADC field has a defined benchmark in mirvetuximab soravtansine (Elahere), developed by ImmunoGen and now marketed by AbbVie following its acquisition. Mirvetuximab targets folate receptor alpha and received full US FDA approval in March 2024 for platinum-resistant ovarian cancer with high FRα expression. It represents the first and currently only approved ADC in this setting, but its eligibility is constrained by the FRα biomarker threshold, leaving a substantial proportion of patients — those with low or absent FRα expression — without a targeted ADC option.