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A9-3408

Development stage: Discontinued
Lead developer: Alpha-9 Oncology
Modality: Antibody-Radionuclide Conjugates → Antibody Conjugates → Antibody-Based Therapeutics
Administration: Intravenous

Overview

A9-3408 is a novel targeted alpha radiotherapeutic (TAT) developed by Alpha-9 Theranostics for the treatment of melanoma. It consists of the alpha-emitting radioisotope Actinium-225 ([225Ac]) conjugated to a ligand that targets the melanocortin 1 receptor (MC1R), a protein highly expressed in melanoma tumors with minimal expression in healthy tissues. By binding to MC1R, A9-3408 delivers high-energy alpha-particle radiation directly to the cancer cells, inducing lethal double-strand DNA breaks while sparing surrounding healthy tissue. The therapeutic program is supported by a companion diagnostic imaging agent, A9-3202 (a Gallium-68-based PET tracer), which is used to select patients based on MC1R expression levels. A9-3408 entered Phase 1 clinical development in December 2025 for patients with MC1R-positive melanoma who have progressed on standard therapies.

Brand names: [225Ac]Ac-A9-3408
Other names: Actinium-225 MC1R-targeted radiotherapeuticActinium225 MC1R-targeted radiotherapeuticActinium 225 MC1R-targeted radiotherapeutic

Targets

MC1R (Melanocortin Type 1 Receptor)

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