The Next Step in Targeted Therapy

Antibody-oligonucleotide conjugates (AOCs) combine the tissue selectivity of antibodies with the gene-regulating capabilities of short interfering RNA (siRNA) or antisense oligonucleotides (ASOs). The antibody identifies cell surface receptors, the linker delivers the RNA cargo, and the RNA suppresses disease-causing RNA within the cell. The key industry innovation lies in expanding the delivery scope of RNA therapies, previously limited to the liver, to muscles and the central nervous system.

Avidity's Clinical Validation

Delpacibart etedesiran (del-desiran·AOC 1001), an investigational AOC from Avidity Biosciences without a commercial brand, delivers siRNA to muscle via a transferrin receptor 1 (TfR1) antibody to reduce toxic DMPK RNA. The HARBOR Phase 3 trial (NCT06411288) for myotonic dystrophy type 1 (DM1) enrolled 159 patients and began in May 2024, with a primary completion expected in August 2026. Del-brax (AOC 1020) is a Phase 1/2 candidate targeting DUX4 RNA for FSHD, and del-zota (AOC 1044) is a Phase 2 asset delivering PMO for DMD exon 44 skipping.

Competition with Dyne

Zeleciment basivarsen (z-basivarsen·DYNE-101) from Dyne Therapeutics (DYN) is a FORCE platform candidate combining a TfR1-binding Fab with a DMPK-targeting ASO. The FDA granted Fast Track designation on January 21, 2025, and Breakthrough Therapy designation on June 17, 2025. The HARMONIA Phase 3 trial, enrolling approximately 150 patients, began dosing in July 2026. Current standard-of-care for DM1 remains symptomatic control with drugs like mexiletine. Competing pipelines include Vertex Pharmaceuticals (VRTX)'s VX-670 in Phase 2 and Sarepta Therapeutics (SRPT)'s ARO-DM1 in Phase 1/2.

Market and Regulatory Inflection Point

The global AOC market is projected to grow from $3.42 billion in 2025 to $5.26 billion in 2030, with a CAGR of 8.89%. As of September 1, 2026, no therapeutic AOCs have received FDA, EMA, or PMDA approvals, nor have any AdComms voted on related applications. Thus, the first approval will serve as a platform validation event, establishing manufacturing, safety, and biomarker standards for antibody-based extrahepatic RNA delivery.