Antisense oligonucleotides (ASOs) are short synthetic single-stranded nucleic-acid molecules designed to bind complementary messenger RNA and either block translation, alter splicing, or trigger degradation of the target transcript. As a modality, ASOs sit adjacent to peptides in the therapeutic taxonomy: both are synthetic biomolecules that operate below the antibody size threshold, share manufacturing infrastructure with peptide synthesis, and increasingly ride the same delivery platforms (Denali's Oligonucleotide TransportVehicle shuttles ASOs across the blood-brain barrier through the same TfR1 mechanism used for peptide-conjugate CNS delivery).
The 2026 ASO landscape spans several therapeutic areas. Biogen's diranersen (BIIB080) is an intrathecally administered anti-MAPT ASO for Alzheimer's disease; the Phase 2 CELIA study presented at AAIC 2026 on Tuesday July 14 missed its primary endpoint on CDR-SB dose response but showed strong tau pathology reduction and cognitive benefit particularly at the lowest 60 mg q24w dose. AstraZeneca and Ionis' Wainua (eplontersen) missed the primary composite endpoint in the CARDIO-TTRansform Phase 3 study in transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) announced July 9, though the drug remains FDA-approved for hereditary ATTR polyneuropathy. Ionis' Tryngolza (olezarsen) received FDA approval June 24 for severe hypertriglyceridemia.
Stories here cover ASO trial readouts, delivery platform advances, and the modality's positioning relative to peptides. See [[tau]], [[alzheimers-disease]], and [[blood-brain-barrier]] for adjacent threads.
Biogen (NASDAQ: BIIB) presented full Phase 2 CELIA study data for diranersen (BIIB080), an investigational tau-targeting antisense oligonucleotide (ASO) delivered intrathecally, at AAIC 2026 in London on Tuesday July 14, 2026 during the Developing Topics in Phase 2 Clinical Trials Session (2:00-3:30 PM BST). The 76-week placebo-controlled study evaluated three doses (60 mg every 24 weeks, 115 mg every 24 weeks, and 115 mg every 12 weeks) and did not meet its primary endpoint of dose response on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at Week 76. Strong reductions in tau pathology occurred across all studied doses, generally consistent with the Phase 1b study. Prespecified analyses of cognitive endpoints demonstrated slowing of clinical decline across all doses, with the effect particularly pronounced at the lowest 60 mg q24w dose. Biogen framed the results as the first randomized Phase 2 evidence of a tau-directed therapy showing both biomarker impact and cognitive benefit, and plans to advance diranersen to registrational Phase 3 development.
Biogen (NASDAQ: BIIB) will present Phase 2 CELIA study data for diranersen (BIIB080), an investigational tau-targeting antisense oligonucleotide (ASO), at AAIC 2026 in London during the Developing Topics in Phase 2 Clinical Trials session on Tuesday July 14, 2:00–3:30 PM BST. The 18-month CELIA study evaluated diranersen in patients with early Alzheimer's disease and is the first study to show reduction in tau pathology and cognitive benefit for a tau-targeted therapy. Biogen will present clinical, biomarker, and safety data that build on the May 2026 topline announcement and further characterize the molecule as the program advances toward Phase 3 development. Diranersen targets MAPT RNA to reduce tau production at its source, a differentiated approach to addressing abnormal tau both inside and outside neurons. The CELIA readout is a peptide-adjacent nucleic-acid biologic milestone that shifts the tau treatment conversation from 'reducing pathology' to 'reducing pathology and moving cognition.'
AstraZeneca and Ionis Pharmaceuticals announced Thursday July 9, 2026 that the Phase 3 CARDIO-TTRansform trial of Wainua (eplontersen) did not meet its primary efficacy endpoint in adults with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). The trial enrolled over 1,400 patients and was the largest Phase 3 study conducted in the ATTR-CM population to date; the primary endpoint was a composite of cardiovascular mortality and recurrent CV clinical events through 140 weeks compared with placebo. Prespecified subgroup analyses showed nominally significant reductions in composite events with eplontersen monotherapy versus placebo, while patients also receiving a baseline TTR stabilizer showed no incremental effect. Eplontersen is an antisense oligonucleotide (a nucleic-acid therapeutic modality distinct from peptides but adjacent in the metabolic-and-cardiovascular therapeutic territory this site tracks); the drug is already FDA-approved as Wainua for hereditary transthyretin amyloidosis polyneuropathy. Full CARDIO-TTRansform results will be presented at the European Society of Cardiology (ESC) Congress in August 2026. AstraZeneca and Ionis shares fell on the readout.
Aligos Therapeutics presented additional EASL 2026 data on its chronic hepatitis B (HBV) combination strategy. An analog of ALG-170675, a potential best-in-class antisense oligonucleotide (ASO), demonstrated additive-to-synergistic effects when combined with ALG-001075 (the active parent moiety of pevifoscorvir sodium, a capsid assembly modulator). Separately, 40% of HBeAg-positive chronic HBV patients treated with pevifoscorvir sodium for 48 weeks reached HBsAg reductions low enough to potentially qualify for ASO treatment — supporting a sequencing strategy toward functional HBV cure where the capsid modulator lowers viral antigen load before the ASO finishes the job. The data complements the ALG-055009 THR-β MASH results (46.2% liver-fat reduction) Aligos presented earlier in the week. The combination-and-sequencing approach mirrors the broader trend in liver disease toward layered mechanisms rather than single-agent therapy, and positions Aligos across the HBV, HDV, and MASH liver-disease franchises.