BIIB080 / Biogen, Ionis - LARVOL DELTA

2026 Anticipated Highlights Include (Businesswire) - "Results from FUSION study of ulefnersen for Fused in Sarcoma (FUS) Amyotrophic Lateral Sclerosis (ALS) (Otsuka)...Multiple Phase 2 data readouts, including IONIS-MAPTRx (BIIB080) in Alzheimer’s disease (AD) (Biogen) and new Phase 3 clinical trial initiations."

Clinical data • New P3 trial • Alzheimer's Disease • Amyotrophic Lateral Sclerosis

Drug Development. (PubMed, Alzheimers Dement) - P1, P2 | "The ongoing Phase 2 CELIA trial will assess the efficacy, safety, and tolerability of BIIB080 compared to placebo in participants with early AD."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Biomarkers. (PubMed, Alzheimers Dement) - P1, P2 | "However, these biomarkers are currently measured in CSF only, and evidence for their use as treatment-response measures is limited. Based on emerging tau biomarker advances and biomarker results from BIIB080, this presentation will provide future directions on the use and importance of tau biomarkers for development of therapies targeting tau."

Biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • MAPT • p-tau181

Biodistribution of radiolabeled MAPT antisense oligonucleotide BIIB080 following intrathecal administration in healthy adults (CTAD 2025) - No abstract available

Clinical • MAPT

A Study to Determine the Biodistribution, Safety, and Tolerability of a Microdose of Radiolabeled BIIB080 Co-administered With BIIB080 in Healthy Adults (clinicaltrials.gov) - P1 | N=5 | Active, not recruiting | Sponsor: Biogen | Recruiting ➔ Active, not recruiting

Enrollment closed

Innovative Phase 1b/2a Trial to Test Anti-Tau Agent BIIB080 in Corticobasal Syndrome (NeurologyLive) - P1b/2a | N=24 | "At the 2025 Alzheimer’s Association International Conference (AAIC)...investigators shared details on a new phase 1b/2a trial testing the safety and preliminary efficacy of BIIB080 (Biogen/Ionis)...as a potential treatment for corticobasal syndrome (CBS)...The study, a 6-month, randomized, double-blind, placebo-controlled trial, will primarily test the safety/tolerability of BIIB080, an antisense oligonucleotide, in a cohort of 24 patients with a clinical diagnosis of CBS...Overall, plasma p-tau217 was elevated in patients with CBS with positive Aß PET results (mean, 0.57 [SD, 0.43] pg/mL) or FTP PET (mean, 0.75 [SD, 0.30] pg/mL) to concentrations comparable to control individuals with AD (mean, 0.72 [SD, 0.37]), whereas PSP-RS and nfvPPA showed no increase relative to control....Results from CELIA are expected to come in 2026, according to Biogen."

P1/2 data • P2 data • Alzheimer's Disease • CNS Disorders • Dementia

BIIB080: the development of a tau-targeting antisense oligonucleotide in early AD (ASGCT 2025) - "Supported by the Neurologic and Opthalmic Committee"

PET imaging of antisense oligonucleotide distribution in rat and nonhuman primate brains using click chemistry. (PubMed, Sci Transl Med) - "The approach was evaluated in cynomolgus macaques using both the Malat1 test ASO and a candidate therapeutic ASO, BIIB080, targeting the microtubule-associated protein tau (MAPT) gene. PET imaging showed favorable tracer kinetics and specific binding to both ASOs in nonhuman primate (NHP) brain in vivo. These results suggest that the PET imaging tracer [18F]BIO-687 could show the distribution of intrathecally delivered ASOs in the rat and NHP brains."

Journal • Preclinical • MALAT1 • MAPT

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-MAPTRx in Patients With Mild Alzheimer's Disease (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Phase classification: P1/2 ➔ P1

Phase classification • Alzheimer's Disease • CNS Disorders

Biogen’s Investigational Tau-Targeting Therapy BIIB080 Receives FDA Fast Track Designation for the Treatment of Alzheimer’s Disease (GlobeNewswire) - "Biogen Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to BIIB080, an investigational antisense oligonucleotide (ASO) therapy targeting tau, for the treatment of Alzheimer’s disease.... The Phase 2 CELIA study is now fully enrolled, with a data readout expected in 2026."

Fast track • Alzheimer's Disease

A Study to Determine the Biodistribution, Safety, and Tolerability of a Microdose of Radiolabeled BIIB080 Co-administered With BIIB080 in Healthy Adults (clinicaltrials.gov) - P1 | N=5 | Recruiting | Sponsor: Biogen | Not yet recruiting ➔ Recruiting

Enrollment open

Drug Development. (PubMed, Alzheimers Dement) - "A QSP model was developed to integrate therapies targeting Aβ and tau pathologies in AD. The model can be utilized to explore dosing regimens to support the development of combination therapy."

Journal • Alzheimer's Disease • CNS Disorders • Aβ42 • p-tau181

Developing Topics. (PubMed, Alzheimers Dement) - "BIIB080, as a tau synthesis reduction drug, demonstrated promising results on tau biomarkers in individuals with moderate AD, along with favorable tolerability. These findings suggest its potential as a therapeutic intervention to target tau pathology and alter the course of AD. Further research is warranted to establish its clinical effectiveness and long-term safety profile."

Biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • CSF T-tau • p-tau181

A Study to Determine the Biodistribution, Safety, and Tolerability of a Microdose of Radiolabeled BIIB080 Co-administered With BIIB080 in Healthy Adults (clinicaltrials.gov) - P1 | N=5 | Not yet recruiting | Sponsor: Biogen | Trial completion date: Jul 2025 ➔ Jul 2026 | Trial primary completion date: Feb 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date

Ionis reports third quarter 2024 financial results (PRNewswire) - "WAINUA (WAINZUA in Europe) for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) achieved multiple commercial and regulatory milestones...Generated sales of $23 million and $44 million resulting in royalty revenue of $5 million and $10 million in the three and nine months ended September 30, 2024, respectively...IONIS-MAPTRx (BIIB080) enrollment complete in Phase 2 CELIA study in patients with early Alzheimer's disease (AD); data expected in 2026."

P2 data • Sales • Alzheimer's Disease • Amyloidosis • Cardiovascular • CNS Disorders

A Study to Determine the Biodistribution, Safety, and Tolerability of a Microdose of Radiolabeled BIIB080 Co-administered With BIIB080 in Healthy Adults (clinicaltrials.gov) - P1 | N=5 | Not yet recruiting | Sponsor: Biogen | Initiation date: Oct 2024 ➔ Jan 2025

Trial initiation date

CELIA: A Study to Learn About the Safety of BIIB080 Injections and Whether They Can Improve Symptoms of Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD Dementia Between 50 to 80 Years of Age (clinicaltrials.gov) - P2 | N=364 | Active, not recruiting | Sponsor: Biogen | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

CELIA: A Study to Learn About the Safety of BIIB080 Injections and Whether They Can Improve Symptoms of Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD Dementia Between 50 to 80 Years of Age (clinicaltrials.gov) - P2 | N=364 | Recruiting | Sponsor: Biogen | N=735 ➔ 364 | Trial completion date: Feb 2030 ➔ Jan 2029 | Trial primary completion date: Nov 2027 ➔ May 2026

Enrollment change • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

A Study to Determine the Biodistribution, Safety, and Tolerability of a Microdose of Radiolabeled BIIB080 Co-administered With BIIB080 in Healthy Adults (clinicaltrials.gov) - P1 | N=5 | Not yet recruiting | Sponsor: Biogen | Trial primary completion date: Jul 2025 ➔ Feb 2025

Trial primary completion date

Quantitative Systems Pharmacology Model for Therapies Targeting Aβ and Tau Pathologies in Alzheimer’s Disease (AAIC 2024) - "Furthermore, the model incorporates mechanisms of action for anti-Aβ mAbs, including aducanumab, lecanemab, donanemab and gantenerumab, and the tau-targeting ASO, BIIB080. A QSP model was developed to integrate therapies targeting Aβ and tau pathologies in AD. The model can be utilized to explore dosing regimens to support the development of combination therapy."

Alzheimer's Disease • CNS Disorders • Aβ42 • p-tau181

Exploratory clinical outcomes from BIIB080 (MAPT ASO) phase 1b multiple ascending dose and long-term extension study in mild Alzheimer’s disease (AAIC 2024) - "We report numerical differences favoring BIIB080 for high-dosed groups on clinical outcomes at completion of the MAD and LTE. Caution should be taken in interpretation given small sample size and use of external controls in the LTE. These data support investigation of BIIB080 in the CELIA phase 2 trial."

Clinical • Clinical data • P1 data • Alzheimer's Disease • CNS Disorders • Pain • MAPT

A Study to Determine the Biodistribution, Safety, and Tolerability of a Microdose of Radiolabeled BIIB080 Co-administered With BIIB080 in Healthy Adults (clinicaltrials.gov) - P1 | N=5 | Not yet recruiting | Sponsor: Biogen

New P1 trial

Biogen Highlights New Data at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) 2024 Annual Meeting (GlobeNewswire) - "Biogen Inc...announced it will present new data from its Alzheimer’s disease (AD) portfolio at the upcoming International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2024), taking place March 5-9 in Lisbon, Portugal and virtually. The presentations include new data for its oral small molecule inhibitor of tau aggregation (BIIB113)....Biogen presentations will provide new data on brain target engagement and the safety profile in healthy volunteers of an oral small molecule O-GlcNAcase (OGA) enzyme inhibitor intended to reduce tau aggregation (BIIB113). In addition to BIIB113, Biogen is researching the potential of tau reduction in AD with its investigational antisense oligonucleotide targeting the microtubule associated protein tau (MAPT) gene (BIIB080). Other presentations will discuss the long-term efficacy of lecanemab..."

Clinical data • Alzheimer's Disease • CNS Disorders

Biogen to Realign Resources for Alzheimer's Disease Franchise (GlobeNewswire) - "Biogen Inc...today announced plans to reprioritize its resources in Alzheimer’s disease (AD)....The company will continue to advance LEQEMBI (lecanemab-irmb), the first anti-amyloid beta treatment with FDA traditional approval in the United States, and will accelerate development of potential new treatment modalities, including its ASO targeting tau (BIIB080) and an oral small molecule inhibitor of tau aggregation (BIIB113). The company will discontinue the development and commercialization of ADUHELM (aducanumab-avwa) 100 mg/mL injection for intravenous use and will terminate the ENVISION clinical study....Biogen licensed aducanumab from Neurimmune and has terminated that license. The rights to aducanumab will revert to Neurimmune."

Discontinued • Licensing / partnership • Pipeline update • Alzheimer's Disease • CNS Disorders

CELIA: A Study to Learn About the Safety of BIIB080 and Whether it Can Improve Symptoms of Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD Dementia Between 50 to 80 Years of Age (clinicaltrials.gov) - P2 | N=735 | Recruiting | Sponsor: Biogen | Trial completion date: Dec 2026 ➔ Feb 2030 | Trial primary completion date: Dec 2026 ➔ Nov 2027

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia