BIIB080 / Biogen, Ionis - LARVOL DELTA

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

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

JAMA Neurology Publishes Data on Biogen’s Investigational Antisense Oligonucleotide Targeting Tau (Biogen Press Release) - "JAMA Neurology published biomarker data from the placebo-controlled period (PCP) and long-term extension phase of the BIIB080 Phase 1b study of the antisense oligonucleotide (ASO) which targets tau pre-mRNA in early-stage Alzheimer's disease (AD). The publication follows the presentation of late-breaking study results at the 2023 Clinical Trials on Alzheimer's Disease (CTAD) meeting which included data from multiple exploratory endpoints of cognition and activities of daily living. This publication includes preliminary data in 46 patients which showedthat the investigational therapy substantially reduced soluble and aggregated pathologic tau in patients with mild AD."

P1 data • Alzheimer's Disease • CNS Disorders

Exploratory clinical outcomes from BIIB080 (MAPT ASO) phase 1b multiple ascending dose and long-term extension study in mild Alzheimer's disease (CTAD 2023) - P1/2, P2 | "BIIB080 phase 1b CSF biomarkers showed target engagement, and tau PET data suggested potential disease-modification[3]. Now we report numerical differences favoring BIIB080 for high-dosed groups on multiple cognitive and functional scales at completion of the MAD and LTE. Caution should be taken during interpretation given the small sample size and use of external controls in the LTE."

Clinical • Clinical data • Late-breaking abstract • P1 data • Alzheimer's Disease • CNS Disorders • Pain • MAPT

Exploratory Tau Biomarker Results From a Multiple Ascending-Dose Study of BIIB080 in Alzheimer Disease: A Randomized Clinical Trial. (PubMed, JAMA Neurol) - P1/2 | "Effects of BIIB080 on biomarkers and clinical outcomes are being further evaluated in a phase 2 trial. ClinicalTrials.gov Identifier: NCT03186989."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • CSF P-tau • CSF T-tau • MAPT • p-tau181

New Data from Biogen’s Investigational Antisense Oligonucleotide (ASO) Targeting Tau Shows Promise for Potential New Generation of Treatments in Early Alzheimer’s Disease (GlobeNewswire) - P1b | N=NA | "Biogen Inc...reported new Phase 1b clinical data from the study of BIIB080, an investigational antisense oligonucleotide (ASO) therapy targeting tau, in mild Alzheimer’s disease (AD). The data showed favorable trends on multiple exploratory endpoints of cognition and activities of daily living in AD (n=46), building upon prior results which showed a reduction of tau protein in the cerebral spinal fluid (CSF t-tau) and tau positron emission tomography (PET) across brain regions....Treatment was generally well tolerated throughout the study. The majority of adverse events were mild or moderate in severity, of which the most common were headache, back pain, pain in extremity, post-lumbar puncture syndrome and procedural pain."

P1 data • Alzheimer's Disease • CNS Disorders

Design of a Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Safety, and Tolerability of BIIB080 in Subjects with Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease Dementia (AAIC 2023) - P1/2, P2 | "The ongoing Ph2 CELIA trial will assess the efficacy, safety and tolerability of BIIB080, compared to placebo in subjects with MCI due to Alzheimer’s disease or mild Alzheimer’s disease dementia."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • MAPT

The development of peptide- and oligonucleotide-based drugs to prevent the formation of abnormal tau in tauopathies. (PubMed, Expert Opin Drug Discov) - "A Phase II trial of BIIB080 is ongoing in mild AD. Neurotrophic and neurogenic peptide mimetic compounds have also shown potential as treatment options for AD and other tauopathies."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

Biogen Successfully Targets Tau in Phase Ib Alzheimer's Study (BioSpace) - "Biogen presented data Wednesday for an Alzheimer’s disease therapy with a different target at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2023) in Stockholm, Sweden. In a Phase Ib study, Biogen’s BIIB080 successfully reduced tau pathology in patients with early-stage AD, measured by PET scan, across all six brain regions analyzed....Biogen is recruiting for a Phase II trial to confirm BIIB080’s safety, tolerability and efficacy in patients with mild and moderate AD. Biogen is targeting a Phase II completion date in December 2026."

P1 data • Trial status • Alzheimer's Disease • CNS Disorders