bepranemab (UCB0107) / UCB, Roche - LARVOL DELTA

LONG-TERM SAFETY OF BEPRANEMAB: DATA FROM PHASE II/IB OPEN-LABEL EXTENSION STUDIES IN PRODROMAL–MILD ALZHEIMER'S DISEASE AND PROGRESSIVE SUPRANUCLEAR PALSY (ADPD 2026) - P1, P2 | "Results from the TOGETHER and PSP002 OLEs will provide further information about the long-term safety of bepranemab."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

Safety, tolerability and biomarker results of bepranemab in participants with progressive supranuclear palsy: a randomised, multicentre, double-blind, placebo-controlled, phase 1b trial. (PubMed, BMJ Neurol Open) - P1 | "Multiple doses of bepranemab 90 mg/kg were well tolerated with an acceptable safety profile in participants with PSP. High target occupancy was observed."

Biomarker • Journal • P1 data • Alzheimer's Disease • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

Drug Development. (PubMed, Alzheimers Dement) - P2 | "Exposure-response modeling and simulation of TOGETHER study data confirmed improvement in clinical outcomes with bepranemab in a prodromal-mild AD population with low tau burden or APOε4 non-carriers. The modeling also predicted that higher bepranemab doses are likely to be therapeutically beneficial (vs placebo) in future clinical trials."

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

Drug Development. (PubMed, Alzheimers Dement) - P2 | "TOGETHER provides the first clinical demonstration of slowing of tau accumulation with an antibody targeting the tau mid-region, as evidenced by tau PET imaging, and marks the first time that any tau-directed therapy has demonstrated a clinical benefit."

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

Results from the open-label extension period of TOGETHER, a Phase II study evaluating efficacy, safety and tolerability of bepranemab in prodromal–mild Alzheimer's disease (CTAD 2025) - No abstract available

Clinical • P2 data • Alzheimer's Disease • CNS Disorders

TOGETHER: A Study to Test the Efficacy, Safety, and Tolerability of Bepranemab (UCB0107) in Patients With Mild Cognitive Impairment or Mild Alzheimer's Disease (AD) (clinicaltrials.gov) - P2 | N=466 | Completed | Sponsor: UCB Biopharma SRL | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • CSF P-tau • p-tau181

A Study to Test the Safety and Tolerability of Long-term UCB0107 Administration in Study Participants With Progressive Supranuclear Palsy (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: UCB Biopharma SRL | Trial completion date: Mar 2027 ➔ Dec 2027 | Trial primary completion date: Mar 2027 ➔ Dec 2027

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

Anti-Tau Agent Bepranemab Slows Tau Accumulation in Phase 2 TOGETHER Trial (NeurologyLive) - P2 | N=466 | TOGETHER (NCT04867616) | Sponsor: UCB Biopharma SRL | "In the phase 2 TOGETHER trial (NCT04867616), treatment with UCB’s bepranemab, an investigational monoclonal antibody targeting tau protein, led to slowing of tau accumulation in the tau mid-region in patients with prodromal to mild Alzheimer disease (AD). According to the study authors, this was the first clinical demonstration of such slowing, and marked the first time any tau-directed therapy has demonstrated a clinical benefit...Presented at the 2025 Alzheimer’s Association International Conference....In the latest AAIC data, bepranemab-treated patients had slowed tau accumulation in whole cortical gray (n = scanned/total: 90 mg/kg bepranemab [113 of 152]; 45 mg/kg bepranemab [104 of 152]; and placebo [97 of 156]) and jack temporal meta regions (90 mg/kg bepranemab [114 of 152]; 45 mg/kg bepranemab [105 of 152]; and placebo [97 of 156]) at week 80."

P2 data • Alzheimer's Disease

SAFETY MRI AND VOLUMETRIC MRI RESULTS FROM TOGETHER, A DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE II STUDY OF BEPRANEMAB IN PRODROMAL-MILD AD (ADPD 2025) - P2 | "Conclusions In TOGETHER, the postbaseline incidence of new MRI abnormalities was very low. There were no neuroimaging concerns; haemorrhagic and inflammatory findings were similar between groups."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders

PHASE II STUDY OF BEPRANEMAB IN PEOPLE WITH PRODROMAL-MILD ALZHEIMER'S DISEASE (AD): POPULATION SUBGROUP ANALYSIS (ADPD 2025) - P2 | "Conclusions TOGETHER is the first study to provide evidence for clinical efficacy of anti-tau therapy in AD, with significant reductions in tau accumulation and cognitive decline versus placebo. Predefined subgroup data were informative and drove the decision to conduct the post hoc analyses."

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

Drug Development. (PubMed, Alzheimers Dement) - "The pool of CSF tau species included a subset of tau MTBR-containing fragments recovered by bepranemab. A minor fraction of these fragments had domains overlapping with the upstream domain constituting the AD tau aggregate core. These fragments increased over DIAD stages. Our study supports bepranemab engagement against a specific pool of tau species in CSF. This work was sponsored by UCB."

Journal • Alzheimer's Disease • CNS Disorders

UCB Presents Encouraging Data on Bepranemab in Early Alzheimer’s Disease in Phase 2a Study at CTAD 2024 (UCB Press Release) - P2a | N=466 | TOGETHER (NCT04867616) | Sponsor: UCB Biopharma SRL | "In the overall study population, no beneficial effect of low- or high-dose bepranemab compared with placebo was observed on the primary endpoint...Slowed the rate of tau accumulation versus placebo in key brain regions by 33%-58%. Slowed cognitive decline by 21-25% versus placebo - the change between Baseline and Week 80 in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) total score...In two predefined subgroups, low tau burden at Baseline and APOε4* non-carriers, treatment benefits were observed across multiple outcome measures...Slowed the rate of tau accumulation versus placebo in key brain regions by 63%-67% at Week 80. Slowed clinical disease progression by 29% - as measured by the change in CDR-SB between Baseline and Week 80. Slowed disease progression according to secondary/exploratory endpoints, including measures of Activities of Daily Living by 41-54% at Week 80."

P2a data • Alzheimer's Disease • CNS Disorders

Synthetic receptors for programmable tau-responsive cellular therapies (Neuroscience 2024) - "Receptors with recognition domains derived from clinical anti-tau mAbs (semorinemab, gosuranemab, bepranemab) were built and expressed in mouse mesenchymal stromal cells (mMSCs) (Fig 1A; synNotch constructs displayed). We envision tau receptors being used in a cell-based therapy, outfitting microglia and astrocytes with novel therapeutic behaviors. In neurons, tau receptors may serve as useful tools for reporting the extent of local tau pathology in real-time."

Alzheimer's Disease • CNS Disorders • Dementia • BDNF

Identification and development of bepranemab, an antibody targeting the mid-region of tau (CTAD 2024) - No abstract available

Late-breaking abstract

Results from TOGETHER, a Phase II study of bepranemab in prodromal–mild AD (CTAD 2024) - No abstract available

Late-breaking abstract • P2 data

Bepranemab, the tau mid-region hypothesis, and future implications (CTAD 2024) - No abstract available

Late-breaking abstract

UCB Announces Bepranemab Phase 2a Study Results Accepted for Late-Breaking Presentation at Clinical Trials on Alzheimer’s Disease (CTAD) 2024 Meeting (UCB Press Release) - "UCB today announced that the results of its double-blind TOGETHER (AH0003) Phase 2a study of bepranemab - an investigational anti-tau antibody - in people living with prodromal to mild Alzheimer’s Disease (AD), have been accepted for presentation in a late-breaking symposium at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) Meeting....The presentation will highlight primary and key secondary results from the Phase 2a study, including clinical, safety, and imaging endpoints. This acceptance underscores UCB’s commitment to addressing the urgent need for new treatment options for Alzheimer's disease."

Late-breaking abstract • P2a data • Alzheimer's Disease

LATE BREAKING SYMPOSIUM 3: Results from TOGETHER, a double-blind, placebo-controlled Phase II study evaluating efficacy, safety and tolerability of bepranemab in prodromal–mild AD (CTAD 2024) - No abstract available

Clinical • Late-breaking abstract • P2 data

Roche, UCB Return Rights to Alzheimer's Treatment 'Bepranemab' [Google translation] (Medipana) - "Roche announced that it has decided to return all rights to bepranemab, an anti-tau protein antibody, for which it had signed a worldwide exclusive licensing agreement with UCB...This return of rights is drawing more attention as it comes ahead of the announcement of the phase 2a clinical results of bepranemab at the Alzheimer's Clinical Trials Symposium scheduled to be held in Madrid, Spain from the 29th. UCB stated that the clinical results were encouraging, but given that it returned the rights right before the announcement of the clinical results, it is interpreted that Roche was not satisfied with the results."

Licensing / partnership • Alzheimer's Disease • CNS Disorders

Characterization of cerebrospinal fluid tau MTBR species binding to Bepranemab (AAIC 2024) - "The pool of CSF tau species included a subset of tau MTBR-containing fragments recovered by bepranemab. A minor fraction of these fragments had domains overlapping with the upstream domain constituting the AD tau aggregate core. These fragments increased over DIAD stages."

Alzheimer's Disease • CNS Disorders

A Study to Test the Safety and Tolerability of UCB0107 in Study Participants With Progressive Supranuclear Palsy (PSP) (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: UCB Biopharma SRL | Phase classification: P1b ➔ P1

Phase classification • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

A Study to Test the Safety and Tolerability of Long-term UCB0107 Administration in Study Participants With Progressive Supranuclear Palsy (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: UCB Biopharma SRL | Trial completion date: Nov 2026 ➔ Mar 2027 | Trial primary completion date: Nov 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

Passive tau-based immunotherapy for tauopathies. (PubMed, Handb Clin Neurol) - "At present, 12 anti-tau antibodies have entered clinical trials, and 7 of them are still in clinical testing for primary tauopathies and AD (semorinemab, bepranemab, E2814, JNJ-63733657, Lu AF87908, PNT00, and APNmAb005). Two other anti-tau monoclonal antibodies have been discontinued for the treatment of primary tauopathies, i.e., gosuranemab and tilavonemab. Further evidence will come from ongoing Phase I/II trials on passive immunotherapeutics for treating primary and secondary tauopathies."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Frontotemporal Lobar Degeneration • Movement Disorders • Progressive Supranuclear Palsy

Clinical Development of Passive Tau-Based Immunotherapeutics for Treating Primary and Secondary Tauopathies. (PubMed, Expert Opin Investig Drugs) - "At present, 14 anti-tau antibodies have entered clinical trials, and 9 of them are still in clinical testing for progressive supranuclear palsy syndrome and AD (semorinemab, bepranemab, E2814, JNJ-63733657, Lu AF87908, APNmAb005, MK-2214, PNT00, and PRX005). The most advanced anti-tau monoclonal antibody for treating AD is semorinemab, while bepranemab is the only anti-tau monoclonal antibody still in clinical testing for treating progressive supranuclear palsy syndrome. Further evidence on passive immunotherapeutics for treating primary and secondary tauopathies will come from ongoing Phase I/II trials."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Frontotemporal Lobar Degeneration • Movement Disorders • Progressive Supranuclear Palsy

"Also bepranemab? https://t.co/nxo5TIBbj9" (@nvillain_alz)