bepranemab (UCB0107) / UCB, Roche - LARVOL DELTA

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)

UCB managed 2022 headwinds and is ready for 2023 launches (UCB Press Release) - “Bepranemab…The efficacy, safety and tolerability of bepranemab in patients with early AD are investigated in a Phase 2 study, which started in Q2 2021. Recruitment for this study was completed ahead of time and topline results are now expected earlier, in Q4 2024. UCB0599…Under a global co-development and co-commercialization agreement with Novartis, UCB is conducting a phase 2a study with UCB0599 for study participants with early-stage PD. In 2022, an additional dosing arm was introduced into the study. Recruitment is complete and topline results are now expected in Q4 2024.”

P2 data • P2a data • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

UPDATE ON THE TOGETHER STUDY: A PATIENTAND INVESTIGATOR-BLIND, RANDOMIZED, PLACEBOCONTROLLED STUDY EVALUATING THE EFFICACY, SAFETY AND TOLERABILITY OF BEPRANEMAB, UCB0107, IN PRODROMAL-TO-MILD ALZHEIMER’S DISEASE. (CTAD 2022) - P2 | "This proof-of-concept study employs clinical outcome measures, imaging, pharmacokinetics, and biomarkers to assess the ability of bepranemab to slow progression of AD when administered in the early stages of disease. Enrollment and randomization of participants are well on the way, with over half of the study centers active."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • CSF P-tau

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=421 | Active, not recruiting | Sponsor: UCB Biopharma SRL | Recruiting ➔ Active, not recruiting

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

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=450 | Recruiting | Sponsor: UCB Biopharma SRL | Trial completion date: Nov 2025 ➔ Jul 2025 | Trial primary completion date: Jul 2024 ➔ Apr 2024

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

Update on the TOGETHER study: a patient- and investigator-blind, randomized, placebo-controlled study evaluating the efficacy, safety and tolerability of bepranemab, UCB0107, in prodromal-to-mild Alzheimer’s disease (AAIC 2022) - No abstract available

Clinical • 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) - P1b; N=25; Completed; Sponsor: UCB Biopharma SRL; Active, not recruiting ➔ Completed; Trial completion date: Apr 2022 ➔ Nov 2021

Clinical • Trial completion • Trial completion date • 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; Enrolling by invitation ➔ Active, not recruiting

Clinical • Enrollment closed • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

[VIRTUAL] Design of a patient- and investigator-blind, randomized, placebo-controlled study to evaluate efficacy, safety, and tolerability of bepranemab, UCB0107, in prodromal to mild Alzheimer’s disease: The TOGETHER Study, AH0003 (AAIC 2021) - P2 | "TOGETHER is a proof-of-concept study that will employ clinical outcome measures, imaging, PK, biomarkers, and safety to assess the ability of bepranemab to slow the progression of AD when administered in the prodromal/mild stages of disease."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • CSF P-tau • Tau PET