ABvac40 / Grifols - LARVOL DELTA

IMPACT OF ABVAC40, AN ANTI-AΒ40 VACCINE, ON CAA PATHOLOGY: A COMPREHENSIVE RE-EVALUATION OF MRI FINDINGS FROM THE AB1601 PHASE 2 STUDY (ADPD 2025) - P2 | "Aims To evaluate the potential impact of ABvac40 on CAA pathology through a comprehensive re-assessment of CAA-related MRI variables in patients from the AB1601 study...Additionally, enhancing CAA management could potentially reduce ARIA risk associated with passive immunotherapies. Further investigation is warranted to confirm these Results ."

P2 data • Cerebral Hemorrhage • Hematological Disorders • Subarachnoid Hemorrhage

Vaccines for Alzheimer's disease: a brief scoping review. (PubMed, Neurol Sci) - "Although AD vaccines show promise in preclinical settings, longer and more comprehensive clinical trials are necessary to determine their long-term efficacy and safety. Standardized protocols and efforts to reduce regional disparities in research would facilitate better comparability and generalizability of findings, thereby guiding the future development of effective immunotherapies for Alzheimer's disease."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Psychiatry

Comprehensive analysis of phase 2 trial results and post-hoc findings of ABvac40, an anti-Aβ40 vaccine (CTAD 2024) - No abstract available

P2 data • Retrospective data

SAFETY AND TOLERABILITY OF ABVAC40, AN ANTI-AΒ40 VACCINE, IN THE CROSS-OVER EXTENSION OF THE AB1601 PHASE 2 STUDY (ADPD 2024) - P2 | "The cross-over extension phase 2 study has confirmed the safety profile of ABvac40 observed in Part-A. In addition, it demonstrates long-term tolerability, supporting ABvac40 potential as a therapeutic option for early-stage AD patients."

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

Plasma and cerebrospinal fluid proteomic association during Alzheimer's disease (AD) progression suggests possible new targets for treating AD patients (CTAD 2023) - " Paired plasma and CSF samples from three AD populations: AMBAR (Alzheimer’s Management by Albumin Replacement, phase IIb/III, treated with Plasma exchange with Albumin replacement—PE-Alb, n=134), ABvac40 (phase II, treated with a vaccine against amyloid-beta 40, n=92), Emory-AD (n=17), and one HC population (Emory-HC, n=18) were included in this analysis... Our analyses identified 70 proteoforms with median-to-high plasma-CSF correlations and these correlations were increased in AD patients compared to HC. We also observed that PE-Alb treatment decreased these correlations to the levels closer to those observed in HC. These findings emphasize the important role of plasma-CSF proteomic crosstalk during early AD progression and suggest possible new targets for AD therapy."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

ABvac40 induces anti-Aβx-40 plasma specific antibodies that bind with Aβ vascular deposits in brain slices from humans with cerebal amyloid angiopathy (CTAD 2023) - P2 | "This study demonstrates the specificity of plasma antibodies triggered by ABvac40, which recognize the C-terminal region of Aβx-40 peptides in different aggregated states (monomeric, oligomeric, and brain deposits). Binding of ABvac40-elicited antibodies to vascular and parenchymal amyloid brain deposits could have an important role in the mechanism of action of ABvac40. We hypothesize that the interaction of anti-Aβ40 antibodies with vascular amyloid could lead to a reduction of amyloid deposition in cerebral vessels."

Alzheimer's Disease • CNS Disorders • Targeted Protein Degradation • Aβ42

Safety, immunogenicity, clinical efficacy and biomarkers of ABvac40, an active vaccine anti-Aβ40 in patients with amnestic mild cognitive impairment or very mild Alzheimer's disease: final results of a phase 2 randomized study (CTAD 2023) - P2 | "The phase-2 trial of ABvac40 has shown positive results with a favorable safety profile, robust immunogenicity, and potential cognitive benefits for a-MCI and vm-AD patients. While additional research is warranted, these findings present ABvac40 as a promising candidate for early AD treatment."

Biomarker • Clinical • Late-breaking abstract • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Araclon Biotech Presents Positive Final Results from Phase 2 Clinical Study of ABvac40 Alzheimer’s Vaccine at CTAD (GlobeNewswire) - P2 | N=134 | NCT03461276 | Sponsor: Araclon Biotech S.L. | "Araclon gave a late-breaking presentation at the 2023 Clinical Trials on Alzheimer's Disease (CTAD) conference. Results show that ABvac40 had a favorable safety profile, elicited a robust immune response against Aβ40, and demonstrated some potential cognitive benefits in early-stage AD patients, meeting primary endpoints and showing differences between the vaccine- and placebo-treated groups in some secondary exploratory endpoints. Data confirm preliminary findings indicating a comparable safety profile between ABvac40 and placebo groups, with similar rates of treatment-emergent adverse events."

Late-breaking abstract • P2 data • Alzheimer's Disease

Safety and Immunogenicity of Repeated Doses of ABvac40 in Patients With a-MCI or Vm-AD (clinicaltrials.gov) - P2 | N=134 | Completed | Sponsor: Araclon Biotech S.L. | Active, not recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Mar 2023 | Trial primary completion date: Dec 2021 ➔ Mar 2023

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

AB1601 Phase 2 Study of ABvac40, an Anti-Aβ40 Vaccine: Safety and Immunogenicity of a Cross-Over Extension (AAIC 2023) - P2 | "The cross-over extension of the AB1601 Phase 2 study confirmed the excellent safety and tolerability profile of ABvac40, making this vaccine a potential candidate to be combined with other disease-modifying therapies. Results on immunogenicity supported those obtained in Part A, demonstrating that ABvac40 elicited a strong, specific, sustained and boostable immune response. This could have important implications for long-term treatments, especially in the context of preventive approaches."

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

ABVAC40 ELICITS A PREDOMINANTLY TH2 IMMUNE RESPONSE THAT SUPPORTS ITS EXCELLENT SAFETY PROFILE. (CTAD 2022) - "AN1792, the first Alzheimer´s disease (AD) vaccine entered clinical trials, was terminated due to meningoencephalitis attributed to a cellmediated immflamatory response (1, 2). ABvac40 drug substance induces a Th2 polarized T-helper immune response that promotes a humoral response and minimizes a proinflammatory effect, which is consistent with the excellent safety profile shown by ABvac40 in phase I and phase II studies."

Clinical • Alzheimer's Disease • CNS Disorders • Inflammation • Targeted Protein Degradation • APP • IFNG • IL4

AB1601 topline results – Phase 2 study of ABvac40 in patients with amnestic mild cognitive impairment (a-MCI) or very mild Alzheimer’s Disease (Vm-AD). (AAIC 2022) - No abstract available

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

UPDATE PHASE 2 STUDY OF ABVAC40, AN ACTIVE VACCINE ANTI-AΒ40 IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT OR VERY-MILD ALZHEIMER'S DISEASE (ADPD 2022) - P2 | "Part A was completed as previously planned and Part B is progressing as scheduled. Safety profile of ABvac40 and cross-over design will be presented in the congress. Top line results are expected for Q1-2022."

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

Safety and Immunogenicity of Repeated Doses of ABvac40 in Patients With a-MCI or Vm-AD (clinicaltrials.gov) - P2; N=120; Recruiting; Sponsor: Araclon Biotech S.L.; Trial completion date: Feb 2021 ➔ Feb 2022; Trial primary completion date: Feb 2021 ➔ Feb 2022

Clinical • IO biomarker • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • CD27 • CD4 • CD8 • IL10 • IL13 • IL15 • IL2 • IL2RA • IL4 • IL5 • IL6 • MRI • TNFA

Safety and Immunogenicity of Repeated Doses of ABvac40 in Patients With a-MCI or Vm-AD (clinicaltrials.gov) - P2; N=120; Recruiting; Sponsor: Araclon Biotech S.L.

Clinical • IO biomarker • New P2 trial • Alzheimer's Disease • Cognitive Disorders • CD27 • CD4 • CD8 • IL10 • IL13 • IL15 • IL2 • IL2RA • IL4 • IL5 • IL6 • MRI • TNFA

Safety and Immunogenicity of Repeated Doses of ABvac40 in Patients With a-MCI or Vm-AD (clinicaltrials.gov) - P2; N=120; Active, not recruiting; Sponsor: Araclon Biotech S.L.; Recruiting ➔ Active, not recruiting; Trial completion date: Feb 2022 ➔ Dec 2022

Clinical • Enrollment closed • IO biomarker • Trial completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • CD27 • CD4 • CD8 • IL10 • IL13 • IL15 • IL2 • IL2RA • IL4 • IL5 • IL6 • MRI • TNFA