ACI-24 / AC Immune - LARVOL DELTA

AC Immune reports full-year 2019 financial results and provides 2020 R&D outlook (GlobeNewswire) - "Initiation of a second Phase 2 trial of semorinemab in patients with moderate AD, by our collaboration partner Genentech, a member of the Roche Group. This antibody is also being studied in a separate Phase 2 trial in prodromal to mild AD; Presented initial interim data from an on-going Phase 1b trial of the ACI-24 anti-Abeta vaccine to treat Down syndrome (DS)-related AD...2020 Clinical Readouts: Semorinemab, anti-Tau antibody: Phase 2 trial primary completion (estimated last patient, last visit) in prodromal/mild in Q2; ACI-24 anti-Abeta vaccine in DS: Phase 1b full study reporting in H2; ACI-24 in AD: Phase 2, 12-month interim analysis in H2."

New P2 trial • P1 data • P2 data • Trial primary completion date • Trial status • Alzheimer's Disease • CNS Disorders

Prediction of the 3D conformation of a small peptide vaccine targeting Aβ42 oligomers. (PubMed, Phys Chem Chem Phys) - "Using the same scheme, we predicted the 3D conformation of the optimized ACI-24 peptide vaccine, an Aβ peptide with the first 15 residues of Aβ42 (Aβ1-15)...Additionally, residues (D1, D7, S8, H13, and Q15) were identified as the key residues of the vaccine to contact either of the two Aβ oligomers. This work provides a feasible implementation scheme of immunoinformatic and MD simulations for the development of AD small peptide vaccines, validating the power of the scheme as a parallel tool to the experimental approaches and injecting molecular-level information into the understanding and design of anti-AD vaccines."

Journal • Alzheimer's Disease • CNS Disorders • Aβ42

ANTI-ABETA LIPOSOMAL VACCINE, ACI-24.060, RETAINS MEMORY IN AN AGGRESSIVE MOUSE MODEL OF ALZHEIMER'S DISEASE (ADPD 2024) - "The widely used 5xFAD mice that reportedly recapitulates many AD-related phenotypes including amyloid plaques, neuron loss and pronounced amyloidosis, displayed severe cognitive decline before 11 months of age. Treatment with the Abeta targeting vaccine, ACI-24.060, maintained both learning and memory capabilities to the levels of non-diseased animals. These neurological functional results are consistent with the accumulating immunohistochemical data on the activity of ACI-24.060 and strongly support its continued clinical development."

Preclinical • Alzheimer's Disease • Amyloidosis • CNS Disorders

The Down Syndrome – Clinical Global Impression of Change (DS-CGIC) (CTAD 2023) - "In the context of a multicentre study of an anti-amyloid vaccine, ACI-24 (the ABATE study part 2 (participants with DS)) a semistructured interview for use with the caregiver of participants with DS has been developed, the DS-CGIC... The changes over time on the DS-CGIC will be examined as an exploratory measure both on placebo and active treatment. Comparison of the changes over time with those on other instruments will help to establish the validity of the scale, as will its use in natural history studies such as the Trial Ready Cohort – Down syndrome (TRC-DS)."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Developmental Disorders • Genetic Disorders

Anti-Abeta liposomal vaccine, ACI-24.060, induces anti-Abeta antibodies with binding profiles mirroring clinically validated monoclonal antibodies (CTAD 2023) - "In NHP, a liposomal anti-Abeta vaccine, ACI-24.060 induced antibody responses with strong binding to pathological Abeta oligomers and pyroglutamate-Abeta species. Importantly, the preference in binding of the polyclonal antibodies to oligomeric versus monomeric Abeta mirrored that of lecanemab, with a similar 3 log differential. Binding of the polyclonal antibodies to pyroglutamate-Abeta was in the range of binding of clinically relevant concentrations of donanemab."

Clinical • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Genetic Disorders

Alzheimer’s vaccine granted Fast Track designation (European Pharmaceutical Review) - "The 'potential safety, efficacy, and logistical advantages of a vaccine over monoclonal antibodies strongly support the development of therapeutics such as ACI-24.060 as the next generation of anti-Abeta therapies,' Dr Michael Rafii...and the Principal Investigator of the trial noted."

Media quote • Regulatory

4. An innovative clinical trial designed to evaluate the effects of ACI-24.060 in Alzheimer's Disease and in Down syndrome (ABATE Study) (AAIC 2023) - P1b/2 | "The field of biomarker-based translational medicine has been mobilized by the clinical evaluation of targeting of toxic abeta fragments and aggregates in monoclonal antibody trials. As shown we are utilizing these advances in an innovative clinical trial design for an efficient, evidence-based translational medicine approach to test ACI-24.060 as a novel Abeta vaccine candidate. This approach allows the parallel investigation of ACI-24.060 for the treatment and prevention of both sporadic AD and DSAD."

Clinical • IO biomarker • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Genetic Disorders

AC Immune at AD/PD 2023 to Present New Clinical and Preclinical Data from its Precision Medicine Pipeline (GlobeNewswire) - “AC Immune SA…announced that ten presentations will be delivered at the International Conference on Alzheimer’s & Parkinson’s Diseases (AD/PDTM 2023), taking place in Gothenburg, Sweden, and virtually, on March 28 – April 1, 2023. In addition, Johannes Streffer, M.D., Chief Medical Officer of AC Immune, will join an expert panel to discuss the latest developments in immunotherapies in Alzheimer’s disease. Andrea Pfeifer, Ph.D., CEO of AC Immune SA, commented: ‘The ten presentations during this AD/PDTM conference demonstrate AC Immune’s progress towards our over-arching goal, which is to shift the treatment paradigm towards Precision Medicine and disease prevention. As our clinical programs in Alzheimer’s and Parkinson’s diseases are advancing, we are solidifying our position as a leading developer of vaccines for neurodegenerative diseases.’”

Biomarker • Clinical • Preclinical • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Parkinson's Disease

BENEFICIAL EFFECT OF ACI-24 VACCINATION ON ABETA PLAQUE PATHOLOGY AND MICROGLIAL PHENOTYPES IN AN AMYLOIDOSIS MOUSE MODEL (ADPD 2023) - "Accordingly, plaque-distant microglia displayed a more ramified morphology, supporting beneficial effects of the vaccination on bulk microglial phenotypes. Conclusions This study demonstrates that administration of the Abeta targeting vaccine, ACI-24, triggers protective microglial responses that translate into a reduction of AD pathology highlighting its use as a safe and cost effective AD therapeutic intervention."

IO biomarker • Preclinical • Alzheimer's Disease • Amyloidosis • CNS Disorders • APOE

ABATE STUDY – UTILIZING BIOMARKER-BASED DEVELOPMENT FOR OPTIMIZED ACI-24, A NOVEL CANDIDATE VACCINE FOR THE TREATMENT AND PREVENTION OF ALZHEIMER'S DISEASE (ADPD 2023) - "Conclusions The field of biomarker-based translational medicine has been mobilized by the recent understanding of how to clinically evaluate targeting of toxic Abeta fragments and aggregates in trials using monoclonal antibodies. We demonstrate here how we will utilize these advances in an innovative clinical trial design for an efficient, evidence-based translational medicine approach to test optimized ACI-24 as a novel Abeta vaccine candidate and present initial clinical data."

Biomarker • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Genetic Disorders

Beneficial Effect of ACI-24 Vaccination on Aβ Plaque Pathology and Microglial Phenotypes in an Amyloidosis Mouse Model. (PubMed, Cells) - "Accordingly, bulk transcriptomic analysis revealed a trend towards the reduced expression of several disease-associated microglia (DAM) signatures that is in line with the reduced Aβ plaque load triggered by ACI-24 vaccination. Our study demonstrates that administration of the Aβ targeting vaccine ACI-24 reduces AD pathology, suggesting its use as a safe and cost-effective AD therapeutic intervention."

IO biomarker • Journal • Preclinical • Alzheimer's Disease • Amyloidosis • CNS Disorders • APOE • NLRP3

Advantages of next generation SupraAntigen® platform liposomal vaccines to immunize against pathological targets of Alzheimer’s disease (CTAD 2022) - " For Abeta, several vaccines were generated as follows: a liposome-based SupraAntigen® vaccine (i.e., optimized ACI-24) containing the antigenic peptide Abeta 1-15, an adjuvant and a universal T-helper cell peptide; and CRM-conjugated vaccines containing various antigenic Abeta peptides (e.g., ACC-001) or full-length Abeta (i.e., AN1792) mixed with adjuvant...This was in line with the epitope mapping data, which demonstrated strong binding to the phosphorylated residues for the ACI-35.030-induced antibodies... For both Abeta and Tau targeting vaccines, the liposome-based SupraAntigen® vaccines demonstrated a superior quality of the IgG repertoire generated post-immunization. The responses in NHPs were well tolerated, homogenous, robust and boostable over time, while broadly engaging relevant pathological epitopes. For Abeta, the liposome-based SupraAntigen® vaccine generated the highest titers of antibodies specifically targeting pyroGlu-Abeta."

Alzheimer's Disease • CNS Disorders

Optimized ACI-24, an amyloid beta (Abeta) vaccine that safely drives immunity to oligomers and Pyroglutamate Abeta, key pathological species of Alzheimer’s disease (AD) (AAIC 2022) - No abstract available

Alzheimer's Disease • CNS Disorders

Biomarker-based development for optimized ACI-24, a novel candidate vaccine for the treatment and prevention of Alzheimer’s disease (AAIC 2022) - No abstract available

Biomarker • Alzheimer's Disease • CNS Disorders

Safety, Tolerability, and Immunogenicity of the ACI-24 Vaccine in Adults With Down Syndrome: A Phase 1b Randomized Clinical Trial. (PubMed, JAMA Neurol) - P1 | "These results support progression to clinical trials using an optimized formulation of the ACI-24 vaccine among individuals with DS. ClinicalTrials.gov Identifier: NCT02738450."

Clinical • Journal • P1 data • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Developmental Disorders • Genetic Disorders • Hematological Disorders • Immunology • Inflammation • APP

An amyloid beta vaccine that safely drives immunity to a key pathological species in Alzheimer's disease: pyroglutamate amyloid beta. (PubMed, Brain Commun) - "These data are in striking contrast to results obtained with other clinically tested Abeta targeting vaccines which generated restricted and limited antibody diversity. Taken together, our findings demonstrate that optimized ACI-24 vaccination represents a breakthrough to provide a safe immune response with a broader Abeta sequence recognition compared to previously tested vaccines, creating binders to pathogenic forms of Abeta important in pathogenesis including pGlu-Abeta3-42."

Journal • Alzheimer's Disease • CNS Disorders

AC Immune Reports Full Year 2021 Financial Results and Provides Corporate Update (Yahoo Finance) - “2022 Clinical Milestones: ACI-24 (optimized) anti-Abeta vaccine: ACI-24 (optimized vaccine formulation) Phase 1b/2a First-Patient-In (AD) in H1 Phase 1b in AD readout and decision to move into DS in H2; Crenezumab anti-Abeta antibody: Top line Phase 2 results from AD prevention trial in patients with autosomal dominant AD in H1; Semorinemab anti-Tau antibody: Additional fluid biomarker data from the Phase 2 Lauriet study in mild-to-moderate AD in H2; PI-2620 Tau-PET tracer: Phase 2 and Phase 1 results in AD and progressive supranuclear palsy (PSP) respectively, in H2.”

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

AN OPTIMIZED AMYLOID BETA (ABETA) VACCINE THAT SAFELY DRIVES IMMUNITY TO THE KEY PATHOLOGICAL SPECIES OF ALZHEIMER’S DISEASE (AD) (ADPD 2022) - "This unique binding profile, including pyroGlu-Abeta3-42 and oligomers combines the targets of mAbs (aducanumab, donanemab) and the potential of enhancing plaque reduction. These data support fast progression of optimized ACI-24 into clinics as a disease modifying treatment for AD-DS and AD."

Alzheimer's Disease • CNS Disorders • Developmental Disorders • Genetic Disorders

AC Immune ACI-24 Data in Brain Communications Show Abeta Vaccine-Candidate Induces Immunity Against pyroGlu-Abeta, Key Driver of Alzheimer’s Disease (GlobeNewswire) - “AC Immune SA…announced that preclinical data on the optimized formulation of its wholly-owned amyloid-beta (Abeta) vaccine program, ACI-24, were published in the peer reviewed journal Brain Communications. Based on these and other preclinical data, as well as the results of three clinical trials with ACI-24, AC Immune plans to advance clinical development of the optimized formulation to the next stage for both Alzheimer’s disease (AD) and Down syndrome (DS) related AD in 2022.”

New trial • Preclinical • Alzheimer's Disease • CNS Disorders

[VIRTUAL] ACI-24, an anti-beta amyloid vaccine, in patients with mild Alzheimer’s disease: Results of a phase 2, randomized, double-blind, placebo-controlled study (CTAD 2021) - "Treatment with the anti-Aβ vaccine ACI-24 was safe and well tolerated in mild AD patients in the phase 2 study. Initial evidence of a pharmacodynamic effect of ACI-24 suggesting target engagement was observed. Overall, these results support the ongoing development of optimized vaccine formulation of ACI-24 in patients with AD."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Dementia • Immunology • Inflammation • Mental Retardation • Pain • MRI

New Data on AC Immune’s Abeta and pTau Clinical Programs in Alzheimer’s Disease To Be Presented at CTAD 2021 (GlobeNewswire) - “AC Immune SA…announces that new data on its investigational Alzheimer’s disease (AD) candidates semorinemab, ACI-35.030 and ACI-24 will be featured in the scientific program of the Clinical Trials on Alzheimer’s Disease (C-TAD) Conference, taking place virtually and in person in Boston, on November 9-12, 2021.”

Clinical data • Alzheimer's Disease • CNS Disorders

A Study of ACI-24 in Adults With Down Syndrome (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: AC Immune SA; N=72 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Developmental Disorders • Genetic Disorders • Amyloid PET • MRI • Tau PET

[VIRTUAL] ACI-24 in Adults with Down syndrome: Results of a phase 1b, randomized, placebo-controlled study (AAIC 2021) - "ACI-24 was safe and well-tolerated in adults with DS. Evidence of immunogenicity was observed with this T-cell independent vaccine along with pharmacodynamic and target engagement effects as measured by an increase in plasma Aβ 1-40 and Aβ 1-42 levels in treated groups as compared to placebo. These results support the pursuance of an accelerated clinical development with an optimized formulation of ACI-24."

Clinical • P1 data • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Genetic Disorders • Immunology • Inflammation • MRI

AC Immune Presents Full Phase 1b Results on Anti-Abeta Vaccine and Discusses its First-in-Class Diagnostic for Parkinson’s Disease at AAIC 2021 (GlobeNewswire) - "Full Phase 1b results support the continued clinical development of anti-Abeta vaccine approaches in DS-related Alzheimer’s disease (AD); AC Immune...outlined two presentations being delivered at the Alzheimer’s Association International Conference (AAIC) 2021, taking place both in Denver, USA and virtually from July 26-30, 2021...AC Immune is also presenting a poster on ACI-12589, a first-in-class positron emission tomography (PET) imaging tracer targeting a-syn that is being developed as a first-in-class diagnostic for Parkinson’s disease (PD)."

Biomarker • Clinical data • P1 data • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

AC Immune Provides Update on Alzheimer’s Disease Vaccine Candidates Targeting Pathological Amyloid-Beta (GlobeNewswire) - "We believe the optimized ACI-24 formulation represents a potential breakthrough in Abeta vaccination...suggested key culprits in the Abeta pathway driving early Alzheimer’s disease....We are planning to file an Investigational New Drug (IND) application for the optimized ACI-24 formulation by year-end, followed by an accelerated clinical development in Down syndrome-related AD, with start of Phase 2 as early as 2022/23....AC Immune will complete the Phase 2 study with the 24-month analysis on the basis of currently enrolled patients."

IND • New P2 trial • Alzheimer's Disease • CNS Disorders