sabirnetug IV (ACU193 IV) / Acumen Pharma - LARVOL DELTA

Acumen Pharmaceuticals Showcases pTau217 Trial Screening Progress in Phase 2 ALTITUDE-AD Trial and Preclinical Research Methods at AD/PD 2025 and AAN Annual Meeting (GlobeNewswire) - "Biomarker results from Phase 1 INTERCEPT-AD trial of sabirnetug in patients with early Alzheimer’s disease recently published in The Journal of Prevention of Alzheimer's Disease....Acumen Pharmaceuticals...presented extended results from its validated research-use plasma pTau217 assay to screen potential participants in the ongoing Phase 2 ALTITUDE-AD clinical trial of sabirnetug, showing this strategy has performed as intended....The company presented the results during an oral presentation at the International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders (AD/PD) in Vienna, Austria, from April 1-5, 2025, and will deliver an encore presentation at the American Academy of Neurology (AAN) Annual Meeting in San Diego, Calif., from April 5-9, 2025."

P1 data • P2 data • Preclinical • Alzheimer's Disease

PROTOCOL FOR THE PREPARATION OF STABLE MONOMERIC AMYLOID BETA (ADPD 2025) - "We compared published methods for production of pure, stable monomers and applie d resultant preparations to assays utilizing the A βO-selective antibody sabirnetug (ACU193), which is currently being tested in the phase 2 study ALTITUDE -AD... 10kDa filtration of A β1-40 enables production of pure monomeric A β solutions essential to assess selectivity of assays during development."

Clinical • Alzheimer's Disease • CNS Disorders

UTILITY OF HUMAN IPSC -DERIVED NEURONAL MODEL FOR EVALUATING SYNAPTIC BINDING OF AMYLOID ΒETA OLIGOMERS (ADPD 2025) - "We observed robust binding of A βOs to human iPSC -derived neurons, demonstrating competent synaptic binding sites, synapse -binding A βO in AD brain extract, and neutralization of A βO binding by sabirnetug, an immunotherapeutic currently being tested in the p hase 2 ALTITUDE -AD study."

IO biomarker • Alzheimer's Disease • CNS Disorders

COMPARISON OF BINDING SPECIFICITY OF ANTI -AMYLOID -BETA ANTIBODIES IN SERIAL SECTIONS OF APPNL-F/NL-F; APOE4 MOUSE BRAINS (ADPD 2025) - "Aims: Immunotherapy is the leading treatment strategy for Alzheimer's disease (AD), with the FDA approving anti-amyloid-beta (Aβ) monoclonal antibodies (mAbs), lecanemab and donanemab, for early -stage AD... Immunoreactivity of recombinant lecanemab (r -lecanemab), recombinant murine lecanemab precursor (r -mAb158), and sabirnetug (ACU193) mAbs was quantitatively characterized in serial sections from briefly fixed 20 -month-old APPNL -F/NL-F; ApoE4fl/fl mice... The observed differences in binding affinities suggest that antibody selectivity may play a role in ARIA prevalence. High -magnification analyses will further clarify these differences, potentially revealing whether antibodies linked to higher ARIA show increased binding to vascular amyloid and how binding profiles vary with concentration. Funding_1R01NS136122 -01_CAL."

Preclinical • Alzheimer's Disease • CNS Disorders

ALTITUDE-AD: USE OF PLASMA PTAU217 SCREENING IN AN ONGOING PHASE 2 STUDY OF SABIRNETUG FOR EARLY SYMPTOMATIC ALZHEIMER'S DISEASE (ADPD 2025) - P2 | "A more complete dataset will be presented. Conclusions The pTau217 enrichment strategy is performing as intended, reducing unnecessary amyloid PET scans or CSF procedures for potential trial participants as compared to INTERCEPT-AD, which did not use plasma pTau217 screening."

P2 data • Alzheimer's Disease • CNS Disorders • Aβ42 • CSF Aβ40 • CSF Aβ42

Acumen Pharmaceuticals Completes Enrollment of ALTITUDE-AD, a Phase 2 Clinical Trial of Sabirnetug (ACU193) in Early Alzheimer’s Disease (GlobeNewswire) - "Acumen Pharmaceuticals, Inc...today announced the completion of enrollment in its ALTITUDE-AD Phase 2 trial of sabirnetug (ACU193) in patients with early Alzheimer’s disease. Acumen completed enrollment ahead of schedule and plans to report topline results, including efficacy and safety data, in late 2026."

P2 data • Trial status • Alzheimer's Disease

Acumen Pharmaceuticals Announces Topline Results from Phase 1 Study of Subcutaneous Formulation of Sabirnetug in Healthy Volunteers (GlobeNewswire) - P1 | N=28 | NCT06511570 | Sponsor: Acumen Pharmaceuticals | "Acumen Pharmaceuticals, Inc...today announced topline results from its Phase 1 study comparing pharmacokinetics (PK) between subcutaneous (SC) and intravenous (IV) formulations of sabirnetug in healthy volunteers. Weekly SC administration of sabirnetug was well-tolerated with systemic exposure supporting further clinical development....The most frequently reported adverse events included injection site reactions (62.5%), all of which were mild (Grade 1) in severity and resolved. No other safety signals were identified."

P1 data • Alzheimer's Disease

Acumen Pharmaceuticals to Present During International Conference on Alzheimer’s and Parkinson’s Diseases 2025 and American Academy of Neurology Annual Meeting (GlobeNewswire) - "Acumen Pharmaceuticals, Inc...today announced upcoming scientific presentations at the International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders (AD/PD) in Vienna, Austria from April 1-5, 2025, and the American Academy of Neurology (AAN) Annual Meeting in San Diego, Calif., from April 5-9, 2025. Oral presentations will focus on implementation of a validated research-use plasma pTau217 assay in the clinical trial participant screening process. Poster presentations will focus on methods of interrogating the binding of AβOs to a model of human neurons; methods to more accurately assess the AβO selectivity of nonclinical assays and sabirnetug; and early effects of sabirnetug on synaptic biomarkers in AD."

P2 data • Preclinical • Alzheimer's Disease

INTERCEPT-AD Biomarker Results: Early Effect of Sabirnetug Treatment on Synaptic Biomarkers in Alzheimer's Disease (AAN 2025) - P1, P2 | "In INTERCEPT-AD, three administrations of sabirnetug were associated with lower CSF concentrations of pre- and post-synaptic AD-related proteins, consistent with sabirnetug nonclinical data demonstrating interruption of AβO synaptic binding. VAMP2 concentrations in the CSF appeared most sensitive to sabirnetug, lowering in all three MAD cohorts. Numeric decreases in neurogranin were also consistently observed."

Biomarker • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • VAMP2

ALTITUDE-AD: Use of a Validated Plasma pTau217 Assay to Screen Potential Participants in an Ongoing Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Sabirnetug for Early Alzheimer's Disease (AAN 2025) - P2 | "The pTau217 enrichment strategy is performing as intended, reducing unnecessary amyloid PET scans or LP procedures for potential trial participants compared to INTERCEPT-AD, which did not use plasma pTau217 screening."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Aβ42 • CSF Aβ42

Biofluid biomarker changes following treatment with sabirnetug (ACU193) in INTERCEPT-AD, a phase 1 trial in early Alzheimer's disease. (PubMed, J Prev Alzheimers Dis) - P1, P2 | "Following three sabirnetug doses, changes in CSF and plasma biomarkers were observed. The CSF biomarker response increased with increasing dose and exposure duration, consistent with previous reports that sabirnetug reaches the central compartment and engages its AβO target. The ongoing phase 2 ALTITUDE-AD study (NCT06335173) will test whether sabirnetug's pharmacodynamic effects can be substantiated with a larger sample size and longer treatment duration."

Biomarker • Journal • P1 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • CSF P-tau • GFAP • p-tau181 • VAMP2

INTERCEPT-AD, a phase 1 study of intravenous sabirnetug in participants with mild cognitive impairment or mild dementia due to Alzheimer's disease. (PubMed, J Prev Alzheimers Dis) - P2 | "The Phase 1 INTERCEPT-AD study provided safety, tolerability, dosing, and target engagement data that supported the design of the ongoing ALTITUDE-AD study (NCT06335173)."

Clinical • Journal • P1 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Dermatology • Hematological Disorders • Pain • APOE

Public Health. (PubMed, Alzheimers Dement) - "Certain factors of trial participation differed by participant gender, including motivations for participation and perceived burden of some study procedures."

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

Developing Topics. (PubMed, Alzheimers Dement) - P1 | "An ultra-sensitive CSF total sabirnetug immunoassay was successfully developed on the MSD S-PLEX platform. Assay qualification demonstrated sensitivity, accuracy and precision, selectivity, specificity, dilutional linearity, and stability of the method. Analysis of CSF samples collected during INTERCEPT-AD showed the method is applicable for quantification of total drug exposure of sabirnetug in clinical trials."

Journal • Alzheimer's Disease • CNS Disorders

Developing Topics. (PubMed, Alzheimers Dement) - P1 | "In INTERCEPT-AD, three administrations of sabirnetug lowered CSF levels of both pre- and post-synaptic proteins, consistent with sabirnetug's proposed mechanism of action to inhibit AβO synaptic binding. VAMP2 appeared most sensitive to sabirnetug in this study, lowering significantly in all three MAD cohorts; other markers previously reported to have a statistically significant response to sabirnetug - neurogranin and pTau181 - did so at the highest dose. No statistically significant changes in plasma biomarkers were observed in this short study. Long-term changes in biomarker levels and their relationship to clinical efficacy will be evaluated in the 18-month ALTITUDE-AD phase 2 study of sabirnetug beginning in the first half of 2024."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • GFAP • p-tau181 • VAMP2

Dementia Care Research and Psychosocial Factors. (PubMed, Alzheimers Dement) - "Problems reported by participants were typical to AD, although there was heterogeneity in overall AD experience. Changes in mood were frequently reported. These findings highlight the need to contextualize clinical trial results by incorporating the patient voice."

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

Acumen Pharmaceuticals Announces Journal of Prevention of Alzheimer’s Disease Publication of the Company’s Phase 1 INTERCEPT-AD Study, Including Target Engagement, Dosing Regimen and Safety Findings (GlobeNewswire) - P1 | N=65 | INTERCEPT-AD (NCT04931459) | Sponsor: Acumen Pharmaceuticals | "Acumen Pharmaceuticals, Inc...today announced that the Journal of Prevention of Alzheimer’s Disease published the results of the Phase 1 INTERCEPT-AD clinical trial...The results...demonstrated selective target engagement of AβOs in a dose-dependent and exposure-dependent manner, statistically significant amyloid plaque reduction within higher dose multiple-ascending dose cohorts, and low overall levels of amyloid-related imaging abnormalities (ARIA) with edema/effusion (ARIA-E) or hemorrhage/hemosiderin deposition (ARIA-H). One participant experienced mildly symptomatic ARIA-E, which resolved within four weeks. None of the six participants who were apolipoprotein E Ɛ4 homozygotes and received sabirnetug developed ARIA-E or ARIA-H...The first patient was dosed in ALTITUDE-AD in May 2024, and Acumen expects to complete enrollment in the first half of 2025."

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

A Study to Evaluate Efficacy and Safety of Intravenous Sabirnetug in Participants with Early Alzheimer's Disease (ALTITUDE-AD) (clinicaltrials.gov) - P2 | N=540 | Active, not recruiting | Sponsor: Acumen Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders

Acumen Pharmaceuticals to Deliver Late-Breaking Presentation at 17th Annual Clinical Trials on Alzheimer’s Disease (CTAD) Conference (GlobeNewswire) - "Acumen Pharmaceuticals, Inc...announced that it will present a late-breaking presentation featuring insights from its participant screening approach used in the ongoing Phase 2 ALTITUDE-AD clinical trial evaluating sabirnetug (ACU193), at the 17th Annual Clinical Trials on Alzheimer’s Disease (CTAD) conference taking place in Madrid, Spain, and online from Oct. 29 – Nov., 1, 2024."

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

ALTITUDE-AD: Use of a Validated p-tau217 Assay to Screen Potential Participants in an Ongoing Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Sabirnetug for Participants with Early Alzheimer's Disease (CTAD 2024) - No abstract available

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

ACU193-102: A Study Comparing the Safety, Tolerability, and Pharmacokinetics of Sabirnetug IV and Sabirnetug + rHuPH20 SC in Healthy Participants (clinicaltrials.gov) - P1 | N=28 | Completed | Sponsor: Acumen Pharmaceuticals | Recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders

Amyloid beta oligomer-associated glial pathology in Alzheimer’s Disease: Identification of an AβO subtype that binds to the earliest reactive astrocytes and is later engulfed by activated microglia (Neuroscience 2024) - "Super resolution microscopy on AD human hippocampal tissue shows ACU193+ AβOs colocalize with reactive astrocytes in a similar manner in humans as they do in mice, intimating translational significance in our findings. Taken together, our study further supports AβOs as primary pathological instigators in AD and provides evidence that early induction of reactive astrogliosis is caused by an ACU193+ AβO subtype."

Alzheimer's Disease • CNS Disorders

Amyloid beta oligomers' role in neurodevelopment may be mediated via extracellular vesicles (Neuroscience 2024) - "Primary antibodies included ACU193 (specific for AβOs), markers for vesicles (anti-LAMP-1, anti-CD81), and markers for retinal cell types (anti-ChAT, anti-Lim-1, anti-TH)...Further identification of the relationship between AβOs and cellular components during neurodevelopment would reveal specific mechanisms involved in AβO production, trafficking, and eventual down-regulation. These findings in turn would assist in identifying parallel mechanisms involved in the onset and progression of Alzheimer’s Disease and potentially provide new targets for early diagnostics and therapeutics."

Alzheimer's Disease • CNS Disorders • CD81

A Study to Evaluate Efficacy and Safety of Intravenous Sabirnetug in Participants with Early Alzheimer's Disease (ALTITUDE-AD) (clinicaltrials.gov) - P2 | N=540 | Recruiting | Sponsor: Acumen Pharmaceuticals | Phase classification: P2/3 ➔ P2 | N=2040 ➔ 540 | Trial completion date: Jan 2031 ➔ Oct 2026 | Trial primary completion date: Jan 2031 ➔ Oct 2026

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders

Acumen Pharmaceuticals Extends Collaboration with Lonza to Add Drug Product Manufacturing of Sabirnetug for Early Alzheimer’s Disease (GlobeNewswire) - "Acumen Pharmaceuticals...announced today that it has extended its collaboration with Lonza to enable the potential future commercial launch of sabirnetug (ACU193)....The extended collaboration builds upon an existing successful relationship between the two companies, in which Lonza provides DS manufacturing for the Phase 2 clinical supply of sabirnetug. Under the terms of the extended agreement, Lonza will manufacture cGMP DP of sabirnetug for the ongoing and future clinical phases and support the potential commercial launch at its industry-leading state-of-the-art DP manufacturing facility in Visp, Switzerland."

Licensing / partnership • Alzheimer's Disease