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

ALTITUDE-AD: Recruitment strategies for a global phase 2 trial of sabirnetug in early Alzheimer’s disease (GlobeNewswire) - "Acumen shares study insights from analyzed recruitment data from its Phase 2 ALTITUDE-AD trial to help optimize early AD trial enrollment. The study tracked 2,362 participants screened across 76 sites, with 542 ultimately enrolled. Of the six recruitment methods utilized, site databases and physician referrals were most effective for recruiting due to established relationships and pre-screened eligibility. These findings provide the field with actionable insights for improving trial recruitment efficiency and reducing screen failure rates in future early AD studies."

P2 data • Alzheimer's Disease

Fusing Transferrin Receptor Binders to the AβO-targeting Antibody Sabirnetug Achieves Increased Brain Penetration in Mice While Preserving Target Binding (GlobeNewswire) - "Intravenous delivery of IgG antibodies results in poor brain penetration, with typically less than 1% of the delivered dose reaching the brain. To overcome this limitation, murine TfR-binding antibody fragments from the J-Brain Cargo platform were fused with ACU193 or ACU234, monoclonal IgG2 antibodies targeting soluble AβO species. The resulting fusion proteins demonstrated 15 to 68 fold increases in brain penetration following intravenous administration in mice. The potency and selectivity for soluble AβO species of these fusion proteins was maintained in mouse models of Alzheimer’s disease. TfR -mediated transcytosis is a promising approach that offers the potential to enhance the brain levels of soluble ABO-targeting antibodies like ACU193 and ACU234, while simultaneously limiting exposure to vascular amyloid found primarily in cerebral arteries."

Preclinical • Alzheimer's Disease

Relationship between efficacy and preferential targeting of soluble Aβ aggregates. (PubMed, Alzheimers Dement (N Y)) - "These results suggest that selectivity for soluble toxic oligomers correlates with clinical efficacy, potentially attenuating monomer competition and amyloid-related imaging abnormalities (ARIA)."

Journal • Alzheimer's Disease • CNS Disorders • Hematological Disorders

Acumen Pharmaceuticals Announces First Participant Dosed in Phase 2 Open-Label Extension Study of Sabirnetug in People with Early Alzheimer’s Disease (GlobeNewswire) - "Acumen expects to report topline results from ALTITUDE-AD in late 2026."

P2 data • Trial status • Alzheimer's Disease

In November 2025, the Company expects the first patient to be dosed in the open-label extension (OLE) portion of its Phase 2 ALTITUDE-AD clinical trial evaluating sabirnetug (ACU193) in patients with early Alzheimer’s disease. (GlobeNewswire) - "The OLE provides all participants who completed the 18-month placebo-controlled double-blind portion of ALTITUDE-AD with the opportunity to receive sabirnetug at 35 mg/kg administered intravenously once every four weeks for up to 52 weeks."

Trial status • Alzheimer's Disease

Anticipated Milestones (GlobeNewswire) - "The Company expects non-clinical data to support the development of an EBD therapy in early 2026, at which point Acumen has an exclusive right to exercise its option to develop up to two development candidates as part of its partnership with JCR Pharmaceuticals; The Company expects topline results from ALTITUDE-AD, a Phase 2 study to investigate sabirnetug for the treatment of early Alzheimer’s disease, in late 2026."

P2 data • Preclinical • Alzheimer's Disease

Recruitment and eligibility in a Phase 1 early Alzheimer's disease trial of Sabirnetug. (PubMed, Alzheimers Dement (N Y)) - "Diverse recruitment tactics, customized to capabilities of study sites and patient populations, may be more successful in recruiting diverse populations than a one-size-fits-all approach. Although a diverse pool of potential participants was screened, a less diverse group was enrolled, largely due to race- and ethnicity-related disparities in screening eligibility rates. Further investigation is needed to assess equitable screening methods for AD clinical trials."

Journal • P1 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

ALTITUDE-AD: Cost savings using a pTau217 screening assay in an ongoing Phase 2 study of sabirnetug in early Alzheimer's disease (GlobeNewswire) - "Acumen reported operational innovations in its ALTITUDE-AD Phase 2 clinical trial where researchers implemented an innovative two-step screening process using plasma pTau217 biomarker assay testing that yielded significant clinical trial screening and cost efficiencies. The approach reduced total screening costs by approximately 40% across U.S. and Canadian sites....Furthermore, the screening process was efficient, with 48% of participants meeting the pTau217 threshold required for confirmatory testing. Among those who passed this initial screening, 81% of participants successfully met amyloid positivity eligibility requirements. The strategy performed as intended, helping to achieve strong enrollment rates and reducing unnecessary amyloid PET scans and lumbar puncture procedures for potential participants."

HEOR • Alzheimer's Disease

Anticipated Milestones (GlobeNewswire) - "The Company expects topline results from ALTITUDE-AD, a Phase 2 study to investigate sabirnetug for the treatment of early Alzheimer’s disease, in late 2026; The Company expects non-clinical data to support the development of an EBD therapy in early 2026, at which point Acumen has an exclusive right to exercise its option to develop up to two development candidates as part of its partnership with JCR."

P2 data • Preclinical • Alzheimer's Disease

Acumen Pharmaceuticals to Present Studies on Cost Savings Associated with Use of pTau217 Screening Assay in Phase 2 ALTITUDE-AD Study and Sabirnetug Oligomer-Selectivity at the Alzheimer’s Association International Conference (AAIC) 2025 (GlobeNewswire) - "Acumen Pharmaceuticals...will present new findings at the upcoming Alzheimer's Association International Conference (AAIC) 2025 in Toronto. The presentations include a cost savings analysis of the use of pTau217 as a screening tool in Acumen’s Phase 2 ALTITUDE-AD trial of sabirnetug as well as a nonclinical study evaluating the relative selectivity of sabirnetug to targeting AβOs versus Aβ monomers. The conference will be held July 27-31, 2025, both in-person and online."

HEOR • Preclinical • Alzheimer's Disease

Sabirnetug shows superior selectivity for Aβ oligomers over monomer, a differentiated mechanism of action. (GlobeNewswire) - "Acumen demonstrated sabirnetug's selectivity for binding to toxic AβOs through comprehensive surface plasmon resonance testing. The study revealed sabirnetug achieved the highest binding affinities to AβO preparations among the monoclonal antibodies tested. Sabirnetug also showed minimal interaction with monomeric Aβ, which is significant given that monomeric forms are approximately 7,000-fold more abundant than oligomers in the cerebrospinal fluid of patients with MCI and mild dementia due to AD. Overall, sabirnetug demonstrated 8,750-fold selectivity for Aβ1-42 stabilized oligomers over Aβ1-40 monomers. The results support sabirnetug’s mechanism of action and selectivity for AβOs."

Preclinical • Alzheimer's Disease

Acumen Pharmaceuticals Reports First Quarter 2025 Financial Results and Business Highlights (GlobeNewswire) - "Anticipated Milestones: The Company expects topline results from ALTITUDE-AD, a Phase 2 study to investigate sabirnetug for the treatment of early Alzheimer’s disease, in late 2026."

P2 data • Alzheimer's Disease

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