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

Anticipated Milestones (The Manila Times) - "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 is targeting the submission of an IND filing with respect to a lead clinical candidate in its EBD program in mid-2027."

IND • P2 data • Pipeline update • Alzheimer's Disease

Elucidating the phase 1 trial experience among study participants following completion of the INTERCEPT-AD study of sabirnetug (ACU193) for early Alzheimer's disease: a qualitative interview study. (PubMed, Trials) - "Study findings suggest opportunities to enhance the AD trial experience by addressing trial-related burdens and logistical aspects of participation. Exploratory gender analyses yielded additional insight into the patient trial experience but should be further examined along with race/ethnicity and study partner characteristics to enhance clinical study design and execution."

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

SABIRNETUG BIOMARKER TREATMENT RESPONSES: EXPLORATORY EVALUATION OF THE CNS DISEASE PANEL NULISA-SEQ-TM (ADPD 2026) - "AT(N) biomarker correlations were identified between different proteoforms of Aß and pTau. Aß38, pTau231 and NFL-H/L, amongst other candidate proteins, were identified as novel pharmacodynamic biomarkers. The results further support the downstream pathophysiological changes affected by sabirnetug treatment in AD."

Biomarker • Alzheimer's Disease • CNS Disorders • GFAP • NEFH • p-tau181

ENHANCED BRAIN DELIVERY OF SABIRNETUG AFTER FUSION WITH AN ANTI-TRANSFERRIN RECEPTOR ANTIBODY FRAGMENT IN A MOUSE MODEL OF ALZHEIMER'S DISEASE (ADPD 2026) - "Use of the J-Brain Cargo® technology that targets the TfR is a promising approach to increase brain penetration of candidate AD immunotherapeutic agents such as sabirnetug. This is expected to enable lower dosing to achieve efficacy and to support a potentially improved safety profile. Efforts are ongoing to further examine fusion proteins of sabirnetug with antibody fragments targeting human TfR."

Preclinical • Alzheimer's Disease • CNS Disorders • Solid Tumor

Sabirnetug Biomarker Treatment Responses: Exploratory Evaluation of the CNS Disease Panel NULISAseq (GlobeNewswire) - "The Phase 1 INTERCEPT‑AD study demonstrated clear, treatment‑related biomarker changes following a brief sabirnetug administration. Acumen used the protein-multiplex NULISAseq CNS Disease Panel to measure 127 proteins reflecting amyloid and tau pathology, synaptic function, neuroinflammation and neurodegeneration. Sabirnetug‑associated effects were observed in key Alzheimer’s disease biomarkers, including the pTau217/Aβ42 ratio, Aβ1‑38, and GFAP....A dedicated bioanalytical database has now been established to enable expanded exploratory analyses, including integration with the ongoing Phase 2 ALTITUDE‑AD study."

Biomarker • Diagnostic • P1 data • Trial status • Alzheimer's Disease

Enhanced Brain Delivery of Sabirnetug After Fusion with an Anti-Transferrin Receptor Antibody Fragment in a Mouse Model of Alzheimer’s Disease (GlobeNewswire) - "Using J-Brain Cargo, JCR’s clinically validated platform targeting the transferrin receptor (TfR) to facilitate brain uptake, the teams prepared three Bispecific Antibodies of sabirnetug with antibody fragments targeting murine TfR (mTfR), each with varying mTfR affinities. The AβO affinity and selectivity of each fusion protein were measured via surface plasmon resonance (SPR), while plasma and total brain pharmacokinetics were measured in wild-type mice following a 2 mg/kg IV injection; brain exposure and target engagement were assessed in ARTE10 AD mice 24 hours after the 2 mg/kg IV injection with immunohistochemistry. Findings demonstrate that Acumen’s EBD technology utilizing TfR increases sabirnetug brain exposure while preserving target engagement as demonstrated by AβO selectivity."

Preclinical • Alzheimer's Disease

Expected Centiloid Values for Patients with Positive Visual Reads of Amyloid PET Scans (AAN 2026) - "In the phase 3 CLARITY study of lecanemab (n=1734), CL values at baseline ranged from -17 to 213.2 for visually positive PET scans. ALTITUDE-AD is an ongoing phase 2 study of sabirnetug that has completed enrollment of 542 participants with MCI or mild dementia due to AD... The actual range of CL values for individuals with MCI or mild dementia with visually positive amyloid scans is likely wider than 0 to 100. The preliminary baseline CL values from the ALTITUDE-AD study are consistent with the published literature. Overreliance on CL cut-offs may bias against the detection of clinically relevant early amyloid deposition."

Amyloid PET • Clinical • Alzheimer's Disease • CNS Disorders • Dementia

Acumen Pharmaceuticals to Showcase Advances in Alzheimer's Treatment at International Conference on Alzheimer’s and Parkinson’s Diseases 2026 (The Manila Times) - "The presentations will highlight new data regarding enhanced brain delivery (EBD) of sabirnetug, sabirnetug biomarker treatment responses, and the development of new AβO-targeting antibodies. The conference will be held in-person and online March 17-21, 2026."

P1 data • Preclinical • Alzheimer's Disease

Drug Development. (PubMed, Alzheimers Dement) - P2 | "Compared to the recombinant Aβ monoclonal antibody therapeutics tested, sabirnetug showed the highest selectivity for AβOs over monomeric Aβ. Sabirnetug's observed high level of selectivity makes it well positioned to target AβOs in MCI/AD tissues and biofluids."

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

Drug Development. (PubMed, Alzheimers Dement) - P2 | "Participants tested by amyloid PET or CSF Aβ42/40 were enriched for meeting amyloid-based inclusion criteria and the screening cost was reduced by approximately US $10 million (∼40%). Additionally, the pTau217 screening strategy helped reduce the unnecessary burden of PET scans and LP procedures for potential participants."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • Aβ42 • CSF Aβ42

Developing Topics. (PubMed, Alzheimers Dement) - "ACU193 and r-lecanemab differ in their concentration-dependent binding, labeling of non-vascular and vascular Aβ, fibrillar selectivity and regional patterns. Fixation time influenced antibody binding, particularly non-vascular staining. Double-label analyses with markers of Aβ, vasculature, neurons, and dystrophic neurites are underway to provide further insight into the localization of antibody binding. Funding_1R01NS136122-01_CAL."

Journal • Alzheimer's Disease • CNS Disorders

Developing Topics. (PubMed, Alzheimers Dement) - "Immunoaffinity chromatography confirms that, as with synthetic AβOs, the AβOs in AD brain targeted by ACU193 are globular. r-mAb148, the murine precursor of Leqembi, isolates globular and protofibrillar AβOs, extending reports that affinity purification yields fibrils from AD brain. ACU193 also recognizes protofibrils found in 5xFAD but not human brain. Experiments are in progress to evaluate the impact of chromatography method and extract preparation on particle morphology, to evaluate pathological impact in cell assays, to determine oligomer substructures by native mass spectrometry, and to determine high-resolution structural details by cryoEM."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation

Identification of a glia-associated amyloid β oligomer subtype and the rescue from reactive astrogliosis by inhibitor NU-9. (PubMed, Alzheimers Dement) - "ACU193+ AβOs accumulated as puncta in neurons at an early stage of degeneration, while NU4+ AβOs appeared as dense deposits only in late-stage degenerating neurons. The onset and progression of ACU193+ AβOs paralleled activated microglia and reactive astrocytes. ACU193+ AβOs significantly increased on reactive astrocyte surfaces, as NU4+ AβOs accumulated in halos around Thio-S+ plaque cores. In older mice, the ACU193 signal decreased on astrocytes and was found inside activated microglia. Sixty-day oral NU-9 treatment significantly reduced astrocyte ACU193+ AβOs and markedly decreased reactive astrogliosis."

Journal • Alzheimer's Disease • CNS Disorders • GFAP

Fusing Transferrin Receptor Binders to the A?O-targeting Antibody Sabirnetug Achieves Increased Brain Penetration in Mice While Preserving Target Binding (CTAD 2025) - No abstract available

Preclinical

ALTITUDE-AD: Recruitment strategies for a global phase 2 trial of sabirnetug in early Alzheimer's disease (CTAD 2025) - No abstract available

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

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