Acumen Pharmaceuticals (NASDAQ:ABOS) said it remains on track to report top-line results late in 2026 from its Phase II ALTITUDE-AD study of sabirnetug, an investigational antibody designed to selectively target synaptotoxic amyloid-beta oligomers in early Alzheimer’s disease.
Chief Executive Officer Dan O’Connell said the readout will be a key test of the company’s scientific premise that targeting amyloid-beta oligomers could provide a differentiated approach to Alzheimer’s treatment. He said the randomized study is designed to assess clinically meaningful outcomes after 18 months of treatment and is evaluating sabirnetug at 35 milligrams per kilogram and 50 milligrams per kilogram against placebo.
ALTITUDE-AD Readout Approaches
O’Connell said prior Phase I findings showed amyloid-beta oligomer target engagement and biomarker changes as early as three months of treatment. He said Acumen believes the Phase II study, which he characterized as well powered, could expand on those earlier findings.
The company also presented patient-experience data at the Alzheimer’s Association International Conference in London last month. O’Connell said the data, collected from ALTITUDE-AD participants and their study partners before treatment, illustrated the differing ways people with early Alzheimer’s experience and respond to cognitive and functional changes.
When asked about another company’s blinded interim assessment involving an oligomer-specific approach, O’Connell said Acumen did not believe much could be concluded from the early-stage disclosure. He pointed instead to Acumen’s own Phase I results and said the company saw effects on fluid and imaging biomarkers after three doses.
Acumen is preparing activities intended to reduce the time between a potentially favorable Phase II outcome and a Phase III program. O’Connell said work is ongoing across manufacturing, clinical-site planning and other areas, though he noted that regulatory discussions regarding a Phase III design would follow the data. The company hopes a successful ALTITUDE-AD outcome could support moving sabirnetug into a single pivotal Phase III study.
Safety Profile and Biomarker Plans
Chief Medical Officer Eric Siemers said sabirnetug may have safety and tolerability distinctions from other anti-amyloid antibodies because it targets oligomers rather than plaque and is an IgG2 antibody. He said IgG2 antibodies have less effector function than IgG1 antibodies, meaning they have less immune-system activation. According to Siemers, that could be relevant to risks such as ARIA, though he said the ALTITUDE-AD results will determine the treatment’s profile.
Siemers said Acumen uses p-tau217 as part of its screening process for ALTITUDE-AD and will also evaluate it as an outcome measure after the study is unblinded. The company did not include MTBR-tau243 in the original study design because the biomarker was less established at that time, he said. However, Acumen has stored plasma samples from a large patient population and may evaluate MTBR and other emerging blood-based biomarkers after the study.
President and Chief Development Officer James Doherty said the company’s July collaboration with Unlearn.AI will use “digital twins” as an exploratory endpoint. The models use data from previously studied patients to estimate an individual’s likely disease progression based on baseline characteristics. Doherty said the technology could potentially assist with patient selection or serve as a prognostic covariate, but Acumen is initially evaluating how useful the approach may be.
Brain-Delivery Program Advances
Acumen also highlighted two enhanced brain delivery, or EBD, candidates: ACU301 and ACU401. The company exercised an option with JCR Pharmaceuticals to advance the programs, which combine blood-brain barrier-penetrating technology with antibodies targeting amyloid-beta oligomers.
ACU301 is a bispecific antibody incorporating sabirnetug, while ACU401 includes ACU234, a next-generation amyloid-beta oligomer-selective antibody. O’Connell said Acumen intends to select one candidate for clinical development after continuing work on both molecules. The company anticipates filing an investigational new drug application for its lead EBD candidate in mid-2027.
At AAIC, Acumen presented non-human primate findings showing that all three EBD bispecific antibodies tested achieved greater brain exposure after intravenous administration than unmodified ACU234. O’Connell said ACU401 achieved up to 40-fold greater frontal-cortex exposure in cynomolgus monkeys and increased exposure in deep brain regions.
Doherty said the candidate-selection process evaluated factors including transferrin receptor affinity, antibody valency and potential anemia risk. The company is still determining its initial clinical study design and has not made a final decision on whether to begin in healthy volunteers or move directly to patients.
Second-Quarter Financial Results
Chief Financial Officer and Chief Business Officer Matt Zuga said Acumen ended the second quarter with $110.2 million in cash and marketable securities, which the company expects will fund current clinical and operational activities into early 2027.
- Research and development expense was $27.8 million, down from the prior-year period primarily due to lower manufacturing, materials and contract research organization costs.
- General and administrative expense was $4.7 million, roughly unchanged from a year earlier.
- Loss from operations totaled $32.6 million.
- Net loss was $32.7 million for the second quarter.
Acumen plans to hold a virtual investor relations day on Sept. 16, which Head of Investor Relations Alex Braun said will provide an overview of the company’s investment thesis, sabirnetug and the EBD program ahead of the Phase II data release.
About Acumen Pharmaceuticals (NASDAQ:ABOS)
Acumen Pharmaceuticals, Inc is a clinical-stage biopharmaceutical company focused on the discovery and development of oral small molecule therapies for neurodegenerative diseases. Leveraging a proprietary drug discovery platform that integrates chemoproteomics, high-throughput screening and computational chemistry, the company seeks to identify and optimize compounds that selectively modulate pathological protein aggregation. Its approach is designed to address the underlying biology of conditions such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and related proteinopathies.
The company’s pipeline comprises multiple lead candidates at various stages of preclinical and early clinical development.
