Acumen Pharmaceuticals Spotlights Sabirnetug Phase II Progress, JCR Brain-Delivery Partnership at Conference

Key Points

• Acumen’s lead antibody, sabirnetug, is in the Phase II ALTITUDE‑AD trial (542 patients enrolled) using iADRS as the primary endpoint, with top‑line 18‑month results expected in late 2026 and a company target of roughly 30–40% slowing and low ARIA rates as a success benchmark.
• Phase I data informed Phase II dosing, with 35 mg/kg and 50 mg/kg selected to bracket the pharmacodynamic curve; higher‑dose cohorts showed more ARIA‑E, suggesting a dose–safety relationship.
• Acumen’s enhanced brain delivery partnership with JCR Pharmaceuticals produced non‑human primate results showing about a 40–50‑fold increase in brain concentrations versus an unmodified antibody, and the company is aiming for an IND around mid‑2027 to enter the clinic.

Acumen Pharmaceuticals NASDAQ: ABOS executives outlined key clinical and research milestones for the company’s Alzheimer’s disease pipeline during a discussion focused on its lead antibody, sabirnetug, and an enhanced brain delivery (EBD) collaboration with Japan-based JCR Pharmaceuticals.

Company focus and 2026 as a major catalyst year

Founder and CEO Daniel O’Connell described Acumen as a biotech company pursuing better treatment options for people with Alzheimer’s disease, with sabirnetug as its lead program. He characterized sabirnetug as a humanized IgG2 monoclonal antibody designed to be “highly selective for toxic soluble Aβ oligomers,” a distinction he said could translate to clinical benefit.

O’Connell said Acumen is running a Phase II study, ALTITUDE-AD, and is also advancing a subcutaneous (subQ) format for sabirnetug. In addition, the company has an EBD program that uses transferrin receptor-mediated transport for Aβ oligomer antibodies, including sabirnetug and related constructs.

Looking ahead, management framed 2026 as a major data year. O’Connell said the Phase II ALTITUDE-AD study is expected to read out its 18-month primary outcome “late 2026,” which he described as intended to be the first “deliberate, intentional validation” of the Aβ oligomer hypothesis in a clinical setting.

What Acumen says would constitute success in Phase II

In discussing how Acumen is thinking about success for ALTITUDE-AD, O’Connell emphasized a risk-benefit framework: efficacy relative to risks associated with administration. He said the company believes sabirnetug could potentially deliver greater efficacy—citing a target of “30% or better, closer to 40%” at an 18-month endpoint—alongside a favorable safety profile, particularly regarding ARIA (amyloid-related imaging abnormalities).

He noted that an approximate 30% slowing over 18 months is a commonly cited benchmark for currently approved Alzheimer’s antibodies, and referenced ARIA rates in the “10%–12%” range as a safety benchmark for approved agents.

ALTITUDE-AD design, enrollment pace, and endpoints

O’Connell highlighted execution on ALTITUDE-AD, noting the study launched in May 2024 and completed enrollment of 542 subjects in roughly 10 months, finishing in March 2025. He described ALTITUDE-AD as a “registration quality” study with two active doses versus placebo, and said both doses could potentially be safe and efficacious.

Acumen selected the integrated Alzheimer’s Disease Rating Scale (iADRS) as the primary endpoint. O’Connell acknowledged ongoing debate in the field over preferences for iADRS versus CDR-Sum of Boxes, and said CDR-SB is a key secondary endpoint. He added that Acumen chose iADRS because it “tends to be a bit more sensitive” in the early Alzheimer’s population being enrolled.

Phase I context and why the company chose two Phase II doses

Management reviewed Phase I INTERCEPT-AD findings that informed Phase II dose selection. O’Connell said that in the multiple ascending dose portion, high-dose cohorts received three administrations (about a three-month timepoint for imaging biomarkers). At 60 mg/kg and 25 mg/kg (dosed every two weeks), he said PET plaque reduction was about 21%–22%, with the 60 mg/kg cohort showing a slightly faster reduction.

On safety, O’Connell reported a total of five cases of ARIA-E: three at 60 mg/kg (with three administrations), and one each at 10 and 25 mg/kg. He said the data appeared to show a dose relationship between ARIA-E and higher-dose cohorts. He also said fluid biomarkers supported pharmacodynamic effects after three administrations and were incorporated into modeling that informed Phase II dosing.

Chief Development Officer James Doherty added details on dose selection methodology, describing a pharmacodynamic assay that measured complexes of sabirnetug bound to soluble oligomers in cerebrospinal fluid (CSF). Doherty said plotting concentration against the oligomer-antibody bound complex showed an asymptotic relationship at higher concentrations. Based on that, Acumen selected 35 and 50 (mg/kg) for Phase II to “bracket the steep part of the curve” and the more asymptotic region at higher exposure.

Doherty said the two doses are not meant to test “two hypotheses” so much as provide separation between a lower exposure expected to be more selective for oligomers and a higher exposure that still binds oligomers but may begin picking up lower-affinity binding to larger species such as plaque.

Subcutaneous strategy and enhanced brain delivery collaboration with JCR

On subQ development, O’Connell said Acumen completed a Phase I healthy volunteer study about a year ago, but indicated the company is looking to ALTITUDE-AD outcomes to determine next steps. He said feasibility for the higher dose via subQ appears possible based on the work completed, but the strategy will depend on which dose has the best risk-benefit profile from the Phase II results. He also noted that IV administration remains part of the potential regimen in addition to subQ.

Acumen also discussed its EBD program and partnership with JCR Pharmaceuticals. O’Connell said the company began evaluating the space in 2024 amid growing interest in blood-brain barrier transport mechanisms and ultimately chose to collaborate with JCR, citing its long-standing work on transferrin receptor approaches and its IZCARGO and J-Brain Cargo platform experience. He said Acumen entered the collaboration in late 2024, publicly disclosed an option and license agreement in July, and guided toward having development candidates in late 2025 or early 2026.

Earlier in the week of the discussion, Acumen announced results from a non-human primate (NHP) study evaluating three different EBD constructs. Doherty said the constructs produced roughly “40- to 50-fold” improvements in brain concentrations relative to an unmodified antibody, and that the study had not shown significant reductions in hematological parameters associated with anemia so far. He said the company viewed JCR’s Hunter syndrome experience with IZCARGO—where it is not seeing significant anemia risk—as an important factor in selecting the partner.

When asked about timelines, management said the goal is to enter the clinic in 2027 and that the company has guided to “mid-2027” for an IND. O’Connell added that the NHP work evaluated three candidates but there are four finalists, and that under the JCR agreement Acumen can license two candidates under the same economics. He said Acumen expects to proceed with a couple of candidates toward final clinical candidate designation late this year or early next.

On commercialization strategy after the ALTITUDE-AD readout, O’Connell said Acumen would evaluate options based on the data. He said the current plan assumes a Phase III program would be needed and that the company could potentially pursue development independently or with a partner, noting Alzheimer’s studies are large and expensive and require access to resources.

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.

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