Acumen Pharmaceuticals Highlights Enhanced Brain Delivery™ Technology for Oligomer-Selective Antibodies and Recruitment Strategies for Phase 2 ALTITUDE-AD Clinical Trial at 18th Annual Clinical Trials on Alzheimer’s Disease (CTAD) Conference

Rhea-AI Summary

Acumen Pharmaceuticals (NASDAQ: ABOS) presented new preclinical and clinical-trial recruitment data at the 18th Annual CTAD conference on December 1-4, 2025. A collaborative study with JCR Pharmaceuticals showed that fusing transferrin receptor (TfR) binders to AβO-targeting antibodies (including sabirnetug/ACU193) produced 15–68 fold increases in brain penetration in mice while preserving target binding. Acumen and JCR are developing TfR-targeting antibodies for clinical testing. Recruitment analysis from the Phase 2 ALTITUDE-AD trial tracked 2,362 screened across 76 sites with 542 enrolled, finding site databases and physician referrals were the most reliable recruitment methods.

Positive

• Brain penetration increased 15–68× in mice
• 542 enrolled from 2,362 screened in ALTITUDE-AD
• Acumen and JCR developing TfR-targeting antibodies for clinical testing

Negative

• Preclinical brain-penetration data observed only in mice
• Enrollment rate ~23% (542/2,362), indicating high screening needs

Key Figures

Brain penetration gain 15–68 fold increase Fusion proteins vs. standard antibodies in mice following IV administration

Baseline brain penetration <1% of delivered dose Typical brain exposure after IV IgG antibody delivery

Participants screened 2,362 participants Phase 2 ALTITUDE-AD recruitment analysis across global sites

Participants enrolled 542 participants ALTITUDE-AD trial enrollees from screened population

Trial sites 76 sites Global Phase 2 ALTITUDE-AD clinical trial footprint

Recruitment methods 6 methods ALTITUDE-AD recruitment channels; site databases and referrals most effective

Market Reality Check

$2.17 Last Close

Volume Volume 155,307 is close to the 20-day average of 158,072, suggesting typical trading interest before this update. normal

Technical Shares at $1.96 are trading above the $1.41 200-day moving average but sit 20.33% below the 52-week high and above the 52-week low by 129.21%.

Peers on Argus

ABOS was down 2.56% while key biotech peers showed mixed moves: declines in CRVO (-4.43%), IMUX (-6.29%) and XBIT (-1.92%), but gains in ATRA (8%) and OVID (1.85%). This points to stock-specific trading rather than a uniform sector trend.

Common Catalyst Same-day peer news includes neurology-focused updates (e.g., CRVO dementia biomarker data), suggesting broader CNS conference/news flow but company-specific price reactions.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 02	CTAD delivery data	Positive	-7.9%	Presented brain-delivery and recruitment data for sabirnetug and ALTITUDE-AD at CTAD.
Nov 17	OLE dosing start	Positive	-8.7%	First participant dosed in Phase 2 open-label extension of sabirnetug trial.
Nov 12	Q3 2025 earnings	Neutral	-1.0%	Reported Q3 2025 results, cash of <b>$136.1M</b>, runway into early 2027 and pipeline timelines.
Nov 10	Chairman appointment	Positive	+0.5%	Appointed experienced biopharma executive George Golumbeski as Board Chairman.
Nov 05	Earnings date set	Neutral	+4.6%	Announced timing and webcast details for upcoming Q3 2025 earnings call.

Pattern Detected

Recent history shows multiple clinically focused and operationally positive updates accompanied by flat-to-negative next-day price moves, indicating a tendency for the stock to trade weakly around constructive news.

Recent Company History

Over the last several months, ABOS has repeatedly highlighted progress in its sabirnetug program and related platforms. In March 2025 it completed enrollment of the 542-patient Phase 2 ALTITUDE-AD trial. Subsequent clinical and screening-data presentations in March–July 2025 emphasized assay efficiency and oligomer selectivity. More recently, in November 2025, the company initiated an open-label extension and reported Q3 2025 financials with cash supporting operations into early 2027. Today’s CTAD data on Enhanced Brain Delivery and recruitment strategies extend this same development arc.

Market Pulse Summary

The stock moved -7.9% in the session following this news. A negative reaction despite supportive preclinical and recruitment data fits prior patterns where clinical updates often saw next-day declines, such as -8.67% after the open-label extension dosing news. The CTAD results still relied on animal models for brain delivery, and clinical validation remains pending. With ALTITUDE-AD topline results not expected until a later date, extended timelines and ongoing trial costs could have weighed on sentiment even as operational execution appeared to progress.

Key Terms

amyloid beta oligomers medical

"developing a novel therapeutic that targets soluble amyloid beta oligomers (AβOs)"

Small, soluble clumps of a brain protein called amyloid beta that can interfere with nerve cell function and are suspected to drive memory loss in neurodegenerative disease. Investors watch them because drugs that reduce or neutralize these oligomers are a major focus of research, and convincing evidence that a treatment affects them can sway clinical trial success, regulatory decisions and a company’s valuation — like finding the right lock-and-key to stop engine damage.

transferrin receptor medical

"through the blood-brain barrier using the transferrin receptor (TfR) pathway"

A transferrin receptor is a protein on the surface of many cells that acts like a doorway for iron-carrying transferrin to enter the cell; iron is essential for cell growth and metabolism. Investors watch it because changes in its level or function can indicate disease activity, serve as a biomarker, or be used as a delivery target for drugs and diagnostic agents — think of it as a lock drug makers can exploit to get therapies into specific cells.

blood-brain barrier medical

"delivery of AβO-targeting monoclonal antibodies to the central nervous system, including sabirnetug (ACU193), through the blood-brain barrier"

A protective barrier of tightly packed cells and supporting tissue that controls what substances in the blood can enter the brain, acting like a security checkpoint that keeps out most pathogens and many drugs while allowing essential nutrients through. For investors, the barrier matters because whether a therapy can cross or safely bypass it often determines clinical success, regulatory approval and commercial potential for treatments of brain disorders.

central nervous system medical

"delivery of AβO-targeting monoclonal antibodies to the central nervous system, including sabirnetug"

The central nervous system (CNS) is the body's main control center, made up of the brain and spinal cord, that processes information and directs movement, sensation and basic functions like breathing. For investors, CNS-related products and research matter because they face long development times, strict safety testing and regulatory hurdles; success or failure can dramatically affect a company’s costs, timelines and potential market value.

monoclonal antibodies medical

"murine TfR-binding antibody fragments from the J-Brain Cargo® platform were fused with ACU193 or ACU234, monoclonal IgG2 antibodies"

Monoclonal antibodies are lab-made proteins designed to bind a single, specific target on cells or viruses, like identical keys cut to fit one lock. They are used as medicines, tests, or targeted delivery tools and can precisely block or mark disease processes. Investors care because they can become high-value drugs with large sales, long patent protection, and binary risks tied to clinical trial results, regulatory approval, manufacturing scale and pricing.

intravenous medical

"Intravenous delivery of IgG antibodies results in poor brain penetration"

Intravenous means delivering a drug, fluid or substance directly into a vein so it goes straight into the bloodstream. For investors, that matters because intravenous products often act faster, require different manufacturing, regulatory steps and healthcare settings (like hospitals or clinics), and can affect pricing, adoption and revenue profiles in ways that differ from pills or topical treatments — like turning a slow-release delivery into a direct tap to the system.

transcytosis medical

"TfR -mediated transcytosis is a promising approach that offers the potential to enhance the brain levels"

Transcytosis is a cellular process where a cell moves a substance from one side to the other by engulfing it, carrying it through its interior, and releasing it on the opposite side — like a courier taking a package through a building. For investors, transcytosis matters because it determines whether large drugs, antibodies or delivery particles can reach protected tissues (for example the brain), affecting a therapy's effectiveness, development risk, regulatory hurdles and market value.

cerebral arteries medical

"while simultaneously limiting exposure to vascular amyloid found primarily in cerebral arteries"

Cerebral arteries are the blood vessels that deliver oxygen-rich blood to the brain, acting like main streets that supply every neighborhood of the organ. They matter to investors because disease or injury to these arteries — such as blockages or ruptures — drives demand for drugs, surgical devices, imaging tools and long-term care, which can affect the revenue and valuation of companies in healthcare and medical technology.

AI-generated analysis. Not financial advice.

NEWTON, Mass., Dec. 02, 2025 (GLOBE NEWSWIRE) -- Acumen Pharmaceuticals, Inc. (NASDAQ: ABOS), a clinical-stage biopharmaceutical company developing a novel therapeutic that targets soluble amyloid beta oligomers (AβOs) for the treatment of Alzheimer’s disease (AD), today announced new research at the 18th Annual Clinical Trials on Alzheimer’s Disease (CTAD) conference, taking place December 1-4, 2025, in San Diego and online. Results from a collaborative study with JCR Pharmaceuticals demonstrated improved delivery of AβO-targeting monoclonal antibodies to the central nervous system, including sabirnetug (ACU193), through the blood-brain barrier using the transferrin receptor (TfR) pathway, which is being developed to potentially increase and broaden brain distribution and maximize the efficacy-to-safety ratio. Building on these results, Acumen and JCR Pharmaceuticals are now developing TfR-targeting antibodies for clinical testing. Additionally, results on clinical trial recruitment from the Phase 2 ALTITUDE-AD clinical trial showed that site databases and physician referrals were the most reliable recruitment methods overall.

“The data we're presenting at CTAD highlights two critical aspects of successful Alzheimer's drug development,” said Jim Doherty, PhD, President and Chief Development Officer of Acumen Pharmaceuticals. “This research is advancing the understanding of two major challenges in the treatment of Alzheimer’s disease – targeted drug delivery into the CNS and clinical trial execution. Our research with JCR Pharmaceuticals on transferrin receptor approaches and our insights into strategic trial recruitment represent meaningful contributions that we believe will benefit the broader effort to develop effective therapeutics for Alzheimer’s disease.”

Fusing Transferrin Receptor Binders to the AβO-targeting Antibody Sabirnetug Achieves Increased Brain Penetration in Mice While Preserving Target Binding

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.

ALTITUDE-AD: Recruitment strategies for a global phase 2 trial of sabirnetug in early Alzheimer’s disease

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.

The data posters presented will be available after each poster session concludes on the Company's website at: https://acumenpharm.com/publications/.

About Sabirnetug (ACU193)

Sabirnetug (ACU193) is a humanized monoclonal antibody (mAb) discovered and developed based on its selectivity for soluble amyloid beta oligomers (AβOs), which are a highly toxic and pathogenic form of Aβ, relative to Aβ monomers and amyloid plaques. Soluble AβOs have been observed to be potent neurotoxins that bind to neurons, inhibit synaptic function and induce neurodegeneration. By selectively targeting toxic soluble AβOs, sabirnetug aims to address the hypothesis that soluble AβOs are an early and persistent underlying cause of the neurodegenerative process in Alzheimer’s disease (AD). Sabirnetug has been granted Fast Track designation for the treatment of early AD by the U.S. Food and Drug Administration and is currently being evaluated in a Phase 2 study in patients with early AD.

About ALTITUDE-AD (Phase 2)

Initiated in 2024, ALTITUDE-AD is a Phase 2, multi-center, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of sabirnetug (ACU193) infusions administered once every four weeks in slowing cognitive and functional decline as compared to placebo in participants with early Alzheimer's disease. The study has enrolled 542 individuals with early Alzheimer’s disease (mild cognitive impairment or mild dementia due to AD) at multiple investigative sites located in the United States, Canada, the European Union and the United Kingdom. More information can be found on www.clinicaltrials.gov, NCT identifier NCT06335173.

About Acumen Pharmaceuticals, Inc.

Acumen Pharmaceuticals is a clinical-stage biopharmaceutical company developing a novel therapeutic that targets toxic soluble amyloid beta oligomers (AβOs) for the treatment of Alzheimer’s disease (AD). Acumen’s scientific founders pioneered research on AβOs, which a growing body of evidence indicates are early and persistent triggers of Alzheimer’s disease pathology. Acumen is currently focused on advancing its investigational product candidate, sabirnetug (ACU193), a humanized monoclonal antibody that selectively targets synaptotoxic AβOs, in its ongoing Phase 2 clinical trial ALTITUDE-AD (NCT06335173) in early symptomatic Alzheimer’s disease patients, following positive results in its Phase 1 trial INTERCEPT-AD. The company is headquartered in Newton, Mass. For more information, visit www.acumenpharm.com.

About the J-Brain Cargo^® Platform Technology

JCR Pharmaceuticals has developed a proprietary blood-brain barrier (BBB)-penetrating technology, J-Brain Cargo^®, to bring biotherapeutics into the central nervous system (CNS). The first drug developed based on this technology is IZCARGO^® (INN: pabinafusp alfa) and is approved in Japan for the treatment of a lysosomal storage disorder.

About JCR Pharmaceuticals Co., Ltd.

JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceutical company that develops treatments that go beyond rare diseases to solve the world’s most complex healthcare challenges. We continue to build upon our 50-year legacy in Japan while expanding our global footprint into the U.S., Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, MPS II (Hunter syndrome), Fabry disease, acute graft-versus host disease, and renal anemia. Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, MPS IIIA and B (Sanfilippo syndrome type A and B), and more. Our core values – Putting people first, Forging our own path, Always advancing, and Committed to excellence – mean that the work we do benefits all our stakeholders, including partners, patients and employees. We strive to expand the possibilities for patients while accelerating medical advancement at a global level. For more information, please visit JCR’s global website: https://jcrpharm.com/.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Any statement describing Acumen’s goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Words such as “potential,” “will” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements include statements concerning the therapeutic potential and potential clinical efficacy of Acumen’s product candidate, sabirnetug (ACU193) and Enhanced Brain Delivery technology. These statements are based upon the current beliefs and expectations of Acumen’s management, and are subject to certain factors, risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing safe and effective human therapeutics. Such risks may be amplified by the impacts of geopolitical events and macroeconomic conditions, such as rising inflation and interest rates, supply disruptions and uncertainty of credit and financial markets. These and other risks concerning Acumen’s programs are described in additional detail in Acumen’s filings with the Securities and Exchange Commission (“SEC”), including in Acumen’s most recent Annual Report on Form 10-K, and in subsequent filings with the SEC. Copies of these and other documents are available from Acumen. Additional information will be made available in other filings that Acumen makes from time to time with the SEC. These forward-looking statements speak only as of the date hereof, and Acumen expressly disclaims any obligation to update or revise any forward-looking statement, except as otherwise required by law, whether, as a result of new information, future events or otherwise.

Investors:
Alex Braun
abraun@acumenpharm.com

Media:
Elizabeth Coleman
ICR Healthcare
AcumenPR@icrhealthcare.com

FAQ

What did Acumen (ABOS) present at CTAD December 1–4, 2025?

Acumen presented TfR-fusion preclinical data showing 15–68× brain penetration increases in mice and ALTITUDE-AD recruitment results.

How much did brain delivery improve for ACU193 in the mouse study?

Fusion proteins showed a 15 to 68 fold increase in brain penetration in mice.

What were ALTITUDE-AD screening and enrollment figures for ABOS Phase 2?

The trial screened 2,362 participants across 76 sites and enrolled 542 participants.

Which recruitment methods were most effective in the ALTITUDE-AD trial?

Site databases and physician referrals were the most reliable recruitment methods overall.

Is the TfR fusion data clinical proof of efficacy for ABOS therapies?

No; the reported TfR fusion results are preclinical (mice) and do not constitute clinical proof.