VAMP2

NEWTON, Mass., July 28, 2024 (GLOBE NEWSWIRE) -- Acumen Pharmaceuticals, Inc. (NASDAQ: ABOS), 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), today announced new findings from its Phase 1 INTERCEPT-AD study of sabirnetug (ACU193). The research highlights the experiences of patients in the clinical trial to inform development of future trials, biomarker data to support sabirnetug’s mechanism of action, and an ultra-sensitive method of measuring small amounts of sabirnetug in cerebrospinal fluid (CSF). The posters will be presented at the Alzheimer’s Association International Conference (AAIC®) 2024 taking place in Philadelphia and online from July 28-Aug. 1, 2024. Sabirnetug is the first humanized monoclonal antibody to demonstrate in patients with early symptomatic AD selective target engagement of AβOs, a soluble and highly toxic form of Aβ that accumulates early in AD and is a persistent trigger of synaptic dysfunction and neurodegeneration. Acumen is developing sabirnetug as a potential best-in-class antibody treatment for early symptomatic AD. “These findings from our Phase 1 study of sabirnetug highlight not only the strength of the study design with participants having early symptomatic AD but also continue to support the potential for sabirnetug as a best-in-class treatment," said Eric Siemers, M.D., Chief Medical Officer of Acumen. “Our research reflects our focus on incorporating the patient voice into drug development, provides further support for the mechanism of action of sabirnetug, and includes developing powerful tools for drug development with an assay that can measure even small amounts of sabirnetug bound to toxic soluble amyloid beta oligomers in patients in our clinical trials. These insights can help us as we advance clinical studies of sabirnetug, including our ongoing Phase 2 study. As recently approved therapies for Alzheimer’s gain traction, we have an opportunity to advance a next-generation treatment that has the potential to optimize the benefit-risk ratio compared to first-generation disease-modifying treatments for AD.” Understanding the Patient Experience in INTERCEPT-AD Acumen is putting patients first by incorporating the patient voice in drug development. Acumen conducted exit interviews in a subset of patients from the INTERCEPT-AD trial to understand their experience with MCI and mild AD and expectations for treatment. Acumen also obtained feedback on topics such as the decision-making process preceding trial enrollment and the overall trial experience, and examined the results by participant gender to guide planning for future clinical trials. Participants reported a broad array of symptoms consistent with AD, most frequently difficulty with memory or cognitive functioning. Nearly every participant desired treatment that would keep the disease from getting worse or slow progression. Additionally, participants wanted a new treatment that would help them maintain the ability to recognize loved ones and maintain or improve communication abilities. Sabirnetug Lowers CSF Levels of Synaptic Biomarkers The study revealed that three administrations of sabirnetug significantly lowered CSF levels of both pre- and post-synaptic proteins, consistent with its proposed mechanism of action to inhibit synaptic binding of AβOs. VAMP2, a biomarker associated with synaptic injury, was significantly lowered in all multiple ascending dose cohorts and appeared to be the biomarker most sensitive to sabirnetug in this study. Acumen is planning to evaluate longer-term changes in biomarkers and their relationship to clinical outcomes in the ongoing 18-month Phase 2 clinical trial ALTITUDE-AD to further support sabirnetug’s mechanism of action. Developing a Highly Sensitive Assay to Detect Sabirnetug in CSF Acumen developed an ultra-sensitive assay to detect total levels of sabirnetug, both bound and unbound, in CSF. The assay demonstrated sensitivity, accuracy and precision, selectivity, specificity, dilutional linearity, and stability of the method. This development will aid in the accurate quantification of total drug exposure of sabirnetug in clinical trials since only a small fraction of peripherally-administered monoclonal antibodies typically move from blood to the brain. The Phase 2 clinical trial ALTITUDE-AD (NCT06335173) is designed to evaluate the clinical efficacy and safety of sabirnetug in patients with early AD. The global study is currently enrolling at multiple investigative sites located in the United States and Canada with plans for additional sites in Europe and the UK. 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 INTERCEPT-AD (Phase 1)Completed in 2023, INTERCEPT-AD was a Phase 1, U.S.-based, multi-center, randomized, double-blind, placebo-controlled clinical trial evaluating the safety and tolerability, and establishing clinical proof of mechanism, of sabirnetug in patients with early Alzheimer’s disease (AD). Sixty-five individuals with early symptomatic AD (mild cognitive impairment or mild dementia due to AD) enrolled in this first-in-human study of sabirnetug. The INTERCEPT-AD study consisted of single-ascending-dose (SAD) and multiple-ascending-dose (MAD) cohorts and was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and target engagement of intravenous doses of sabirnetug. More information can be found on www.clinicaltrials.gov, NCT identifier NCT04931459. 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) intravenous 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 will enroll approximately 540 individuals with early Alzheimer’s disease (mild cognitive impairment or mild dementia due to AD). The global study is currently enrolling at multiple investigative sites located in the United States and Canada with plans for additional sites in Europe and the UK. 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 toxic soluble 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. 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). 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 Braunabraun@acumenpharm.com Media:Jon YuICR Westwicke AcumenPR@westwicke.com

Presentation and poster include deeper data insights on sabirnetug safety profile, target engagement and fluid biomarker changes Presentation to be featured during AAN Emerging Science Session Company on track to initiate Phase 2 trial evaluating sabirnetug in first half of 2024 CHARLOTTESVILLE, Va., April 16, 2024 (GLOBE NEWSWIRE) -- Acumen Pharmaceuticals Inc. (NASDAQ: ABOS), 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), will present the comprehensive clinical and biomarker results from its positive Phase 1 INTERCEPT-AD study of sabirnetug (ACU193) in early AD during an Emerging Science Session at the American Academy of Neurology (AAN) 2024 Annual Meeting in Denver on April 16, 2024. The results build upon Acumen’s prior presentations at the AD/PD™ 2024 Annual Meeting and positive topline data first announced in July 2023 and will be presented together for the first time with expanded analysis. A platform presentation, titled “A phase 1 study, INTERCEPT-AD, of ACU193: safety, target engagement, and biomarker changes,” will take place on Tuesday, April 16, from 6:06-6:12 PM MDT within the ES2 – Emerging Science 2 track at the Colorado Convention Center, Bluebird 1A, followed by a poster presentation with more in-depth results from 6:25-7:00 PM MDT. Sabirnetug is the first humanized monoclonal antibody to clinically demonstrate selective target engagement of AβOs, a soluble and highly toxic form of Aβ that accumulates early in AD and is an early and persistent trigger of synaptic dysfunction and neurodegeneration. Acumen is developing sabirnetug as a potential best-in-class antibody treatment for early AD. “For the first time, we’re presenting a comprehensive set of safety, biomarker and target engagement data from INTERCEPT-AD, which continue to support sabirnetug’s mechanism and potential to offer differentiated safety and efficacy as a next-generation treatment for people with early Alzheimer’s disease,” said Eric Siemers, M.D., Chief Medical Officer of Acumen and presenting author. “The results of this robust Phase 1 trial give us hope that sabirnetug could have a safety and efficacy pro could make it an attractive option for a large number of patients. We look forward to applying insights learned from INTERCEPT-AD as we embark upon our ALTITUDE-AD Phase 2 trial for sabirnetug.” Sabirnetug Demonstrated Favorable Safety and Tolerability Pro > The poster outlines that sabirnetug demonstrated a favorable safety and tolerability pro participants with early AD with a relatively low incidence of ARIA-E. There were four cases of asymptomatic ARIA-E and one symptomatic case among 48 participants who were treated with sabirnetug. Notably, none of the six participants who were APOE Ɛ4 homozygotes experienced ARIA-E despite making up 13% of all participants in the study. This contrasts with other studies of amyloid-targeting monoclonal antibodies where approximately 30 to 40 percent of participants who are APOE Ɛ4 homozygotes experienced ARIA-E. Target Engagement Sabirnetug target engagement with AβOs in cerebrospinal fluid (CSF) increased in a dose-dependent manner in both single and multiple ascending dose groups. Central target engagement approached the maximum at the highest doses of sabirnetug administered. The results suggest that at these dose levels, ACU193 concentrations approached saturation of AβOs, and suggests active removal of target from the brain. Sabirnetug Associated with Changes in CSF and Plasma Biomarkers Indicating Downstream Effects on Amyloid, pTau Species, and Synaptic Markers After Three Administrations Sabirnetug treatment also changed a number of CSF biomarkers in the multiple ascending dose cohorts, which are indicative of amyloid pathology (Aβ42/40 ratio), tau pathology (pTau181, pTau217), and synaptic injury (neurogranin, VAMP2). Sabirnetug significantly lowered CSF neurogranin (-13.9%), VAMP2 (-8.1%) and pTau181 (-13.0%) concentrations and numerically increased Aβ42/40 after three administrations of sabirnetug at 60 mg/kg once every 4 weeks (Q4W). Sabirnetug target engagement with AβOs was significantly correlated with reduction of CSF neurogranin. Additionally, plasma biomarkers for neuroinflammation (GFAP) and tau pathology (pTau181, pTau217) were lower in the 10 mg/kg Q4W and 60 mg/kg Q4W groups compared to placebo. Furthermore, nearly all patients treated with sabirnetug in the high dose multiple-ascending dose cohorts showed reductions in plaque load after three doses at 63 or 70 days. These results support sabirnetug’s proposed mechanism of action and intended target engagement of synaptotoxic AβOs. A copy of the poster and presentation will be available following the conference in the Investors section of the Company's website at . Acumen Remains On Track to Initiate Additional Clinical Studies of Sabirnetug Acumen remains on track to initiate the ALTITUDE-AD placebo-controlled Phase 2 trial of sabirnetug in the first half of 2024. Based on safety, target engagement and biomarker data from the INTERCEPT-AD trial, Acumen has determined sabirnetug doses of 35 mg/kg Q4W and 50 mg/kg Q4W in ALTITUDE-AD. This study will also evaluate long-term changes in clinical cognitive outcomes, biomarkers, and safety over 18 months. Acumen also plans to initiate a Phase 1 bioavailability study to support a subcutaneous dosing option of sabirnetug in mid-2024, as announced in November 2023. About Sabirnetug (ACU193) Sabirnetug (ACU193) is a humanized monoclonal antibody (mAb) discovered and developed based on its selectivity for soluble 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 directly address a growing body of evidence indicating that soluble AβOs are an early and persistent underlying cause of the neurodegenerative process in Alzheimer’s disease. Sabirnetug has been granted Fast Track designation for the treatment of early Alzheimer’s disease by the U.S. Food and Drug Administration. About INTERCEPT-AD INTERCEPT-AD was a Phase 1, U.S.-based, multi-center, randomized, double-blind, placebo-controlled clinical trial evaluating the safety and tolerability, and establishing clinical proof of mechanism, of sabirnetug in patients with early Alzheimer’s disease (AD). Sixty-five individuals with early AD (mild cognitive impairment or mild dementia due to AD) enrolled in this first-in-human study of sabirnetug. The INTERCEPT-AD study consisted of single-ascending-dose (SAD) and multiple-ascending-dose (MAD) cohorts and was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and target engagement of intravenous doses of sabirnetug. More information can be found on , NCT identifier NCT04931459. About Acumen Pharmaceuticals, Inc. Acumen, headquartered in Charlottesville, VA, with additional offices in Indianapolis, IN and Newton, MA, 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 toxic soluble AβOs, following positive results in INTERCEPT-AD, a Phase 1 clinical trial involving early Alzheimer’s disease patients. For more information, visit . 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 of Acumen’s product candidate, sabirnetug (ACU193), and Acumen’s preparations with respect to its plans to initiate a Phase 2 study. 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: Jon Yu ICR Westwicke AcumenPR@westwicke.com