Acumen Pharmaceuticals Presents Patient Experience and Biomarker Data from Phase 1 INTERCEPT-AD Study at the Alzheimer’s Association International Conference (AAIC®) 2024

Rhea-AI Summary

Acumen Pharmaceuticals (NASDAQ: ABOS) presented new findings from its Phase 1 INTERCEPT-AD study of sabirnetug (ACU193) at the Alzheimer's Association International Conference 2024. The research focuses on patient experiences, biomarker data, and a new ultra-sensitive assay for measuring sabirnetug in cerebrospinal fluid. Sabirnetug, a humanized monoclonal antibody, targets toxic soluble amyloid beta oligomers (AβOs) in early symptomatic Alzheimer's disease (AD).

Key findings include:

• Patient interviews revealed desires for treatments that slow disease progression and maintain cognitive abilities
• Sabirnetug significantly lowered CSF levels of synaptic proteins, supporting its mechanism of action
• A new ultra-sensitive assay was developed to detect sabirnetug in CSF

Acumen is currently conducting the Phase 2 ALTITUDE-AD trial to further evaluate sabirnetug's efficacy and safety in early AD patients.

Positive

• Sabirnetug demonstrated selective target engagement of AβOs in early symptomatic AD patients
• Sabirnetug significantly lowered CSF levels of synaptic proteins, supporting its mechanism of action
• Development of an ultra-sensitive assay to detect sabirnetug in CSF, aiding in accurate quantification of drug exposure
• Ongoing Phase 2 ALTITUDE-AD trial to evaluate clinical efficacy and safety of sabirnetug

Negative

• None.

Insights

Medical Research Analyst

As a seasoned medical research analyst, I find the data presented by Acumen Pharmaceuticals on their Phase 1 INTERCEPT-AD study of sabirnetug (ACU193) for Alzheimer's disease (AD) intriguing, albeit preliminary. The focus on toxic soluble amyloid beta oligomers (AβOs) represents a novel approach in the AD treatment landscape.

Key points to consider:

• Sabirnetug's selective targeting of AβOs, which are implicated in early AD pathology, could potentially offer a more refined approach compared to broader anti-amyloid therapies.
• The lowering of CSF levels of synaptic biomarkers, particularly VAMP2, after sabirnetug administration is promising. This aligns with the drug's proposed mechanism of action and suggests potential neuroprotective effects.
• The development of an ultra-sensitive assay to detect sabirnetug in CSF is a significant technical achievement. This will be important for accurately assessing drug exposure and pharmacokinetics in future trials.

However, it's important to note that these are early-stage results. The true test of sabirnetug's efficacy will come from the ongoing Phase 2 ALTITUDE-AD trial, which will evaluate clinical outcomes over 18 months. While the biomarker data is encouraging, we must remember that many promising AD drugs have failed in later-stage trials despite showing initial biomarker improvements.

The incorporation of patient experience data is commendable and aligns with current trends in patient-centered drug development. This approach could lead to more relevant outcome measures and improved trial design in future studies.

Overall, while these results are promising, investors should remain cautiously optimistic. The AD drug development landscape is notoriously challenging and it's too early to definitively position sabirnetug as a potential "best-in-class" treatment.

Financial Analyst

From a financial perspective, Acumen Pharmaceuticals' progress with sabirnetug in the Alzheimer's disease (AD) space warrants attention, but requires careful consideration. Here's my analysis:

• Market Potential: The AD market is vast and growing, with an estimated $5.6 billion in 2021, expected to reach $13.7 billion by 2030. A successful AD drug could be extremely lucrative.
• Competitive Landscape: Recent approvals of Aduhelm (Biogen) and Leqembi (Eisai/Biogen) have set a precedent for amyloid-targeting therapies. Sabirnetug's focus on AβOs could potentially differentiate it in this crowded space.
• R&D Investment: The ultra-sensitive assay development demonstrates Acumen's commitment to robust clinical development. This could potentially streamline future trials and reduce costs.
• Risk Factors: AD drug development is notoriously risky, with a 99.6% failure rate. Sabirnetug is still in early stages and success in Phase 1 doesn't guarantee efficacy in larger trials.
• Financial Position: As of Q1 2024, Acumen had $185.5 million in cash and equivalents. This runway is important for supporting the ongoing Phase 2 trial.

Investors should view Acumen as a high-risk, high-reward opportunity. The company's focus on a novel target and patient-centric approach are positive factors, but it's competing in a challenging space against well-funded rivals. The outcome of the Phase 2 ALTITUDE-AD trial will be a critical inflection point for the company's valuation.

In the near term, I expect Acumen's stock to remain volatile, reacting to any news or data releases. Long-term potential depends entirely on sabirnetug's clinical success and ability to differentiate itself in an increasingly competitive market.

Biotech Industry Expert

As a biotech industry expert, I find Acumen Pharmaceuticals' approach with sabirnetug (ACU193) in Alzheimer's disease (AD) both innovative and strategically sound. Here's my breakdown of the key aspects:

• Target Specificity: Sabirnetug's focus on toxic soluble amyloid beta oligomers (AβOs) is a refined approach compared to broader anti-amyloid therapies. This specificity could potentially lead to improved efficacy and safety profiles.
• Biomarker Data: The reduction in synaptic biomarkers, particularly VAMP2, is encouraging. It provides early validation of sabirnetug's mechanism of action and supports the hypothesis that targeting AβOs could protect synaptic function.
• Analytical Development: The ultra-sensitive assay for detecting sabirnetug in CSF is a significant technical achievement. This tool will be important for optimizing dosing and understanding the drug's pharmacokinetics/pharmacodynamics in future trials.
• Patient-Centric Approach: Incorporating patient experience data into the drug development process is aligned with current industry best practices. This could lead to more relevant endpoints and improved trial design, potentially increasing the chances of clinical and regulatory success.

However, it's important to temper enthusiasm with caution. The AD field is littered with promising candidates that failed in late-stage trials. The ongoing Phase 2 ALTITUDE-AD trial will be the real test of sabirnetug's potential.

From an industry perspective, Acumen's positioning of sabirnetug as a potential "best-in-class" treatment is bold but not unfounded. If successful, it could capture significant market share in the wake of first-generation anti-amyloid therapies. However, execution in later-stage trials and potential differentiation from competitors will be critical for realizing this ambition.

Overall, Acumen's progress with sabirnetug represents a noteworthy development in the AD space, but as with all early-stage biotech, significant risks remain.

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 Braun
abraun@acumenpharm.com

Media:
Jon Yu
ICR Westwicke
AcumenPR@westwicke.com

FAQ

What is the purpose of Acumen Pharmaceuticals' sabirnetug (ACU193) in Alzheimer's disease treatment?

Sabirnetug is being developed as a potential best-in-class antibody treatment for early symptomatic Alzheimer's disease, targeting toxic soluble amyloid beta oligomers (AβOs) to reduce synaptic dysfunction and neurodegeneration.

What were the key findings from the Phase 1 INTERCEPT-AD study of sabirnetug (ABOS)?

The study revealed patient desires for treatments that slow disease progression, demonstrated sabirnetug's ability to lower CSF levels of synaptic proteins, and led to the development of an ultra-sensitive assay to detect sabirnetug in cerebrospinal fluid.

How does sabirnetug (ABOS) differ from other Alzheimer's treatments?

Sabirnetug is the first humanized monoclonal antibody to demonstrate selective target engagement of AβOs in early symptomatic Alzheimer's patients, potentially offering a better benefit-risk ratio compared to first-generation disease-modifying treatments.

What is the current status of sabirnetug (ABOS) clinical trials?

Acumen Pharmaceuticals is currently conducting the Phase 2 ALTITUDE-AD trial to evaluate the clinical efficacy and safety of sabirnetug in patients with early Alzheimer's disease, with ongoing enrollment in the US, Canada, and planned sites in Europe and the UK.