- Cerebrospinal fluid (CSF) biomarker results are highly supportive of sabirnetug’s downstream pharmacological effects in the brain in early AD
- Poster presentation showcases method used to develop a first-of-its-kind assay to assess sabirnetug’s binding to amyloid beta oligomers (AβOs) in Alzheimer’s disease
- Company on track to initiate Phase 2 trial evaluating sabirnetug in the first half of 2024 and Phase 1 subcutaneous study in mid-2024
Acumen’s 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 triggers synaptic dysfunction and neurodegeneration. Positive topline results from 62 participants dosed in the Phase 1 INTERCEPT-AD trial (NCT04931459) were reported in
Sabirnetug (ACU193) Lowers CSF Neurogranin & pTau181 Levels in INTERCEPT-AD Study in Early AD
Several key CSF biomarkers are associated with the pathological changes that occur in AD, and evidence suggests these biomarkers may better reflect the underlying pathology of AD than imaging alone.i,ii Results from CSF samples collected before and after drug exposure in the INTERCEPT-AD study were presented and assessed for biomarkers indicative of amyloid pathology (Aβ42/40 ratio), tau pathology (pTau181, pTau217), neuronal injury (total tau) and synaptic injury (neurogranin).
Sabirnetug had an observed dose-dependent trend in the multiple ascending dose cohorts on CSF levels of pTau181, pTau217 total tau, neurogranin and the Aβ42/Aβ40 ratio, consistent with the downstream pharmacologic effects after just three administrations of the drug. Key findings include:
- Improvements in biomarkers associated with AD pathology, including significantly lowered CSF levels of neurogranin (-13.9%) and pTau181 (-13.0%) and trending toward an increasing Aβ42/40 ratio using 60 mg/kg Q4W as compared to the placebo group;
- A nominally significant correlation between target engagement of AβOs and change in neurogranin across all doses, supportive of drug effect; and
- A trend in correlation between target engagement of AβOs and change in p-tau181 across all doses, also supportive of drug effect.
These findings support a biological link between sabirnetug and neurogranin and pTau181 and are consistent with sabirnetug’s proposed mechanism of action and intended target engagement of AβOs, as sabirnetug’s effects on these two biomarkers are more closely related to binding of AβOs than plaque reduction.
“We’re thrilled to return to AD/PD this year since completing the Phase 1 INTERCEPT-AD trial with results from our biomarker assessment, which further validate our confidence in sabirnetug’s proposed mechanism of action,” said Daniel O’Connell, Chief Executive Officer of
Target Engagement in INTERCEPT-AD: Development of a Novel Assay Measuring Sabirnetug (ACU193)-Amyloid Beta Oligomer Complexes in Human CSF
Additionally,
“Despite longstanding evidence implicating soluble AβOs as a significant driver of AD pathology, historically it’s been difficult to measure and characterize this form of Aβ,” said
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 a primary 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
About INTERCEPT-AD
INTERCEPT-AD was a Phase 1,
About
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), Acumen’s preparations with respect to its plans to initiate a Phase 2 study and subcutaneous study, and Acumen’s potential to receive regulatory approval for and bring sabirnetug to patients living with AD. 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
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i Tarawneh, R. Biomarkers: Our Path Towards a Cure for Alzheimer Disease. Biomarker Insights Volume 15: 1–15. 2020.
ii Blennow K, Zetterberg H. The Past and the Future of Alzheimer's Disease Fluid Biomarkers. J Alzheimers Dis. 2018;62(3):1125-1140.
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