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Acumen Pharmaceuticals, Inc.

Direct to Brain Soluble Aβ Oligomer Selective Immunotherapy

First/Best in Class Therapy for Alzheimer’s Disease

Right Target - Right Patients - Right Delivery.  ACU-193 is Acumen’s monoclonal antibody drug candidate that targets soluble amyloid-beta oligomers (sAβo) with high affinity and selectivity.  Acumen is developing ACU-193 for direct intrathecal delivery to the brain via a device collaboration designed to increase the probability of early clinical success and enhance long term commercial potential.

The Only Alzheimer’s Immunotherapy Specifically Targeting Toxic sAβo Using Direct Brain Delivery.  ACU-193 is a late-preclinical, fully humanized monoclonal antibody that selectively targets sAβo, the primary pathologic agent in Alzheimer’s.  Composition of matter and use patents for ACU-193 run through 2030; and further IP protection is available.

Acumen is establishing an exclusive collaboration for access to FDA/CE approved chronic infusion pump systems for direct to brain drug delivery.  ACU-193 and direct brain delivery positions the program as a scientifically and clinically differentiated approach to Alzheimer’s with attractive long-term commercial and therapeutic potential.

Program Profile & Positioning

Scientific Background & Program History.  SAβo are widely recognized as the primary neurotoxins responsible for the acute cognitive deficits and progressive neurodegeneration in Alzheimer’s disease.  SAβo are non-fibrillic assemblies of Aβ peptides, and are distinct from protofibrils, fibrillar Aβ, and β-amyloid plaques.  Brain levels of sAβo are 3-8 orders of magnitude lower than levels of β-amyloid plaques or monomeric Aβ.  They are elevated in the Alzheimer’s brain, and studies suggest a correlation between levels of sAβo and cognitive deficits in Alzheimer’s.  SAβo bind with high affinity to mature synapses, most likely to a small number of highly selective neuronal receptors.  Binding to these receptors interferes with normal neuronal function leading to memory loss and neurodegeneration.  Because sAβo are present at concentrations that are 3-8 orders of magnitude lower than non-toxic monomeric and fibrillar Aβ, they are an optimal immunotherapeutic target.  However, because only approximately 0.1-0.2% of peripherally administered antibodies cross the blood-brain-barrier and reach the brain, brain exposure of peripherally administered antibodies may limit their therapeutic efficacy.  Acumen is pursuing intrathecal delivery of ACU-193 to ensure therapeutic levels of the drug candidate reach the brain and achieve effects.

Effects of sAβo.

Acumen pioneered research on sAβo.  The company’s anti-sAβo antibody program was licensed to Merck & Co. in 2003 for significant upfront and milestone payments.  ACU-193 is a third generation product of the ~8 year/~$70M partnership with Merck.  Merck advanced the program to a late preclinical development stage.  In November 2011, as part of Merck’s restructuring following its merger with Schering Plough, Acumen reacquired all rights to the program including ACU-193, backup molecules, and substantial IP with no financial or take-back rights obligations to Merck.

ACU-193 Details.  

• Humanized, affinity-matured, IgG2 monoclonal antibody with uniquely high selectivity for sAβo.

• Prevents binding of sAβo to neurons and sAβo toxic effects at synapses.

• Brain penetration, target engagement and robust biochemical and behavioral efficacy demonstrated in mouse models of Alzheimer’s.

• Excellent pharmacokinetics, bio-distribution and brain penetration demonstrated in 4 animal species.

• Excellent safety profile in exploratory studies in rhesus monkeys.

• GMP production cell lines and the necessary analytics established.

• Drug delivery collaboration with Medtronic for direct brain delivery.

• Companion diagnostic biomarker assay established.

• Composition of matter and use patent protection through 2030.

The Addario Lung Cancer Medical Institute (ALCMI), founded in 2008 as a 501c(3) non-profit organization, is a patient-centric, international research consortium driving research otherwise not possible, evidenced by ALCMI's current clinical studies CASTLE, INHERIT EGFR T790M, Genomics of Young Lung Cancer and others. ALCMI overcomes barriers to collaboration via a world-class team of investigators from 21+ institutions in the U.S., France, Italy, Spain and U.K., supported by dedicated research infrastructures such as centralized project management, tissue banks and data systems. ALCMI directly facilitates research by combining scientific expertise found at leading academic institutions with patient access through our network of community cancer centers – accelerating novel research advancements to lung cancer patients. 

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Altravax is a privately held biopharmaceutical company focused on developing first-in-class biological products to fight infectious diseases or treat other indications. The Company has a robust pipeline of candidates at various preclinical stages of development including a therapeutic vaccine against chronic hepatitis B infection. Altravax seeks investment opportunities to develop these lead candidates for clinical testing.