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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.

AdVax is an inter/multi-disciplinary team of individuals who have developed major paradigm-shifting science, research, technology and new clinical data sets demonstrating previously unidentified bacterial infections are able to translocate to the brain and be linked to the induction of Alzheimer’s disease.

We have developed novel and proprietary real time molecular diagnostics to identify these non-culturable bacteria and then apply novel immune refocusing technologies to create both monoclonal antibodies that could be used in treatments and a first of its kind vaccine for the prevention of both cardiovascular and Alzheimer’s disease.

Our program is well on its way to identifying the major disease-inducing bacteria, which are then ready to be put into the immune refocusing technology for the derivation of human monoclonal antibodies and vaccines.

Advent Life Sciences

We invest predominantly in early and mid-stage life sciences companies.  We seek to back truly innovative companies that have a first-in-class or best-in-class approach and who are looking for a well-connected partner on the road to success.

Our investments cover a range of sectors within life sciences, including new drug discovery, enabling technologies, med tech and diagnostics.Advent Life Sciences is one of Europe’s leading venture teams investing in life sciences businesses. We are a deliberately small, and highly focused team of senior individuals, with long-standing track records of entrepreneurial and investment success across the UK, Europe and the USA.

Real people. Real insight. Real value.

Innovation. Clarity. Execution.

ALIAD is the venture capital subsidiary of the Air Liquide Group (L'Air Liquide S.A.), one of the largest multinational providers of industrial and medical gases and related activities, headquartered in Paris, France. The healthcare division of the Air Liquide Group has been playing a significant role in healthcare with over €2 billion in revenue. 
ALIAD aims to promote the Group’s growth and access to innovations through taking minority stakes in innovative technology start-ups outside the Group. ALIAD can lead or co-invest with other investors. Typical allocations are made in equity and range from €1-10 million. ALIAD is currently seeking new opportunities across a wide geography, including Western Europe, North and South America and Asia.