We have identified a preclinical lead compound from Aria’s chemical library.


• The mechanism of action (MOA) of ARN2966 is currently under study and appears to be novel. ARN2966 reduces expression of APP with resultant lower production of Aβ. This potent post-transcriptional modulation of APP expression differs from other mechanisms such as inhibition of secretases. Secretase inhibitors have been pursued as disease modifying strategies by a number of pharmaceutical firms but they have encountered numerous setbacks during clinical development.


• ARN2966 is a potent post-transcriptional modulator of APP expression in transfected CHO cells that produce amyloid precursor protein (APP).


• ARN2966 is easily synthesized, bioavailable, and shows BBB penetration following oral and intravenous administration to mice.


• Proof of Concept of ARN2966’s in vivo efficacy and tolerability has been established in AD transgenic mice. ARN2966 treatment improves the memory of mice and reduces A load in the brain.


• ARN2966 and its analogues are prepared by a simple chemistry from readily available inexpensive starting materials.  Scale-up and cost of goods are not expected to be barriers to development.


• ARN2955, a newly synthesized analogue of ARN2966 has been shown to have equal potency in vitro and superior BBB penetration in mice.




Aria Neurosciences, Inc.

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Hamden, CT 06518

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Alzheimer's Disease

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