In 1998, Acumen’s founders published a nice review articulating the different therapeutic approaches that might stop ADDLs.  Acumen has pursued two approaches: immunotherapy and small molecule therapeutics.

Immunotherapy approaches – both passive and active – have been licensed to Merck who are actively bringing an anti-ADDL antibody towards the clinic.  Merck also holds an exclusive option to anti-ADDL vaccines.

Acumen remains independently focused on anti-ADDL small molecules. Specifically, we have an Assembly Blocker and Binding Inhibitor programs.  The goal of the Assembly Blocker program is to stop the formation of neurotoxic oligomers. This is a difficult challenge, since it requires a small organic molecule to stop a protein-protein interaction.  Common wisdom says this is not a prudent target. However, recent publications demonstrate that the pharmaceutical and biotech world may need to rethink this lore:  there are certain protein-protein interactions which have proven to be tractable small molecule targets.  ADDLs fit the emerging characteristics of such tractable problems.  Further, Acumen’s progress has demonstrated that selective, potent small molecules can and do stop ADDL assembly. This program is in development now.

The second program seeks Binding Inhibitors.  The goal of this program is to stop ADDLs from binding to neurons. There are two mechanisms which may work: bind to ADDLs at the location where they bind to neurons (a reverse antagonist) and binding to the receptor in a manner which allow their continued function, but occupies the ADDL docking site (receptor antagonist).  This target falls in the bulls eye of traditional pharmacology and represents a “classic” though difficult program.