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Innovative Pilot Studies of Novel Mechanism of Action Compounds

NAMHC Concept Clearance


Lois Winsky, Ph.D.
Chief, Molecular Cellular and Genomics Neuroscience Research Branch
Division of Neuroscience and Basic Behavioral Science (DNBBS)


This initiative will support innovative Phase I and Phase IIa studies of compounds of potential neurobiological relevance with novel mechanisms of action. The initiative encourages a broad approach for exploring pharmacological and functional effects of compounds, in the context of standard outcome measures. Such approaches will provide early proof-of-concept testing of clinically relevant neurobiological outcomes, and de-risk promising drug candidates.


There is a critical need to accelerate the development and testing of novel treatments for mental disorders. This need is intensified by the poor success and approval rate of new drugs for central nervous system disorders and the departure of pharmaceutical companies from psychiatric therapeutic development. This initiative will address this need by supporting experimental medicine-based Phase I and Phase IIa studies. Phase I studies (first-in-human pharmacology experiments) will assess target engagement, pharmacological or physiological effect, safety, and tolerability of novel compounds in order to build a pipeline for initial Phase II testing or efficacy trials. Phase IIa proof-of-concept studies of novel compounds will use pharmacologically based dosing, with assessment of target engagement and impact on clinically relevant physiological systems. The objective of the initiative is to facilitate Phase IIa and proof-of-concept studies, as well as rapid collection of data, in order to "de-risk" novel mechanism of action or combination treatments and thereby attract private funding for further clinical and commercial development.

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