PD2024, PD2015 and PD2244: Frontotemporal Dementia
P2D has developed a series of potent, centrally acting anti-inflammatory drugs for the treatment of Frontotemporal Dementia (FTD), a designated orphan disease. These compounds are orally active. Their mechanism of action is inhibition of tumor necrosis factor-alpha (TNFα) via blockade of TNFα synthesis by inhibition of TNFα mRNA. As these TNFα inhibitors decrease both central and plasma TNFα levels, plasma TNFα levels may therefore serve as a target to titrate PD2024/2015 doses to insure adequate target engagement in preclinical and clinical studies. In 3xTgFTD/AD mouse models the compounds block the development of FTD tau-inclusion bodies and block the development of cognitive and behavior deficits in this 3xTg knock-in P301L tau preclinical FTD transgenic model. PD2024 and PD2015 treatment also blocked the development of disease-associated CNS inflammation measured by microglial activation. Therefore, PD2024 and PD2015 both appeared to be disease-modifying agents. P2D’s TNFα inhibitors are currently in non-GLP preclinical safety/tox studies.
PD3044 and analogs: Attention Deficit Hyperactivity Disorder