Mithridion focuses on potential first-in-class drugs for Alzheimer's disease (AD) that are disease-modifying treatments, as well as treatments for memory and cognitive deficits. Our drugs are designed to replace certain actions of the brain transmitter, acetylcholine, of which there is a deficit in AD, and are called "subtype-selective muscarinic agonists". They replace the actions of acetylcholine at subtypes of muscarinic receptors known to be beneficial, especially M1- and M4-subtypes of muscarinic receptors, while avoiding actions at M2- and M3-subtypes, which are know to cause side-effects. Eli Lilly & Co's research with a previous subtype-selective muscarinic agonist, xanomeline, provided strong encouragement that this class of drugs would be useful for the treatment of AD, and there is a strong hypothesis that M1 agonists are potentially disease-modifying. Unfortunately all previous first generation clinical candidates (including xanomeline) suffered from side-effects that precluded their further clinical development. We believe from extensive preclinical studies that we have solved the side-effect challenges. Scientific feedback from our Phase I clinical studies of MCD-386, our first such drug candidate, and new findings from our preclinical research, give us confidence to continue developing this class of drugs, and suggest aspects of the actions and properties of these drugs that could be improved in a next-generation drug candidate. The primary aim of the grant would be to support the preclinical development of a next generation sub-type selective muscarinic agonist for AD. An ADDF grant would greatly accelerate progress, which is currently resource constrained. We have novel drug leads in preclinical research (including very promising compounds #7-421 and #7-429). We have new in vivo models that model aspects of disease-modifying activity, with which to evaluate drug leads. We believe that, because of this good progress, we will be able within one year to accomplish the goal of selecting such a drug candidate ready to prepare for clinical development, and which we would then be able to fund with venture capital.