Drug Development/Novel Targets: Phase 2 trials

Initiate Phase 2 (proof of concept) drug trials for agents against 3-6 novel therapeutic targets. These trials will provide proof of mechanism and/or evidence of target engagement of the target being tested.

2030 PAR-14-089: Early Stage Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01) PAR-16-365: Early Stage Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01) PAR-18-175: Early Stage Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01 Clinical Trial Optional) PAR-18-877: Early Stage Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01 Clinical Trial Optional) PAS-17-064: Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R43/R44) PAS-18-187: Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R43/R44) PAS-17-065: Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R41/R42) PAS-18-188: Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R41/R42 Clinical Trial Optional) PAR-18-877: Early Stage Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01 Clinical Trial Optional) PAR-21-359: Early and Late Stage Clinical Trials for the Spectrum of Alzheimer’s Disease/Alzheimer’s Related Dementias and Age-Related Cognitive Decline (R01 Clinical Trial Optional) PAR-23-274: Seamless Early-Stage Clinical Drug Development (Phase 1 to 2a) for Novel therapeutic Agents for the Spectrum of Alzheimer's Disease (AD) and AD-related Dementias (ADRD) (UG3/UH3 Clinical Trial Required) 6.F In Progress Initiate Phase 2 (proof of concept) drug trials for agents against 3-6 novel therapeutic targets... DN 2012 AD Summit: 3A, 3B, 3F, and 5E Drug Development - Novel Targets NIA Ongoing Alzheimer’s and Related Clinical Trials and Studies A Double-blinded, Randomized, Controlled Phase 2a Safety, Proof-of-concept and Exploratory End Point Trial of the Drug LM11A-31 in Patients With Mild to Moderate Alzheimer's Disease Clinical Evaluation of T3D-959 as a Potential Disease Remedial Therapeutic for the Treatment of Alzheimer's Disease Modulation of MicroRNA Pathways by Gemfibrozil in Predementia Alzheimer Disease The delivery of essential fatty acids to the Brain in Alzheimers disease High-dose Vitamin D Supplements in Older Adults without Dementia Age-Related Mild Cognitive Impairment and novel protective role of Glutathione: implications for Alzheimer’s Disease Benfotiamine in Alzheimers Disease: A pilot study Allopregnanolone as Regenerative Therapeutic for Alzheimer's: Phase 2 Clinical Trial Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial of T3D-959 in Mild to Moderate Alzheimer's Disease A randomized, double blind, placebo-controlled study to evaluate the impact of Nilotinib treatment on safety, tolerability, pharmacokinetics and biomarkers in Dementia with Lewy Bodies (DLB) Safety and modulation of ABCC9 pathways by nicorandil for the treatment of hippocampal sclerosis of aging (SMArT–HS) Treating hyperexcitability in Alzheimer’s disease with levetiracetam to improve brain function and cognition A Seamless Phase 2A-B Randomized Double-Blind Placebo Controlled Trial to Evaluate the Efficacy and Safety of PQ 912 in Patients with Early Alzheimer's Disease Evaluating the disease-modifying potential of a sleep intervention for Alzheimer's Disease outcomes Long-term therapeutic effects of synthetic bryostatin-1 in advanced AD without memantine A randomized, placebo-controlled, double-blind study to evaluate safety and efficacy of NDX-1017 treatment in Alzheimer's dementia patients NIA-AA Symposium: Enabling Precision Medicine for Alzheimer's Disease Through Open Science Phase II trial of GM-CSF/sargramostim in Alzheimer's Disease A Proof of Concept Trial of a Sirtuin-NAD+ Activator in Alzheimer's Disease 2020

• Completion of at least six Phase 2 drug trials for agents against novel targets, providing conclusive evidence of therapeutic mechanism/target engagement. Of these at least 3 trials should be in asymptomatic, at risk individuals (e.g. FAD or ApoE4 carriers, Down syndrome, amyloid positive, type II diabetes etc.)