# A randomized, placebo-controlled, double-blind study to evaluate safety and efficacy of NDX-1017 treatment in Alzheimer's dementia patients > **NIH NIH R01** · ATHIRA PHARMA, INC. · 2020 · $7,811,344 ## Abstract Abstract Alzheimer’s disease (AD) is the largest unmet medical need in neurology. The patient population in the US and globally is reaching epidemic proportions due to aging societies, yet no effective treatment is available. To find a therapy that provides meaningful symptomatic relief, slows progression, and restores cellular functions, a systemic approach is needed to repair damaged cells, rebuild synapses, and restore homeostasis in the brain. Modulation of neurotrophic factor activity presents a novel strategy to counteract neurodegeneration and address multiple aspects of pathology, with the potential to improve symptoms and alter the course of disease progression. NDX-1017 is the lead clinical candidate developed by Athira Pharma, Inc., which enhances the activity of the hepatocyte growth factor (HGF) system, a potent neurotrophic and regenerative system. In in vitro studies, NDX-1017 has been shown to activate the target HGF system and induce downstream effects to promote spinogenesis and synaptogenesis, enhance long-term potentiation, and protect neurons from oxidative stress. In animal studies, NDX-1017 has been shown to restore synaptic loss, regenerate neurons, and reverse cognitive and functional impairment, in 6-OHDA model of neurodegeneration, as well as scopolamine and aged animal models of dementia. Additionally, NDX-1017 induces both acute and sustained induction in gamma power measured by quantitative electroencephalogram (qEEG) in wild-type and APP/PS1 mice, indicating CNS penetration and target engagement. The sustained qEEG effect of NDX-1017 suggests potential disease modification via structural changes in the brain. From the Phase 1 randomized, double-blind, placebo-controlled study (NCT03298672), NDX-1017 has been shown to be safe and well-tolerated at a range of therapeutically relevant doses (2-90 mg). The pharmacokinetics (PK) profile has demonstrated good consistency across animal species (i.e., rat, dog, mouse) and humans. Importantly, the functional effects observed by qEEG, i.e. acute and sustained induction in gamma power, have been replicated in humans at comparable PK exposure. In AD patients, NDX-1017 has been shown to reduce P300 latency measured by event-related potential (ERP). Together, qEEG and ERP will serve as translational biomarkers to guide dose optimization in early stage clinical trials. The proposed Phase 2 study is designed to evaluate the clinical efficacy and safety of 26-week NDX-1017 treatment in mild-to-moderate AD dementia patients. Additionally, the study is designed to demonstrate the translation of ERP biomarker and its predictive potential in cognitive outcomes, contributing knowledge to the scientific community in search of surrogate endpoints to accelerate clinical development in AD. Finally, treatment effects on CSF and plasma biomarkers of neurodegeneration and AD pathologies will be measured to understand NDX-1017’s potential to alter disease pathology. The study will provide critic... ## Key facts - **NIH application ID:** 10032566 - **Project number:** 1R01AG068268-01 - **Recipient organization:** ATHIRA PHARMA, INC. - **Principal Investigator:** Charles Bernick - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $7,811,344 - **Award type:** 1 - **Project period:** 2020-09-15 → 2023-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10032566 ## Citation > US National Institutes of Health, RePORTER application 10032566, A randomized, placebo-controlled, double-blind study to evaluate safety and efficacy of NDX-1017 treatment in Alzheimer's dementia patients (1R01AG068268-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10032566. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*