Athira Pharma, Inc. announced the presentation of new data from its small molecule programs enhancing the HGF/MET neurotrophic system. The data were presented in oral and poster presentations at the American Academy of Neurology (AAN) 2023 Annual Meeting taking place from April 22-27, 2023, in person in Boston, Mass. and virtually.

Oral presentation (Abstract: 4214, Program: S26.008): Fosgonimeton provides congruent improvements on neurodegeneration biomarkers, significantly correlating with composite clinical score of cognition and function in Alzheimer's disease. Dr. Moebius presented data from the completed, exploratory six month Phase 2 ACT-AD trial of fosgonimeton (ATH-1017) in mild-to-moderate Alzheimer's disease. Highlights from the oral presentation showed fosgonimeton treatment without AChEIs: Led to a significant improvement in MMSE scores from baseline (+1.6 pts, p=0.0350); Demonstrated a statistically significant decrease in plasma NfL levels compared with placebo (-6.48 pg/mL, ?p=0.0222)?; and Showed consistent and descriptive improvements compared with placebo across biomarkers of neuroinflammation (GFAP and YKL-40) and AD-specific protein pathology (Aß 42/40 ratio and p-Tau181).

In the full study population, statistically significant associations were observed between change from baseline (CFB) of a composite measure of cognition and function and CFB in neurofilament light chain (NfL, an established biomarker of neurodegeneration, p=0.0023), and GFAP (a biomarker of neuroinflammation, p=0.0402). Oral presentation (Abstract 3944, Program: S14.008): “Therapeutic Potential of Fosgonimeton, a Small-Molecule Positive Modulator of the Neurotrophic HGF/MET Pathway, in Neurodegenerative Conditions. Dr. Church reviewed compelling preclinical data that continue to elucidate fosgonimeton's multimodal mechanism of action and therapeutic potential in neurodegenerative diseases, including: Neurotrophic effects demonstrated by an increase in synaptogenesis and neurite length in hippocampal and cortical neurons, respectively; Neuroprotective effects on cortical neurons subjected to various neurotoxic insults, including oxidative stress, neuroinflammation, excitotoxicity, and mitochondrial dysfunction; Reduced protein pathology including Aß-induced p-tau accumulation in cortical neurons and 6-OHDA–induced a-synuclein aggregation in dopaminergic neurons; and Improved function in several animal models including an LPS-induced neuroinflammation model of cognitive impairment and a model of 6-OHDA–induced motor deficits.

Poster presentation (Abstract 3277, Program P08.007): Small Molecule Positive Modulator of Hepatocyte Growth Factor (HGF)/MET, ATH-1105, Improves Function and Reduces Disease Biomarkers in a TDP-43 Mouse Model of Amyotrophic Lateral Sclerosis. Preclinical findings with ATH-1105 demonstrated statistically significant improvements on nerve and motor function, biomarkers of inflammation and neurodegeneration, and survival in an animal model of amyotrophic lateral sclerosis (ALS), including: Prolonged survival and delayed time to first mortality (p=0.0035); Improvement in balance, coordination, and muscle strength in motor function tests (p<0.0001); Protection against body weight reduction (p<0.01); Preservation of nerve function and structure (p<0.001); and Reduction of plasma biomarkers of systemic inflammation and neurodegeneration (p<0.0001).