Athira Pharma Announces Publication of Preclinical Data Highlighting Fosgonimeton Treatment in Models of Alzheimer’s Disease

Fosgonimeton counteracts mechanisms of amyloid-beta (Aβ)-driven toxicity and demonstrates neuroprotection in preclinical models of Alzheimer’s disease

BOTHELL, Wash., April 11, 2024 (GLOBE NEWSWIRE) -- Athira Pharma, Inc. (NASDAQ: ATHA), a late clinical-stage biopharmaceutical company focused on developing small molecules to restore neuronal health and slow neurodegeneration, today announced the publication of preclinical data supporting the therapeutic potential of fosgonimeton in Alzheimer’s disease. The original research article, “Fosgonimeton Attenuates Amyloid-Beta Toxicity in Preclinical Models of Alzheimer’s Disease,” authored by Reda, S., et al., was published in the peer-reviewed journal, Neurotherapeutics. Fosgonimeton is a potentially first-in-class, once daily, subcutaneously administered small molecule drug candidate designed to enhance the neurotrophic hepatocyte growth factor (HGF) system, and is in development for neurodegenerative disorders, including Alzheimer’s disease.

“These data continue to highlight the potential of fosgonimeton as a novel therapeutic approach for Alzheimer's disease targeting multiple facets of its complex pathophysiology,” said Kevin Church, Ph.D., Chief Scientific Officer of Athira. “By positively modulating the HGF signaling system, fosgonimeton demonstrated neuroprotective and neurotrophic effects, countering mechanisms of amyloid-beta (Aβ)-induced toxicity both in vitro and in vivo. Our preclinical findings describe several mechanisms by which fosgonimeton may disrupt the neurodegenerative cascade of Alzheimer’s disease downstream of Aβ toxicity, including reduction of mitochondrial oxidative stress and excitotoxicity, improvement of autophagic pathway function, and attenuation of tau hyperphosphorylation.”

Key findings reported in the study publication regarding fosgonimeton in preclinical models of Alzheimer’s disease include:

• In primary rat cortical neurons challenged with Aβ, fosgonimeton treatment improved neuronal survival, protected neurite networks, and reduced tau hyperphosphorylation following Aβ injury.
• Fosgonimeton attenuated Aβ-induced mitochondrial stress and apoptotic signaling.
• Fosgonimeton enhanced activation of pro-survival effectors extracellular signal-regulated kinase (ERK) and protein kinase B (AKT). It also reduced activity of glycogen synthase kinase 3 beta (GSK3β), one of the main kinases involved in tau hyperphosphorylation.
• Fosgonimeton mitigated Aβ-induced deficits in Unc-like kinase 1 (ULK1) and Beclin-1 expression, suggesting a potential effect on autophagy.
• Fosgonimeton improved cognitive performance in an Aβ rat model of Alzheimer’s disease.