ATHIRA PHARMA, INC. Athira Pharma, Inc. announced that it is presenting new data supporting its pipeline of small molecule therapeutic candidates designed to enhance the HGF/MET neurotrophic system. The data are being presented in three poster presentations at the Alzheimer’s Association International Conference (AAIC) 2023, taking place July 16, 2023 to July 20, 2023, virtually and in Amsterdam, Netherlands. Poster Presentation (Poster 80009; Session P4-06): Biomarker analyses from the phase 2, randomized, placebo-controlled ACT-AD and open-label extension clinical trials of fosgonimeton in patients with mild-to-moderate Alzheimer’s disease.
Dr. Moebius is presenting data suggesting that improvements in plasma biomarkers of neurodegeneration (neurofilament light chain or NfL) and neuroinflammation (glial fibrillary acidic protein, or GFAP) correlate with improvements of clinical measures of cognition and function in patients with mild-to-moderate Alzheimer’s disease. This was a post-hoc analysis of the randomized, placebo-controlled Phase 2 ACT-AD study and data from the open-label extension study in patients with mild-to-moderate Alzheimer’s disease. Change from baseline in NfL and GFAP concentrations both significantly correlated with improvements in ADAS-Cog11 (Alzheimer’s Disease Assessment Scale–Cognitive Subscale).
Further, change from the double-blind period baseline in NfL concentrations significantly correlated with improvements in MMSE (Mini-Mental State Examination) scores at the transition to the open label extension study. Change from baseline in GFAP trended toward correlation with improvements in MMSE scores. NfL and GFAP improvements significantly correlate with a composite score of cognition and function, further supporting the clinical utility of these biomarkers.
Poster Presentation (Poster 79759; Session P2-05): Fosgonimeton, a small-molecule positive modulator of the HGF/MET system, attenuates amyloid-beta-mediated toxicity in primary neuron cultures. Sherif Reda, Ph.D., Associate Director, Discovery Biology, Athira Pharma, is presenting a preclinical study demonstrating that fosgonimeton attenuates amyloid-ß-mediated toxicity in vitro. Treatment with fosgonimeton reduced tau phosphorylation and protected cultured cortical neurons from amyloid-ß-induced degeneration.
Fosgonimeton drove pro-survival signaling cascades that under the conditions tested counteracted protein pathology, apoptotic signaling, oxidative stress and autophagy impairment. Results highlight fosgonimeton’s potential as a therapeutic candidate to slow disease progression and restore neuronal health. Poster Presentation (Poster 80041; Session P4-05): ATH-1105, a small-molecule positive modulator of the HGF/MET system, is neuroprotective and attenuates TDP-43 protein pathology in ALS and frontotemporal dementia-relevant preclinical models.
Jewel Johnson, Ph.D., Director, In Vivo Pharmacology, Athira Pharma, is presenting findings in preclinical models demonstrating that ATH-1105 offers protection against several pathologies common to ALS and FTD, supporting its strong therapeutic potential and continued development in these indications. The data showed that treatment with ATH-1105: Reduced markers of inflammation, neurodegeneration, and TDP-43 pathology in a mouse model of ALS and FTD; Attenuated LPS-induced cognitive impairment in vivo; Enhanced neurite outgrowth and synaptogenesis in primary rat hippocampal neurons; Protected against neurotoxic injury in primary rat cortical neurons; and Mitigated lipopolysaccharide (LPS)-stimulated cytokine release of THP-1 macrophages. The ACT-AD trial and the related open-label extension for ACT-AD participants were supported by a grant from the National Institute on Aging of the National Institutes of Health under Award Number R01AG06268.
