ATH-1105 / Athira Pharma - LARVOL DELTA

Athira Pharma to Present Data from First-in-Human Phase 1 Clinical Trial of ATH-1105 at the 4th Annual ALS Drug Development Summit (GlobeNewswire) - P1 | N=80 | NCT06432647 | Sponsor: Athira Pharma | "Athira Pharma...announced that the Company will present data from a Phase 1 clinical trial of ATH-1105 in healthy volunteers at the 4th Annual ALS drug Development Summit taking place from May 12-14, 2025....Key Highlights from the Presentation:...ATH-1105 showed a favorable safety profile and was well tolerated in both single and multiple ascending dose studies in healthy volunteers. ATH-1105 showed dose proportional pharmacokinetics and central nervous system (CNS) penetration."

P1 data • Amyotrophic Lateral Sclerosis

Athira Pharma Reports First Quarter 2025 Financial Results and Pipeline and Business Updates (GlobeNewswire) - "Completed healthy volunteer Phase 1 clinical study of ATH-1105 as a potential treatment for amyotrophic lateral sclerosis (ALS); full healthy volunteer data expected in 2H25. On-track to enable dosing ALS patients in late 2025. Athira will be presenting Phase 1 and nonclinical efficacy data for ATH-1105 for the potential treatment of ALS at the 4th Annual ALS Drug Development Summit taking place May 12-14, 2025, in Boston, Massachusetts."

New trial • P1 data • Preclinical • Amyotrophic Lateral Sclerosis

ATH-1105, a Small-molecule Positive Modulator of the Neurotrophic HGF System, is Neuroprotective in Co-culture of Human iPSC-derived Motor Neurons and Muscle (P9-11.025). (PubMed, Neurology) - "Church has received intellectual property interests from a discovery or technology relating to health care. Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff."

Journal • CNS Disorders • MET • SOD1

ATH-1105, a Small-molecule Positive Modulator of the Neurotrophic HGF System, is Neuroprotective in Co-culture of Human iPSC-derived Motor Neurons and Muscle (AAN 2025) - "Our data confirm engagement of the HGF system in the neuroprotective effects of ATH-1105 and highlight the relevance of this mechanism in human iPSC-based ALS models."

CNS Disorders • MET • SOD1

Athira Pharma Reports Full Year 2024 Financial Results and Pipeline and Business Updates (GlobeNewswire) - "ATH-1105: The study was completed in November 2024 and evaluated the safety and tolerability of ATH-1105 and included measurements of pharmacokinetic outcomes...Athira is on track to enable dosing ALS patients in 2025....Additionally, Athira paused further development of fosgonimeton, including the related open label extension clinical trial, while continuing the development of ATH-1105 and exploring partnering options."

Discontinued • Trial status • Alzheimer's Disease • Amyotrophic Lateral Sclerosis

ATH-1105-0101: A SAD and MAD Study of the Safety, Tolerability, and Pharmacokinetics of ATH-1105 (clinicaltrials.gov) - P1 | N=80 | Completed | Sponsor: Athira Pharma | Recruiting ➔ Completed

Trial completion

Athira Pharma Presents Preclinical Data Highlighting Neuroprotective Effects of ATH-1105 in Models of ALS at Motor Neurone Disease Association’s 35th International Symposium on ALS/MND (GlobeNewswire) - "Highlights of this presentation include: ATH-1105 promoted activation of MET (HGF receptor) in ALS patient-derived motor neurons​. ATH-1105 enhanced motor neuron survival and preserved neurite networks following glutamate challenge in primary rat spinal motor neurons....In a neuromuscular junction model consisting of human iPSC-derived SOD1A4V motor neurons and human muscle, ATH-1105 enhanced motor neuron survival and preserved neurite networks following glutamate challenge."

Preclinical • Amyotrophic Lateral Sclerosis

ATH-1105, a small-molecule positive modulator of the neurotrophic HGF system, is neuroprotective in co-culture of human iPSC-derived motor neurons and muscle (ALS-MND 2024) - "Rat motor neurons treated with 100 nM ATH-1105 þ glutamate exhibited a 23% increase in both neuronal survival (p < 0.05) and neurite networks (p < 0.01) compared to cultures challenged with glutamate alone. These effects coincided with a 131% increase in pMET levels (p < 0.01) in cultures treated with 100 nM ATH-1105 ± glutamate versus glutamate alone. Knockdown of the MET receptor using siRNA abolished the protective effects of ATH-1105 on neuronal survival and neurite networks."

Inflammation • MET • SOD1 • TARDBP

Athira Pharma to Present Results from Phase 2/3 LIFT-AD Clinical Trial of Fosgonimeton at the Clinical Trials on Alzheimer’s Disease (CTAD) 2024 Meeting (GlobeNewswire) - "As previously reported, topline results from the LIFT-AD trial did not achieve statistical significance for the primary endpoint of the Global Statistical Test (GST) nor its key secondary endpoints compared with placebo at 26 weeks. However, both components of GST, cognition (ADAS-Cog11) and function (ADCS-ADL23), directionally favored fosgonimeton treatment, and in pre-specified subgroups characterized by more rapid disease progression (moderate AD and APOE4 carriers), cognition and function improved or stabilized in the fosgonimeton treated group...Athira is focused on advancing the clinical development program for ATH-1105...Athira completed the first cohort of healthy volunteers in June 2024 and expects to complete the full study by year-end 2024, with a goal to begin dosing ALS patients in 2025."

P2/3 data • Trial status • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders

Athira Pharma to Focus on Advancement of ATH-1105 for the Treatment of Neurodegenerative Diseases (GlobeNewswire) - "Athira Pharma, Inc...today announced that...the Company plans to focus on advancing the clinical development program for ATH-1105 as a potential treatment for neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and AD...In alignment with Athira’s focus on continued development of ATH-1105, the Company is implementing cost containment measures including a reduction in workforce of approximately 70%. Athira expects one-time costs of approximately $2.8 million and cost savings of approximately $13.4 million on an annualized basis related to the reduction in the workforce."

Pipeline update • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders

Athira Pharma Completes First Cohort in Phase 1 Clinical Trial of ATH-1105, an Oral, Small Molecule Drug Candidate for Amyotrophic Lateral Sclerosis (ALS) (PRNewswire) - "Athira Pharma...announced that it has completed the first cohort of healthy volunteers in its ongoing, first-in-human, dose escalation Phase 1 clinical study evaluating ATH-1105, an oral, small molecule positive modulator of the neurotrophic hepatocyte growth factor (HGF) system in development for the treatment of amyotrophic lateral sclerosis (ALS)....'We are pleased to start this Phase 1 clinical trial and we are eager to explore the potential of ATH-1105 in ALS patients, which we are targeting to initiate in 2025'....The Phase 1 (NCT06432647) double-blind, placebo-controlled trial will enroll up to 80 healthy volunteers and evaluate single and multiple oral ascending doses....Completion is expected by year-end 2024."

New P1 trial • Trial status • Amyotrophic Lateral Sclerosis

A SAD and MAD Study of the Safety, Tolerability, and Pharmacokinetics of ATH-1105 (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Athira Pharma

New P1 trial

Athira Pharma Reports First Quarter 2024 Financial Results and Pipeline and Business Updates (GlobeNewswire) - "Athira expects to report topline data from LIFT-AD in the second half of 2024....Athira expects to initiate a first-in-human study of ATH-1105 in the second quarter of 2024."

New P1 trial • P2/3 data • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders

Athira Pharma Announces Upcoming Poster Presentation at American Academy of Neurology (AAN) 2024 Annual Meeting (GlobeNewswire) - "Athira Pharma, Inc...today announced a planned poster presentation at the upcoming American Academy of Neurology (AAN) 2024 Annual Meeting, to be held April 13 – 18, 2024, in Denver, Colorado and online. The presentation will highlight preclinical data supporting the continued development of Athira's pipeline of small molecule candidates targeting the neurotrophic hepatocyte growth factor (HGF) system, including fosgonimeton for Alzheimer’s disease, ATH-1105 for amyotrophic lateral sclerosis (ALS), and ATH-1020 for Parkinson’s disease."

Preclinical • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Parkinson's Disease

Targeting Neurotrophic HGF Signaling for the Treatment of Neurodegenerative Disorders (AAN 2024) - "We have developed first generation (fosgonimeton) and second generation (ATH-1020 and ATH-1105) small molecules designed to promote neurotrophic HGF system activity, with distinct properties to allow for potential therapeutic application in various neurodegenerative disorders.Design/To evaluate neurotrophic effects, primary neurons were treated with fosgonimeton, ATH-1020, or ATH-1105 and neurite outgrowth and synaptic count were measured. These results demonstrate the neurotrophic, neuroprotective, and anti-inflammatory effects of positive modulators of the HGF system. Consistent treatment effects across diverse models of neurodegenerative disorders supports the broad therapeutic potential of targeting neurotrophic HGF signaling."

Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • TARDBP

ATH-1105, a small-molecule positive modulator of the neurotrophic HGF system, is neuroprotective, preserves neuromotor function, and extends survival in preclinical models of ALS. (PubMed, Front Neurosci) - "Additionally, both early intervention (treatment initiation at 1 month of age) and delayed intervention (treatment initiation at 2 months of age) with ATH-1105 produced benefits in this preclinical model of ALS. The consistent neuroprotective and anti-inflammatory effects demonstrated by ATH-1105 preclinically provide a compelling rationale for therapeutic interventions that leverage the positive modulation of the HGF pathway as a treatment for ALS."

Journal • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • TARDBP

Athira Pharma Announces Publication in Frontiers in Neuroscience Highlighting Therapeutic Potential of ATH-1105 in Amyotrophic Lateral Sclerosis (ALS) (GlobeNewswire) - "Athira Pharma...announced publication of research highlighting the neuroprotective and anti-inflammatory effects of ATH-1105 in preclinical models of amyotrophic lateral sclerosis (ALS)....In a TDP-43 mouse model of ALS, ATH-1105 treatment significantly preserved body weight, reduced motor and nerve function decline over time, decreased plasma biomarkers of inflammation and neurodegeneration, prevented axonal degeneration and TDP-43 pathology in peripheral nerves, and ultimately extended survival....'These findings further support our plans to progress ATH-1105 into first-in-human studies in the first half of 2024'."

New trial • Preclinical • Amyotrophic Lateral Sclerosis

Athira Pharma Provides 2024 Clinical Pipeline Outlook and Business Update (StockHouse) - "LIFT-AD Phase 2/3 clinical trial of fosgonimeton in mild-to-moderate Alzheimer’s disease....The Company expects to report topline data in the second half of 2024....The initiation of first-in-human studies of ATH-1105 is targeted for the first half of 2024 to evaluate this promising drug candidate as a treatment for ALS."

New P1 trial • P2/3 data • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders

Athira Pharma Announces Upcoming Presentation at Motor Neurone Disease Association’s 34ᵗʰ International Symposium on ALS/MND (GlobeNewswire) - "Athira Pharma, Inc...today announced that a symposium presentation highlighting data from preclinical studies of ATH-1105 as a potential treatment candidate for amyotrophic lateral sclerosis (ALS) will be delivered at the upcoming Motor Neurone Disease Association (MNDA) 34th International Symposium on ALS/MND, to be held December 6 – 8, 2023 in Basel, Switzerland....'These data, which include preclinical data showing prolonged survival and demonstrating consistent improvements in motor function, nerve function, biomarkers and nerve morphology in a transgenic mouse model of ALS, strongly support confidence in our plans to advance this program into human clinical studies in the first half of 2024.'"

New trial • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders

ATH-1105, a small moleculepositive modulator of theneurotrophic hepatocyte growthfactor system, is neuroprotectivewhen administered prophylactically,therapeutically, or in combinationwith riluzole in the Prp-TDP43A315T mouse model of ALS (ALS-MND 2023) - "In the first study, ATH-1105 treatment led to signifi-cant (p<0. 05) improvements in all measured disease aspectsin the Prp-TDP43A315T mouse model of ALS. Riluzole alsodemonstrated improvements in most measures, although toa lesser degree, and had no effect on phospho-TDP43 levelsunder the conditions tested."

Combination therapy • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • Metabolic Disorders • HGF • IL6 • TARDBP • TNFA

Athira Pharma Presents Preclinical Data Further Supporting the Therapeutic Potential of ATH-1105 in Amyotrophic Lateral Sclerosis (ALS) (GlobeNewswire) - "ATH-1105 demonstrated neuroprotective properties in several preclinical models of ALS: In vitro, ATH-1105 protected motor neurons from excitotoxicity, reduced TDP-43 mis-localization, preserved metabolic stability, and maintained neuromuscular junction integrity....In vivo, treatment with ATH-1105 improved motor and nerve function, mitigated inflammation and neurodegeneration, and reduced plasma NfL and pTDP-43 accumulation in ALS mice when administered alone or in combination with riluzole."

Preclinical • Amyotrophic Lateral Sclerosis

Athira Pharma Reports Second Quarter 2023 Financial Results and Pipeline and Business Updates (GlobeNewswire) - "The Company now expects to report topline LIFT-AD results in the second half of 2024....ATH-1105 – A novel, orally available, small molecule designed to be a positive modulator of the HGF/MET system as a potential treatment candidate initially for amyotrophic lateral sclerosis (ALS)....IND-enabling studies will continue through the remainder of 2023 in order to support the potential initiation of first-in-human studies in the first half of 2024 to evaluate this promising drug candidate as a treatment for ALS."

New P1 trial • P2/3 data • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders

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 (AAIC 2023) - "The data presented provide preliminary evidence that ATH-1105 is protective against several pathological mechanisms common to FTD, including TDP-43 protein pathology, and support its continued evaluation as a therapeutic for FTD."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Frontotemporal Lobar Degeneration • Inflammation • HGF • NEFL • TARDBP

Athira Pharma Reports First Quarter 2023 Financial Results and Recent Pipeline and Business Updates (GlobeNewswire) - "'We continue to advance the Phase 2/3 LIFT-AD trial of fosgonimeton as a treatment for mild-to-moderate Alzheimer’s disease and will focus on the 40 mg dose, as the totality of the data supports the selection of this dose to enhance both our chances for success and the trial’s potential to be a registrational study'....Presented preclinical findings for ATH-1105 at AAN that demonstrated statistically significant improvements on multiple measures of 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)...Completing IND-enabling work throughout 2023 in order to initiate first-in-human studies in 2024 to evaluate this promising product candidate as a treatment for ALS."

New trial • Preclinical • Trial status • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Parkinson's Disease

Athira Pharma Presents New Clinical and Preclinical Data at the American Academy of Neurology (AAN) 2023 Annual Meeting (GlobeNewswire) - "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...'Preclinical data indicate that the neuroprotective effects of fosgonimeton are reduced in combination with donepezil, and suggest this is due, in part, to interference in AKT signaling, one of the multimodal neuroprotective mechanisms enhanced by targeting the HGF/MET system'...'We are encouraged by the compelling preclinical evidence with ATH-1105, which demonstrates statistically significant improvements on survival and nerve and motor function in an ALS animal model. We are advancing IND-enabling studies with ATH-1105 and plan to begin clinical evaluation next year'."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders