A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-Fosgonimeton (ATH-1017) Following a Single Subcutaneous Dose in Healthy Male Subjects

This is a Phase 1, open-label, nonrandomized, single-dose human, absorption, metabolism, and excretion study of [14C]-Fosgonimeton

Start Date13 Jul 2022

Sponsor / Collaborator

Athira Pharma, Inc.

[+2]

NCT04831281 / CompletedPhase 2

A Randomized, Placebo-Controlled, Double-Blind Study of ATH-1017 Treatment in Subjects With Parkinson's Disease Dementia or Dementia With Lewy Bodies

This study is designed to evaluate the safety and treatment effects of fosgonimeton (ATH-1017) in subjects with Parkinson's Disease Dementia or Dementia with Lewy Bodies, with a randomized treatment duration of 26 weeks.

Start Date20 Jan 2022

Sponsor / Collaborator

Athira Pharma, Inc.

NCT04886063 / Active, not recruitingPhase 2/3

Open-Label Extension of Studies ATH-1017-AD-0201 and ATH-1017-AD-0202 in Subjects With Mild to Moderate Alzheimer's Disease

The objective of this study is to determine the safety and tolerability of fosgonimeton (ATH-1017) in subjects with mild to moderate Alzheimer's disease who completed the 26-week randomized treatment in Study ATH-1017-AD-0201 or Study ATH-1017-AD-0202.

Start Date30 Jun 2021

Sponsor / Collaborator

Athira Pharma, Inc.

100 Clinical Results associated with Fosgonimeton

100 Translational Medicine associated with Fosgonimeton

100 Patents (Medical) associated with Fosgonimeton

Literatures (Medical) associated with Fosgonimeton

01 Jul 2024·Neurotherapeutics

Fosgonimeton attenuates amyloid-beta toxicity in preclinical models of Alzheimer's disease

Article

Author: Reda, Sherif M ; Berthiaume, Andrée-Anne ; Moebius, Hans J ; Taylor, Robert W ; Stein, Liana R ; Church, Kevin J ; Wu, Wei ; Johnston, Jewel L ; Setti, Sharay E

Positive modulation of hepatocyte growth factor (HGF) signaling may represent a promising therapeutic strategy for Alzheimer's disease (AD) based on its multimodal neurotrophic, neuroprotective, and anti-inflammatory effects addressing the complex pathophysiology of neurodegeneration. Fosgonimeton is a small-molecule positive modulator of the HGF system that has demonstrated neurotrophic and pro-cognitive effects in preclinical models of dementia. Herein, we evaluate the neuroprotective potential of fosgonimeton, or its active metabolite, fosgo-AM, in amyloid-beta (Aβ)-driven preclinical models of AD, providing mechanistic insight into its mode of action. In primary rat cortical neurons challenged with Aβ (Aβ_1-42), fosgo-AM treatment significantly improved neuronal survival, protected neurite networks, and reduced tau hyperphosphorylation. Interrogation of intracellular events indicated that cortical neurons treated with fosgo-AM exhibited a significant decrease in mitochondrial oxidative stress and cytochrome c release. Following Aβ injury, fosgo-AM significantly enhanced activation of pro-survival effectors ERK and AKT, and reduced activity of GSK3β, one of the main kinases involved in tau hyperphosphorylation. Fosgo-AM also mitigated Aβ-induced deficits in Unc-like kinase 1 (ULK1) and Beclin-1, suggesting a potential effect on autophagy. Treatment with fosgo-AM protected cortical neurons from glutamate excitotoxicity, and such effects were abolished in the presence of an AKT or MEK/ERK inhibitor. In vivo, fosgonimeton administration led to functional improvement in an intracerebroventricular Aβ_25-35 rat model of AD, as it significantly rescued cognitive function in the passive avoidance test. Together, our data demonstrate the ability of fosgonimeton to counteract mechanisms of Aβ-induced toxicity. Fosgonimeton is currently in clinical trials for mild-to-moderate AD (NCT04488419; NCT04886063).

01 Mar 2024·Psychiatry and Clinical Neurosciences Reports

Beyond lecanemab: Examining Phase III potential in Alzheimer's therapeutics

Article

Author: Osaka, Hitoshi ; Nishida, Keiichiro ; Kanazawa, Tetsufumi

AbstractThis review focuses on the development of therapeutic interventions for Alzheimer's dementia. While established treatments targeted acetylcholine and NMDA receptors, there is a growing demand for innovative therapies as the aging population increases. The paper highlights the US Food and Drug Administration's approval of aducanumab (Aduhelm) and lecanemab (Leqembi), emphasizing the developmental status of new treatments. Specifically, it covers seven principal drugs in Phase III trials, detailing their mechanisms of action, clinical trial specifics in the United States and Japan, and the current status of regulatory applications. The review focuses on amyloid removal (donanemab), tau protein mitigation (E2814), drug repositioning (Semaglutide, GV1001), and disease‐modifying small molecules (fosgonimeton, hydralazine, masitinib). However, Gantenerumab and Solanezumab, unsuccessful in Phase III, are not covered. While the future approval status remains uncertain, we hope these drugs will offer beneficial therapeutic effects for potential dementia patients.

01 Oct 2023·Current Neurology and Neuroscience Reports

Lewy Body Dementia: An Overview of Promising Therapeutics

Review

Author: Sha, Sharon J ; Skylar-Scott, Irina A

PURPOSE OF REVIEWLewy body dementia (LBD) encompasses dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). This article will emphasize potential disease-modifying therapies as well as investigative symptomatic treatments for non-motor symptoms including cognitive impairment and psychosis that can present a tremendous burden to patients with LBD and their caregivers.RECENT FINDINGSWe review 11 prospective disease-modifying therapies (DMT) including four with phase 2 data (neflamapimod, nilotinib, bosutinib, and E2027); four with some limited data in symptomatic populations including phase 1, open-label, registry, or cohort data (vodabatinib, ambroxol, clenbuterol, and terazosin); and three with phase 1 data in healthy populations (Anle138b, fosgonimeton, and CT1812). We also appraise four symptomatic therapies for cognitive impairment, but due to safety and efficacy concerns, only NYX-458 remains under active investigation. Of symptomatic therapies for psychosis recently investigated, pimavanserin shows promise in LBD, but studies of nelotanserin have been suspended. Although the discovery of novel symptomatic and disease-modifying therapeutics remains a significant challenge, recently published and upcoming trials signify promising strides toward that aim.

News (Medical) associated with Fosgonimeton

22 Oct 2024

·www.globenewswire.com

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

BOTHELL, Wash., Oct. 22, 2024 (GLOBE NEWSWIRE) -- Athira Pharma, Inc. (NASDAQ: ATHA), a clinical stage biopharmaceutical company focused on developing small molecules to restore neuronal health and slow neurodegeneration, today announced that results from the Phase 2/3 LIFT-AD clinical trial of fosgonimeton to treat Alzheimer’s disease (AD) will be presented at the 17th Annual Clinical Trials on Alzheimer’s Disease (CTAD) taking place October 29 - November 1, 2024, in Madrid, Spain. Presentation Details: Title: Fosgonimeton for the Treatment of Alzheimer’s Disease; Efficacy and Safety Results from the LIFT-AD TrialSession: Oral Communications: OC2 Date/Time: Tuesday, October 29 at 5:10 p.m., CETPresenter: Anton P. Porsteinsson, M.D., Director of the University of Rochester Alzheimer’s Disease Care, Research, and Education Program (AD-CARE) and a LIFT-AD investigator 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. In addition, data across biomarkers of protein pathology (Aβ42/40, p-Tau181, and p-Tau217), inflammation (GFAP) and neurodegeneration (NfL) showed directional changes in favor of fosgonimeton treatment that are consistent with the broad neuroprotective mechanism of HGF modulation. “We believe the totality of the data supports the potential of HGF modulation for the treatment of neurodegenerative diseases,” said Javier San Martin, M.D., Chief Medical Officer of Athira. Athira is focused on advancing the clinical development program for ATH-1105, a novel, oral, next-generation small molecule positive modulator of the neurotrophic hepatocyte growth factor (HGF) system, as a potential treatment for neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Athira is conducting a first-in-human Phase 1 (NCT 06432647) double-blind, placebo-controlled trial that is enrolling up to 80 healthy volunteers. The study is evaluating the safety and tolerability of ATH-1105 and includes measurements of pharmacokinetic outcomes. 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. About Athira Pharma, Inc. Athira Pharma, Inc., headquartered in the Seattle, Washington area, is a clinical-stage biopharmaceutical company focused on developing small molecules to restore neuronal health and slow neurodegeneration. Athira aims to alter the course of neurological diseases by advancing its pipeline of drug candidates that modulate the neurotrophic HGF system. For more information, visit www.athira.com. You can also follow Athira on Facebook, LinkedIn, X (formerly known as Twitter) and Instagram. Forward-Looking Statements This communication contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact and include statements regarding: Athira’s drug candidates as potential treatments for Alzheimer’s disease, amyotrophic lateral sclerosis, and other neurodegenerative diseases; future development plans; the anticipated timing of its ongoing clinical trials and planned clinical trials; the potential learnings from preclinical studies and other nonclinical data, the LIFT-AD trial, and the ongoing Phase 1 trial of ATH-1105 and their ability to inform and improve future clinical development plans; expectations regarding the potential efficacy and commercial potential of Athira’s drug candidates and regarding the safety and tolerability of ATH-1105; Athira’s ability to advance its drug candidates into later stages of development; Athira’s planned focus on the development of ATH-1105 for the treatment of amyotrophic lateral sclerosis; the ability to advance product candidates into later stages of development; and other information that is not historical information. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “on track,” “would,” “expect,” “plan,” “believe,” “intend,” “pursue,” “continue,” “suggest,” “potential,” “target” and similar expressions. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the data from preclinical and clinical trials may not support the safety, efficacy and tolerability of Athira’s drug candidates; development of drug candidates may cease or be delayed; regulatory authorities could object to protocols, amendments and other submissions; future potential regulatory milestones for drug candidates, including those related to current and planned clinical studies, may be insufficient to support regulatory submissions or approval; Athira may not be able to recruit sufficient patients for its clinical trials; the outcome of legal proceedings that have been or may in the future be instituted against Athira, its directors and officers; possible negative interactions of Athira's drug candidates with other treatments; Athira’s assumptions regarding its financial condition and the sufficiency of its cash, cash equivalents and investments to fund its planned operations may be incorrect; adverse conditions in the general domestic and global economic markets; the impact of competition; the impact of new or changing laws and regulations; Athira may be unable to enter into new partnerships, financings or collaborations; as well as the other risks detailed in Athira’s filings with the Securities and Exchange Commission from time to time. These forward-looking statements speak only as of the date hereof and Athira undertakes no obligation to update forward-looking statements. Athira may not actually achieve the plans, intentions, or expectations disclosed in its forward-looking statements, and you should not place undue reliance on the forward-looking statements. Investor & Media Contact: Julie Rathbun Athira Pharma Julie.rathbun@athira.com 206-769-9219 Corporate Development Contact:Maya KneipProgram Manager, Portfolio & Program ManagementMaya.kneip@athira.com (206) 412-9078

Clinical ResultPhase 1

23 Sep 2024

·www.biospace.com

Athira Pharma to Lay Off 70% of Workforce

iStock, simplehappyart Athira Pharma will cut about 49 positions, including two people in the C-suite. The announcement follows the company’s disappointing results for its investigational Alzheimer’s therapy. Athira Pharma will lay off about 70% of its workforce as part of cost-containment measures, the company has announced . The clinical-stage biopharma based in Bothell, Washington, expects its cuts of about 49 positions to be mostly complete by Dec. 31, according to an SEC filing . Those being laid off include Andrew Gengos, chief business officer and chief financial officer, and Rachel Lenington, chief operating officer and chief development officer, with both executives’ terminations effective Oct. 1. The announcement comes shortly after Athira shared that its investigational injection fosgonimeton failed to significantly boost cognition or function in patients with mild to moderate Alzheimer’s disease in the Phase II/III LIFT-AD trial. In its Sept. 17 announcement noting the layoffs, Athira said it will focus on advancing clinical development of ATH-1105 as a potential treatment for neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). ATH-1105 is in a Phase I trial, with completion expected by end of the year, according to the company. It plans to start dosing ALS patients in 2025. 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 workforce reduction, according to the announcement. It noted that due to those cost-containment measures and based on its operating plan, it should be able to extend its cash runway into the first quarter of 2026. The company said it will also consider various options including partnering and financing with the intention to extend its cash runway to obtain initial proof of concept and enable further development for ATH-1105 in neurodegenerative diseases.

Phase 1Phase 2

20 Sep 2024

·www.fiercebiotech.com

After Alzheimer's stumble, Athira lays off 70% of workforce and pivots to ALS small molecule

Athira Pharma is pivoting from fosgonimeton to ATH-1105, an oral small molecule candidate for amyotrophic lateral sclerosis. Athira Pharma has been on a bumpy road in recent years, and, now, the company is restructuring and shedding weight to try to keep the journey going. Just a couple of weeks after announcing that its Alzheimer’s disease candidate fosgonimeton failed to beat placebo in a phase 2/3 trial, Athira is laying off 70% of its staff and saying goodbye to several executives. The biotech is pivoting to focus on ATH-1105, an oral small molecule for amyotrophic lateral sclerosis (ALS).“We are encouraged about the potential for ATH-1105, as this oral, next-generation HGF-modulating drug candidate has enhanced blood-brain-barrier penetration and improved pharmacokinetic properties,” Athira President and CEO Mark Litton, Ph.D., said in a Sept. 17 release.The layoffs are expected to affect about 49 employees and will cost Athira about $2.8 million in the near term while leading to savings of approximately $13.4 million on an annual basis. The moves are expected to extend the company’s cash runway to the first quarter of 2026, Athira said in the release.As part of the workforce reduction and restructuring, Athira is also laying off Andrew Gengos, chief business officer and chief financial officer, and Rachel Lenington, chief operating officer and chief development officer, effective Oct. 1, according to a Securities and Exchange Commission filing. Also on that date, the company’s vice president of finance, Robert Renninger, will take over as principal financial officer and principal accounting officer. In 2021, former Athira CEO Leen Kawas, Ph.D., was accused of altering images in multiple research papers she published from work done at Washington State University. Kawas was dismissed later that year and replaced by Litton.Athira published data earlier this year showing that ATH-1105 decreased pathological protein accumulation in the sciatic nerve of mice with ALS. The Washington-based biotech is now conducting a first-in-human phase 1 trial with the molecule, which should begin dosing ALS patients in early 2025, according to the release.

Phase 1Executive Change

100 Deals associated with Fosgonimeton

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 3	US	Athira Pharma, Inc.	28 Sep 2020
Dementia due to Parkinson's disease	Phase 2	US	Athira Pharma, Inc.	20 Jan 2022
Lewy Body Disease	Phase 2	US	Athira Pharma, Inc.	20 Jan 2022

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04488419 (LIFT-AD, Biospace) Manual	Phase 2/3	Alzheimer Disease	312	Fosgonimeton	foxnzzzvqn(vbqpsziwgr) = oacjkvaabg cjettnwbsx (rplljwffgn ) View more	Negative	03 Sep 2024
				Placebo	(trsjaragmo) = kpnosxghot iqkxethqoy (tuyflkejfc ) View more
NCT04831281 (SHAPE, GlobeNewswire) Manual	Phase 2	Dementia due to Parkinson's disease \| Lewy Body Disease	28	Fosgonimeton	(kyeqlsfnvx) = a composite score of the change in Event-Related-Potential (ERP) P300 latency and cognitive assessment (ADAS-Cog13), was not met compared with placebo rwxcnnhmpb (hxfgbnwxew ) Not Met View more	Negative	12 Dec 2023
				Placebo
NCT04491006 (ACT-AD, CTgov)	Phase 2	Alzheimer Disease	77	Placebo	buyeiengfe(ohpdjaoayy) = howraceyrt rqqgfiubii (ljptjicikz, obnajpydcy - cjpeewieei) View more	-	12 Jun 2023
AAIC2022	Not Applicable	-	-	Fosgonimeton	kuzuxaxhth(vzbmbqwfgc) = efcruonzky eczatbwyiu (egcvqxfytv )	-	20 Dec 2022
NCT04491006 (ACT-AD, GlobeNewswire) Manual	Phase 2	Alzheimer Disease	77	Fosgonimeton	ymrdtkfaqy(utaervcuvq) = zecbwumyle sfqjwoashg (jygehqetjk ) View more	Negative	22 Jun 2022
				Placebo	-

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