latozinemab (GSK4527223) / GSK 
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  • ||||||||||  latozinemab (GSK4527223) / GSK
    Journal:  An anti-sortilin affibody-peptide fusion inhibits sortilin-mediated progranulin degradation. (Pubmed Central) -  Aug 26, 2024   
    Our results introduce A3-PGRNC15* as a promising new agent with therapeutic potential for the treatment of frontotemporal dementia. Furthermore, the work highlights means to increase binding affinity through synergistic contribution from two orthogonal polypeptide units.
  • ||||||||||  latozinemab (GSK4527223) / GSK
    Discovery of IGFBPL1-fusion Proteins as Multifunctional Therapeutics for Retinal Degenerative Disorders (MCP Hall A) -  Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_2242;    
    Collectively, these observations support the further development of IGFBPL1-derived therapeutics for retinal degenerative disorders. Our results are one of the first to reduce to practice the potent pharmacology of a multifunctional, multi-targeting therapeutic for neurodegenerative disease.
  • ||||||||||  latozinemab (GSK4527223) / GSK
    P1 data, Journal:  Phase 1 study of latozinemab in progranulin-associated frontotemporal dementia. (Pubmed Central) -  Feb 15, 2024   
    Our results are one of the first to reduce to practice the potent pharmacology of a multifunctional, multi-targeting therapeutic for neurodegenerative disease. Data from the first-in-human phase 1 study support further development of latozinemab for the treatment of FTD-GRN.
  • ||||||||||  latozinemab (GSK4527223) / GSK
    Enrollment status:  Continuation Study for Latozinemab (clinicaltrials.gov) -  Dec 20, 2023   
    P3,  N=35, Enrolling by invitation, 
    Data from the first-in-human phase 1 study support further development of latozinemab for the treatment of FTD-GRN. Recruiting --> Enrolling by invitation
  • ||||||||||  latozinemab (GSK4527223) / GSK
    Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date:  A Phase 3 Study to Evaluate Efficacy and Safety of AL001 in Frontotemporal Dementia (INFRONT-3) (clinicaltrials.gov) -  Nov 3, 2023   
    P3,  N=110, Active, not recruiting, 
    Recruiting --> Enrolling by invitation Recruiting --> Active, not recruiting | N=180 --> 110 | Trial completion date: Dec 2023 --> Oct 2027 | Trial primary completion date: Oct 2023 --> Sep 2025
  • ||||||||||  latozinemab (GSK4527223) / GSK
    New P3 trial:  Continuation Study for Latozinemab (clinicaltrials.gov) -  Oct 31, 2023   
    P3,  N=35, Recruiting, 
  • ||||||||||  latozinemab (GSK4527223) / GSK
    Enrollment change, Trial completion date, Trial termination, Trial primary completion date:  A Phase 2 Study to Evaluate AL001 in C9orf72-Associated ALS (clinicaltrials.gov) -  Jun 18, 2023   
    P2,  N=5, Terminated, 
    Registered on 17 August 2018, https://clinicaltrials.gov/ct2/show/NCT03636204 . N=45 --> 5 | Trial completion date: Feb 2023 --> Oct 2022 | Active, not recruiting --> Terminated | Trial primary completion date: Feb 2023 --> Oct 2022; The Sponsor is considering a subsequent study in ALS, potentially with different inclusion/exclusion criteria.
  • ||||||||||  latozinemab (GSK4527223) / GSK
    Review, Journal:  Progranulin as a therapeutic target in neurodegenerative diseases. (Pubmed Central) -  Jul 23, 2022   
    Mutations that reduce PGRN levels increase the risk for developing Alzheimer's disease, Parkinson's disease, and limbic-predominant age-related transactivation response DNA-binding protein 43 encephalopathy, as well as exacerbate the progression of amyotrophic lateral sclerosis (ALS) and FTD caused by the hexanucleotide repeat expansion in the C9orf72 gene. Elevating and/or restoring PGRN levels is an attractive therapeutic strategy and is being investigated for neurodegenerative diseases through multiple mechanisms of action.
  • ||||||||||  latozinemab (GSK4527223) / GSK
    Enrollment closed, Trial completion date, Trial primary completion date:  A Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2) (clinicaltrials.gov) -  Jul 1, 2022   
    P2,  N=40, Active, not recruiting, 
    Elevating and/or restoring PGRN levels is an attractive therapeutic strategy and is being investigated for neurodegenerative diseases through multiple mechanisms of action. Recruiting --> Active, not recruiting | Trial completion date: May 2023 --> Jun 2026 | Trial primary completion date: Mar 2023 --> Jan 2026
  • ||||||||||  latozinemab (GSK4527223) / GSK
    Enrollment closed:  A Phase 2 Study to Evaluate AL001 in C9orf72-Associated ALS (clinicaltrials.gov) -  Apr 14, 2022   
    P2,  N=45, Active, not recruiting, 
    Recruiting --> Active, not recruiting | Trial completion date: May 2023 --> Jun 2026 | Trial primary completion date: Mar 2023 --> Jan 2026 Recruiting --> Active, not recruiting
  • ||||||||||  AL001 / GSK
    Journal:  Theoretical insights into the adsorption mechanism of Cd(II) on the basal surfaces of kaolinite. (Pubmed Central) -  Aug 17, 2021   
    Representative monodentate and bidentate Cd(II) complexes were constructed on the Kln-Al(001) and Kln-Si(001̅) surfaces...Furthermore, radial distribution functions supported by AIMD simulations were employed to confirm the structural features of Cd(II) coordination shell at kaolinite-water interfaces. This theoretical study provides insightful guidance for future Cd(II) research to improve current assessments of contaminant remediation.
  • ||||||||||  AL001 / GSK
    Update on the Phase 2 Study of AL001 in Frontotemporal Dementia Patients Carrying a Granulin Mutation () -  Aug 7, 2021 - Abstract #CTAD2021CTAD_108;    
    AL001 is being developed for the treatment of FTD-GRN to reduce the rate of neurodegeneration by increasing levels of PGRN and disrupting the pathophysiological disease cascade associated with FTD-GRN. INFRONT-3 is an ongoing, pivotal Phase 3 study to evaluate if AL001 can slow or stop disease progression in carriers of GRN mutations.
  • ||||||||||  AL001 / Alector
    [VIRTUAL] AL001 Blocks the Sortilin/PGRN Interaction and is a Potential Therapy for FTD-GRN () -  Mar 18, 2021 - Abstract #AAN2021AAN_145;    
    INFRONT-3 is an ongoing, pivotal Phase 3 study to evaluate if AL001 can slow or stop disease progression in carriers of GRN mutations. AL001 is being developed for the treatment of carriers of GRN mutations causative of FTD to reduce the rate of neurodegeneration by increasing levels of PGRN in the periphery and the brain.
  • ||||||||||  latozinemab (GSK4527223) / GSK
    Trial completion date, Trial primary completion date:  A Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2) (clinicaltrials.gov) -  Sep 2, 2020   
    P2,  N=40, Recruiting, 
    AL001 is being developed for the treatment of carriers of GRN mutations causative of FTD to reduce the rate of neurodegeneration by increasing levels of PGRN in the periphery and the brain. Trial completion date: Nov 2021 --> May 2023 | Trial primary completion date: Nov 2021 --> Mar 2023
  • ||||||||||  AL001 / Alector
    [VIRTUAL] PK/PD MODEL OF THE EFFECTS OF THE ANTI- SORTILIN ANTIBODY AL001 IN HUMANS () -  Aug 10, 2020 - Abstract #CTAD2020CTAD_137;    
    Diagnostic plots, including visual predictive checks, show the model was predictive of the effect of AL001 on Sortilin expression on WBCs and PGRN levels in plasma and in CSF. Simulations were run for various regimens to inform dosing choice in clinical trials aimed at determining the efficacy of AL001 in patients with FTD-GRN.
  • ||||||||||  AL001 / Alector
    Journal:  Vacuum-Level Shift at Al/LiF/Alq Interfaces: A First-Principles Study. (Pubmed Central) -  Aug 29, 2019   
    Dipole moment of Alq and interfacial charge rearrangement (Pauli push-back effect) are the main reasons for Δ at Al(001)-Alq and Al(001)-LiF interfaces, respectively. For a stacked Al(001)-LiF-Alq layer configuration, theory suggests a more complicated picture, which takes charge rearrangement between LiF and Alq layers into account, than a simple sum rule of dipole contributions from the two layers.
  • ||||||||||  latozinemab (GSK4527223) / GSK
    Trial completion date, Trial primary completion date:  A First in Human Study in Healthy Volunteers and in Participants With Frontotemporal Dementia With Granulin (GRN) Mutation (clinicaltrials.gov) -  Apr 19, 2019   
    P1,  N=60, Recruiting, 
    For a stacked Al(001)-LiF-Alq layer configuration, theory suggests a more complicated picture, which takes charge rearrangement between LiF and Alq layers into account, than a simple sum rule of dipole contributions from the two layers. Trial completion date: Sep 2020 --> Dec 2019 | Trial primary completion date: Mar 2020 --> Dec 2019
  • ||||||||||  AL001 / Alector, deuterated retinol (ALK-001) / Alkeus
    Journal:  Vitamin A in Stargardt disease-an evidence-based update. (Pubmed Central) -  Apr 11, 2019   
    Currently, recommendations to avoid vitamin A dietary supplementation rely mainly on a theoretical background. Animal studies on vitamin A substitute as a possible therapeutic approach in preventing or slowing vision loss in STGD1 seems promising but further clinical trials are needed to verify the results.