nivisnebart (AL101) / Alector - LARVOL DELTA

PROGRESS-AD: Efficacy and Safety of GSK4527226 [AL101] in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=367 | Terminated | Sponsor: GlaxoSmithKline | Trial completion date: Nov 2026 ➔ Aug 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2026 ➔ May 2026; The study was terminated early due to meeting pre-specified efficacy futility criteria at planned interim analysis.

Trial completion date • Trial primary completion date • Trial termination • Alzheimer's Disease • CNS Disorders

Alector…said on Wednesday that GSK…had terminated their neuroscience collaboration agreement covering ​two experimental antibody drugs after both ‌the drug candidates suffered clinical setbacks (Reuters) - "The decision follows the failure of a late-stage study of latozinemab ​in a rare inherited form of ​frontotemporal dementia last year and the discontinuation of ⁠a mid-stage Alzheimer's disease trial of ​nivisnebart in April....GSK's termination notice ​relates to the companies' 2021 collaboration and license agreement for the development of monoclonal antibodies latozinemab and ​nivisnebart....The termination will take effect on January 2 next year, following ⁠a 180-day ​notice period that began ​when GSK provided written notice on July 6."

Licensing / partnership • Alzheimer's Disease • Dementia • Frontotemporal Lobar Degeneration

Alector…confirmed that the Phase 2 PROGRESS-AD trial of nivisnebart (AL101/GSK4527226) in individuals with early Alzheimer’s disease (AD) will be discontinued (GlobeNewswire) - "The decision follows a pre-specified futility analysis conducted by an IDMC, which concluded that the trial was unlikely to meet its primary endpoint of slowing disease progression at completion....The companies will work closely with study investigators to inform participants enrolled in the PROGRESS-AD trial. Full results will be shared at a future medical meeting or congress."

P2 data • Trial termination • Alzheimer's Disease

223646: GSK4527226 Open-label Extension Study in Patients with Early Alzheimer's Disease. (clinicaltrialsregister.eu) - P1/2 | N=143 | Recruiting | Sponsor: Glaxosmithkline Research & Development Limited

New P1/2 trial • Alzheimer's Disease • CNS Disorders

Biomarkers. (PubMed, Alzheimers Dement) - P2 | "Utilizing blood-based biomarkers significantly decreased the number of participants required to have unnecessary CSF or PET testing. Limitations of this study are incomplete confirmatory results for amyloid negative individuals, regional PET/CSF confirmatory test bias, and the delay between historical result and blood biomarker testing. Including blood-based biomarkers in screening can reduce participant burden, enhance access and enrollment and improve clinical trial design."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • p-tau181 • SORT1

Progranulin Programs (nivisnebart (AL101/GSK4527226) (GlobeNewswire)

P2 data • Alzheimer's Disease

Open-label Extension Study in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=297 | Recruiting | Sponsor: GlaxoSmithKline | N=226 ➔ 297 | Not yet recruiting ➔ Recruiting

Enrollment change • Enrollment open • Alzheimer's Disease • CNS Disorders

Alector to Host Virtual Research and Development Event Highlighting PGRN Franchise and Brain Carrier Programs (GlobeNewswire) - "The event will include a review of latozinemab, currently being evaluated in a pivotal Phase 3 trial for frontotemporal dementia due to a GRN gene mutation, and AL101, which is in a Phase 2 trial for early Alzheimer’s disease (AD). In addition, the company will present preclinical data on lead candidates for its ABC–enabled programs, including its brain-penetrant anti-amyloid beta antibody program for AD, and its brain-penetrant engineered GCase-enzyme replacement therapy for Parkinson’s disease. The event will also highlight progress in Alector’s ABC-enabled siRNA programs, which expand the platform’s reach across different cargos for the treatment of neurodegenerative diseases."

Clinical • Preclinical • Alzheimer's Disease • Frontotemporal Lobar Degeneration • Gaucher Disease • Lewy Body Disease • Parkinson's Disease

GSK highlights new findings on...Alzheimer’s Disease at AAIC 2025, building on leadership in immunology and inflammation (GSK Press Release) - "Posters on GSK5862611 and PROGRESS-AD focus on new therapeutic approaches to neurodegenerative diseases..Using advanced lab models made from human stem cells carrying a genetic risk variant (TDP43 G298S), the study aimed to better understand how the GSK5862611 antibody works and gather evidence to support its development as a treatment for these challenging diseases...provides insight into using blood tests to more easily detect specific biomarkers that indicate the presence of amyloid, a protein linked to Alzheimer’s."

P2 data • Preclinical • Alzheimer's Disease • CNS Disorders

Development of AL101 (GSK4527226), a progranulin-elevating monoclonal antibody, as a potential treatment for Alzheimer's disease. (PubMed, Alzheimers Res Ther) - P1 | "AL101 was shown to bind sortilin and decrease cell surface sortilin levels, leading to consistent elevations of PGRN across in vitro, preclinical, and human studies. These results support continued development of AL101 and its investigation as a potential treatment for AD and other neurodegenerative conditions where PGRN could play a role."

Journal • Alzheimer's Disease • CNS Disorders • SORT1

Recent Clinical Updates (GlobeNewswire) - "The global, randomized, double-blind, placebo-controlled PROGRESS-AD Phase 2 clinical trial of AL101/GSK4527226 in early Alzheimer’s disease (AD) is ongoing, with enrollment completed in April 2025 and trial completion expected in 2026....Alector is currently evaluating potential candidates and continues to target clinical entry for ADP037-ABC and ADP050-ABC in 2026, pending resource allocation, lead candidate selection, and the results of preclinical studies."

New trial • Trial completion date • Alzheimer's Disease • Gaucher Disease • Lewy Body Disease • Parkinson's Disease

Open-label Extension Study in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=226 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P2 trial • Alzheimer's Disease • CNS Disorders

Alector Announces Completion of Enrollment in the PROGRESS-AD Phase 2 Clinical Trial of AL101/GSK4527226 in Individuals with Early Alzheimer’s Disease (GlobeNewswire) - "Alector, Inc...announced the completion of enrollment in PROGRESS-AD, a 76-week Phase 2 clinical trial evaluating the safety and efficacy of AL101/GSK4527226 in slowing disease progression in individuals with early Alzheimer’s disease (AD)."

Enrollment closed • Alzheimer's Disease

PROGRESS-AD: Efficacy and Safety of GSK4527226 [AL101] in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=359 | Active, not recruiting | Sponsor: GlaxoSmithKline | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders

PROGRESS-AD: Efficacy and Safety of GSK4527226 [AL101] in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=282 | Recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Feb 2029 ➔ Nov 2026

Trial completion date • Alzheimer's Disease • CNS Disorders

Alector Reports on Recent Progress and Outlines Strategic Priorities for 2025 (GlobeNewswire) - "Topline data from the pivotal INFRONT-3 Phase 3 clinical trial of latozinemab in FTD-GRN expected by Q4 2025; Completion of enrollment in the PROGRESS-AD Phase 2 trial of AL101/GSK4527226 for early Alzheimer’s disease anticipated in mid-2025, with approximately 75% target recruitment achieved..."

Enrollment status • P3 data: top line • Alzheimer's Disease • Dementia • Frontotemporal Lobar Degeneration

Drug Development. (PubMed, Alzheimers Dement) - P2 | "This study of the anti-sortilin antibody, GSK4527226, will comprehensively evaluate its efficacy, safety and effects on pathogenesis in early AD."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • GRN • SORT1

Alector to Present Data on Pipeline Focus Areas at the Alzheimer’s Association International Conference (AAIC) 2024 (GlobeNewswire) - "Alector, Inc...today announced presentations related to the Company’s TREM2 and progranulin programs at the upcoming Alzheimer's Association International Conference 2024 (AAIC) being held online and in Philadelphia, Pennsylvania from July 28 – August 1, 2024. Poster presentations will be available for on-demand viewing beginning on July 28 at 8:00 a.m. ET."

Clinical • P2 data • Preclinical • Alzheimer's Disease • CNS Disorders

PROGRESS-AD: a phase 2 study to evaluate efficacy and safety of GSK4527226 (AL101), an anti-sortilin monoclonal antibody, in patients with early Alzheimer's disease (AAIC 2024) - P2 | "This study of the anti-sortilin antibody, GSK4527226, will comprehensively evaluate its efficacy, safety and effects on pathogenesis in early AD."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • GRN • SORT1

Alector Reports First Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Alector and GSK plan to present a poster on the design of the AL101 Phase 2 trial at the Alzheimer's Association International Conference 2024 (AAIC) in Philadelphia from July 28 to August 1, 2024....The INVOKE-2 Phase 2 clinical trial of AL002 is fully enrolled, and data from the trial are anticipated in the fourth quarter of 2024."

Clinical protocol • Enrollment closed • P2 data • Alzheimer's Disease • CNS Disorders

PROGRESS-AD: Efficacy and Safety of GSK4527226 [AL101] in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=282 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders

Alector Announces First Patient Dosed in PROGRESS-AD Phase 2 Clinical Trial of AL101/GSK4527226 in Patients with Early Alzheimer’s Disease (Yahoo Finance) - "Alector, Inc...and GSK plc...today announced that the first patient has been dosed in PROGRESS-AD, the global Phase 2 clinical trial of AL101/GSK4527226 in patients with early Alzheimer’s disease (AD), including mild cognitive impairment and mild dementia due to AD. AL101 is an investigational human monoclonal antibody designed to block and downregulate the sortilin receptor to elevate the level of progranulin in the brain in a manner similar to investigational latozinemab but with different pharmacokinetic (PK) and pharmacodynamic (PD) properties."

Trial status • Alzheimer's Disease • CNS Disorders

PROGRESS-AD: Efficacy and Safety of GSK4527226 [AL101] in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=282 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P2 trial • Alzheimer's Disease • CNS Disorders

Repeat IV and SC Dosing of the Anti-Sortilin Antibody AL101 (AAN 2023) - "Conclusions Repeat IV or SC administration of AL101 is generally safe and well tolerated. AL101 is a potent modulator of PGRN levels in the CSF, with a PK/PD profile that supports its further development in neurodegenerative diseases."

Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Movement Disorders • Parkinson's Disease • SORT1

REPEAT IV AND SC DOSING OF THE ANTISORTILIN ANTIBODY AL101 (CTAD 2022) - "Multiple IV or SC administration of AL101 is generally safe and well tolerated in healthy volunteers. AL101 is a potent modulator of PGRN levels in the CSF, with a PK/PD profile that supports its further development in chronic neurological conditions such as Alzheimer’s and Parkinson’s disease."

Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Immunology • Movement Disorders • Parkinson's Disease • SORT1