nivisnebart (GSK4527226) / Alector, GSK - LARVOL DELTA

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

Alector Presents Results from First-in-Human Phase 1 Study of AL101 for the Treatment of Neurodegenerative Diseases (GlobeNewswire) - P1 | N=88 | NCT04111666 | Sponsor: Alector Inc. | “Alector, Inc…reported safety and biomarker data from a first-in-human Phase 1 healthy volunteer study of AL101…The data will be presented today during a poster session at the 15th Clinical Trials on Alzheimer's Disease (CTAD) conference held in San Francisco from November 29–December 2, 2022. AL101 is being developed for the potential treatment of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD)…AL101 was found to be generally well tolerated following MD IV (q4w) and SC (q2w) administrations….MD administration of AL101 increased plasma and CSF PGRN levels, with a higher elevation observed in the AL101 30 mg/kg MD IV group than in the AL101 300 mg MD SC group. Multiple IV doses of AL101 at 30 mg/kg increased and maintained the levels of PGRN at approximately 160% to 200% (2.6- to 3-fold) above baseline in plasma..."

Biomarker • P1 data • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

A Phase 1 First in Human Study to Assess Safety and Tolerability of AL101 (clinicaltrials.gov) - P1 | N=88 | Completed | Sponsor: Alector Inc. | Active, not recruiting ➔ Completed | Trial completion date: Sep 2022 ➔ Jun 2022

Trial completion • Trial completion date

Alector Reports Second Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - “Progranulin Assets (Latozinemab, AL101): The company expects to report data at a medical conference later this year from the Phase 1 trial of AL101 in healthy volunteers. AL101 is being developed to elevate progranulin levels in a manner similar to latozinemab (AL001) with plans to investigate AL101 for the treatment of AD and Parkinson’s disease….Total research and development expenses for the quarter ended June 30, 2022, were $54.5 million, compared to $47.8 million for the quarter ended June 30, 2021. The increase in R&D expenses was mainly driven by increased personnel-related expenses, including stock-based compensation, as well as an increase in AL101 expenses.”

Commercial • P1 data • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

A Phase 1 First in Human Study to Assess Safety and Tolerability of AL101 (clinicaltrials.gov) - P1 | N=79 | Active, not recruiting | Sponsor: Alector Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

Alector Reports First Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - "Alector, Inc...today reported first quarter 2022 financial results and recent portfolio and business updates. As of March 31, 2022, Alector’s cash, cash equivalents, and marketable securities totaled $868.6 million....Alector completed enrollment in the ongoing Phase 1 clinical trial to test multiple doses of AL101 administered intravenously and subcutaneously....The company expects to report data from the Phase 1 trial in the second half of 2022."

Enrollment closed • P1 data • Alzheimer's Disease • CNS Disorders • Parkinson's Disease