AL101 is being developed to elevate progranulin (PGRN) levels with dosing regimens to be optimized for larger indications such as Alzheimer’s disease
Study results in healthy volunteers demonstrated that AL101 increased the level of PGRN, a key regulator of immune activity and lysosomal function in the brain
SOUTH SAN FRANCISCO, Calif., Nov. 29, 2022 (GLOBE NEWSWIRE) -- Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology and innate immuno-oncology, reported safety and biomarker data from a first-in-human Phase 1 healthy volunteer study of AL101, a human monoclonal antibody that blocks the sortilin receptor to increase progranulin levels. 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), under Alector’s collaboration with GSK.
In a randomized, double-blind, placebo-controlled Phase 1 study in 88 heathy volunteers who received either single or multiple doses of AL101 administered intravenously (IV) or subcutaneously (SC), AL101 was generally well tolerated and elevated PGRN levels in the cerebrospinal fluid (CSF). The study results that will be presented today from the multiple-dose (MD) cohorts demonstrated that the product candidate’s pharmacokinetic (PK) and pharmacodynamic (PD) profile supports development in multiple dosing schedules for chronic neurodegenerative conditions, such as AD and PD.
“Phase 1 study results demonstrated that AL101 elevated progranulin levels, and these results pave the way for exploring multiple indications and dosing schedules for AL101,” said Gary Romano, M.D., Ph.D., Chief Medical Officer of Alector. “Human genetics have shown that even moderately reduced progranulin expression may lead to an increased risk of developing neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. We are excited to have the opportunity to test the hypothesis that increasing progranulin in the brain of patients suffering from these diseases may counteract disease pathology.”
New Dosing Data from Phase 1 Study of AL101
The data that will be presented at CTAD 2022 from the multiple-dose (MD) cohorts of the Phase 1 study build upon previous data reported at CTAD 2021 from the single-dose (SD) cohorts, which demonstrated that AL101 was well tolerated and increased PGRN levels in plasma and CSF in a dose-dependent manner. In the two MD cohorts, 27 healthy volunteers received either AL101 30 mg/kg IV every four weeks (q4w) for a total of four doses [n=11] or AL101 300 mg SC every two weeks (q2w) for a total of seven doses [n=13]. Three volunteers received MD IV placebo. Key highlights from the study include the following:
AL101 was found to be generally well tolerated following MD IV (q4w) and SC (q2w) administrations.
Consistent with previously presented data following single doses, AL101 was measurable in the CSF following multiple IV and SC doses.
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 and approximately 80% (1.8-fold) above baseline in the CSF.
The PK and PD profile of AL101 following single and multiple IV doses support future development in chronic neurodegenerative conditions such as AD and PD.
Additional details will be presented during the poster presentation at CTAD 2022 and can be found in the published poster and abstract. The poster is available on the CTAD 2022 digital platform, www.ctad-alzheimer.com. The abstract will be available on the digital platform on December 2, 2022, at 5pm Pacific Standard Time (PST).
Poster Presentation Details
Poster Number: P040
Title: Repeat IV and SC Dosing of the Anti-Sortilin Antibody AL101
Date & Time: Tuesday, November 29 at 4pm PST to Wednesday, November 30 at 6pm PST
Location: Onsite at CTAD 2022
AL101 is a human monoclonal antibody designed to elevate the level of progranulin1, a regulator of immune activity in the brain with genetic links to multiple neurodegenerative disorders. Mutations that moderately reduce the expression levels of progranulin have been shown to increase the risk of developing Alzheimer’s disease and Parkinson’s disease. Increased progranulin levels have been demonstrated to be protective for these diseases in animal models.
AL101 received orphan drug designation from the U.S. Food and Drug Administration for the treatment of frontotemporal dementia in July 2019. In July 2021, Alector and GSK announced a global collaboration to co-develop and co-commercialize two progranulin-elevating candidates, latozinemab (AL001) and AL101, for a range of neurodegenerative diseases, including frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer’s disease, and Parkinson’s disease.
Alector is a clinical-stage biotechnology company pioneering immuno-neurology, a novel therapeutic approach for the treatment of neurodegenerative diseases, and innate immuno-oncology. Immuno-neurology targets immune dysfunction as a root cause of multiple pathologies that are drivers of degenerative brain disorders. Alector has discovered and is developing a broad portfolio of innate immune system programs, designed to functionally repair genetic mutations that cause dysfunction of the brain’s immune system and enable rejuvenated immune cells to counteract emerging brain pathologies. Alector’s immuno-neurology product candidates are supported by biomarkers and target genetically defined patient populations in frontotemporal dementia and Alzheimer’s disease. This scientific approach is also the basis for the company’s innate immuno-oncology programs. Alector is headquartered in South San Francisco, California. For additional information, please visit www.alector.com.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this press release include, but are not limited to, statements regarding our business plans, business strategy, product candidates, planned preclinical studies, clinical trials, expected milestones, expectations of our collaborations, and financial and cash guidance. Such statements are subject to numerous risks and uncertainties, including but not limited to risks and uncertainties as set forth in Alector’s Quarterly Report on Form 10-Q, as filed on November 8, 2022, with the Securities and Exchange Commission (“SEC”), as well as the other documents Alector files from time to time with the SEC. These documents contain and identify important factors that could cause the actual results for Alector to differ materially from those contained in Alector’s forward-looking statements. Any forward-looking statements contained in this press release speak only as of the date hereof, and Alector specifically disclaims any obligation to update any forward-looking statement, except as required by law.
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Laura Perry/Carrie McKim
1 Ward, M., Yeh, F., Park, L., et al., 2022, November. Repeat IV and SC Dosing of the Anti-Sortilin Antibody AL101. 15th Clinical Trials on Alzheimer’s Disease (CTAD), San Francisco.