Alector Presents New Data from Multiple Pipeline Programs at 2021 CTAD Conference
“Since our formation, Alector has established a deep pipeline of therapeutic immuno-neurology candidates, each of which aims to harness the body’s innate immune system to slow the progression of neurodegenerative diseases. The presentations at this year’s CTAD conference highlight the diverse genetically validated targets we have in our portfolio and the progress being achieved across our pipeline,” said
Alector management will host a conference call to review and discuss data presented this week for four of its pipeline candidates at the CTAD conference and at the
AL003: Phase 1 Data in
AL003 is a humanized monoclonal antibody that targets Siglec3 (sialic acid binding Ig-like lectin 3), or CD33, a transmembrane receptor expressed by microglia cells in the brain. The Phase 1 INTERCEPT (NCT03822208) study is a randomized, placebo-controlled trial evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of single and multiple doses of AL003 in healthy volunteers and patients with mild-to-moderate Alzheimer’s disease. In this first-in-human study, AL003 showed a favorable safety and pharmacokinetic profile for once-monthly intravenous dosing. AL003 demonstrated target engagement of CD33 in both blood and central nervous system (CNS) compartments at well tolerated doses.
AL003 is being developed in collaboration with Abbvie. A randomized, controlled Phase 2 trial evaluating AL003 for the treatment of early Alzheimer’s disease is being planned for the second half of 2022.
AL101: Interim Results from a First-in-Human Study
AL101 is a human monoclonal antibody that blocks the sortilin receptor to increase progranulin, a regulator of immune activity in the brain with genetic links to multiple neurodegenerative disorders. The Phase 1 study (NCT04111666) of AL101 enrolled a total of 55 healthy volunteers in six cohorts to test the safety, tolerability, PK, PD and bioavailability of single doses of intravenously or subcutaneously administered AL101.
Study participants were randomized on a 3:8 basis to receive placebo or a single dose of AL101. The majority of the participants received a single IV infusion of AL101 in doses ranging from 6mg/kg to 60mg/kg. Another cohort received 600 mg of AL101 by subcutaneous injection. AL101 was found to be generally safe and well tolerated. The majority of on-study adverse events (AEs) were considered mild to moderate in severity, with the most frequent AEs being headache, anemia and procedural pain. Three serious adverse events were reported, but two were considered unrelated to treatment; the third was indicative of an infusion reaction. AL101 exposure increased in a dose-proportional manner after single ascending intravenous doses. The study also established that AL101 was effectively distributed into the central nervous system, as evidenced by cerebrospinal fluid concentrations of AL101. Further, study results show proof of mechanism for AL101; increases in progranulin levels were observed in the periphery and the brain persisting for one month. Alector is continuing to enroll additional cohorts to test further dosages of AL101 administered intravenously and subcutaneously.
AL101 is being developed under Alector’s collaboration with GlaxoSmithKline (GSK), and the Phase 1 study is ongoing. AL101 is the second of Alector’s progranulin-elevating therapeutic agents and is designed for less frequent dosing.
Data for AL003 and AL101, as well as a trial design poster for the Phase 3 INFRONT-3 clinical trial of AL001, are being presented at CTAD in poster presentations. The posters are available on the CTAD conference website and will be made available on the Investors section of the Alector website
- A Phase 1 Study of AL003 in
Healthy Volunteers and Participants with Alzheimer’s Disease (P45) - A First-in-human Study of the Anti-Sortilin Antibody AL101 (P46)
- Design of INFRONT-3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AL001 IN FTD-GRN (P71)
About AL003
AL003 targets CD33, or sialic acid binding Ig-like lectin 3 (Siglec-3), a known a genetic risk factor for Alzheimer’s disease. Siglec-3 is an inhibitory receptor expressed primarily on cells of myeloid lineage including microglia, which constitute the brain’s immune system. Mutations or overexpression of CD33 are understood to suppress healthy microglial activity and enable the build-up of toxic proteins, such as beta amyloid. AL003 is a monoclonal antibody that works by decreasing the expression of Siglec-3 to increase the activity of microglia. By inhibiting Siglec-3/CD33 expression, AL003 is intended to reverse inhibition of immune cell activity and restore homeostasis. AL003 is being developed by Alector in collaboration with AbbVie.
About AL101
AL101 is a human monoclonal antibody designed to increase progranulin, 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, and increased progranulin levels have been demonstrated to be protective for these diseases in animal models.
AL101 received orphan drug designation from the
About Alzheimer’s Disease
Alzheimer’s disease is a degenerative brain disease and the most common form of dementia. It is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability of patients to care for themselves. In most people with Alzheimer’s disease, symptoms first appear in their mid-60s. The Alzheimer’s Association estimates that as of 2020, there are 5.8 million Americans aged 65 and older living with Alzheimer’s disease, and projects that number will rise to nearly 14 million by 2050.
About Alector
Alector is a clinical-stage biotechnology company pioneering immuno-neurology, a novel therapeutic approach for the treatment of neurodegenerative diseases.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from current expectations and beliefs, including but not limited to risks and uncertainties related to market conditions, Alector and its business as set forth in our Quarterly Report on Form 10-Q, as filed on
Alector Contacts
VP, Communications and Investor Relations
650-808-7016
michelle.corral@alector.com
1AB (media)
973-271-6085
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212.600.1902
alector@argotpartners.com
Source: Alector, Inc.