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AL 003

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Drug Profile

AL 003

Alternative Names: AL-003

Latest Information Update: 21 Oct 2022

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At a glance

  • Originator AbbVie; Alector
  • Class Antidementias; Monoclonal antibodies
  • Mechanism of Action CD33 antigen inhibitors
  • Orphan Drug Status

    Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.

    No
  • New Molecular Entity Yes

Highest Development Phases

  • Discontinued Alzheimer's disease

Most Recent Events

  • 30 Jun 2022 Abbvie terminates the CD33 collaboration program with Alector based on the results of phase I trial
  • 30 Jun 2022 Discontinued - Phase-I for Alzheimer's disease in Australia (IV)
  • 30 Jun 2022 Discontinued - Phase-I for Alzheimer's disease in USA (IV)

Development Overview

Introduction

AL 003, a monoclonal antibody targeting Siglec-3 (CD33) was being developed by Alector in collaboration with AbbVie for the treatment of Alzheimer's disease. Siglec-3, is a transmembrane glycoprotein which is expressed on the surface of myeloid progenitor cells, mature monocytes and macrophages. Siglec-3 contains putative immunoreceptor tyrosine based inhibitory motifs which inhibit cellular activity. Upon activation, Siglec-3 constitutively repress monocyte-derived pro-inflammatory cytokines as well as microglia and their ability to dispose of the accumulated debris which cause Alzheimer's disease. Early clinical development was underway in the US and Australia. However in June 2022, Alector discontinued the development of AL 003 following termination of the CD33 collaboration agreement by AbbVie based on insufficient evidence for an effect on pharmacodynamic biomarkers in a phase I trial.

AL 003 emerged from a research programme of Alector in collaboration with AbbVie on antibody therapeutics [see Adisinsight drug profile 800050570].

Company Agreements

In February 2023, Alector and AbbVie amended the AbbVie agreement, which will result in Alector receiving a $US 17.8 million milestone payment for the dosing of the first patient in a long-term extension study. If AbbVie exercises its option for the TREM2 program, Alector will receive $US 250.0 million. Additionally, under the terms of the AbbVie Agreement, Alector will be eligible to earn up to an additional $US 225 million in milestone payments related to the regulatory approval for up to three indications. Following AbbVie’s option exercise for the TREM2 program, Alector may opt out of sharing in development costs and profits or and instead receive a tiered royalty on sales of products. Following AbbVie's exercise of an option for the TREM2 program, AbbVie would be responsible for certain development activities and global commercialization, taking advantage of its global clinical trial expertise and commercialization networks. In June 2022, AbbVie terminated the CD33 collaboration program after AbbVie and Alector collaboratively reviewed progress for AL 003 and concluded that further development of AL003 was not warranted. Alector will continue the development of the AL002 program (TREM2) under the AbbVie Agreement but will not be eligible for any future milestones related to the CD33 collaboration program from AbbVie. In October 2017, AbbVie entered into a global research and development agreement (AbbVie agreement) with Alector, to develop and commercialise immune therapies for the treatment of Alzheimer's disease and other neurodegenerative disorders. Under the terms of the agreement, AbbVie and Alector have agreed to research a portfolio of antibody targets and AbbVie has an option to global development and commercial rights to two targets which include a triggering receptor expressed on myeloid cells 2 (TREM2) and Siglce-3 receptor (CD33). Alector will conduct exploratory research, drug discovery and development for lead programs up to the conclusion of the proof of concept studies including the design and execution of phase I and phase II studies. Upon exercising the option, AbbVie will lead development and commercialisation activities. Alector and AbbVie will co-fund development and commercialisation and will share global profits and losses equally after marketing approval. Alector will receive a $US205 million upfront payment and a potential, future equity investment of up to $US20 million if AbbVie exercises its option for either program (or both programs), Alector is eligible for additional option exercise and milestone payments totaling up to $US986M. Additionally, under the terms of the AbbVie Agreement, Alector is eligible to earn up to an additional $242.8 million in milestone payments related to the initiation of certain clinical studies and regulatory approval for up to three indications. [1] [2] [3] [4]

Key Development Milestones

Alector discontinued the development of AL 003 in June 2022 following termination of the CD33 collaboration agreement by AbbVie. AbbVie terminated the CD33 collaboration program after AbbVie and Alector collaboratively reviewed AL 003 progress and concluded to discontinue its further development based on insufficient evidence for an effect on pharmacodynamic biomarkers in a phase I trial [4] .

In May 2021, Alector completed a first in human (FIH) phase I trial of AL 003 in healthy volunteers and in patients with mild to moderate Alzheimer's disease (AL003-1; NCT03822208). The trial is designed to evaluate the safety, immunogenicity, tolerability, pharmacokinetics and pharmacodynamics of AL 003. The randomised, double-blind, placebo-controlled, dose escalation trial was initiated in March 2019 and enrolled 54 participants in the US and Australia. Peripheral PK and PD in participants, were dose-dependent. In April 2022, data were presented at the 74th Annual Meeting of the American Academy of Neurology 2022 (AAN-2021) [5] [6] .

Financing information

In July 2018, Alector secured $US133 million in Series E financing round. The company has previously raised $US282 million. The company expect to utilize the proceeding from the financing to advance Alector’s clinical programs and expand the company’s discovery platform [7] .

Patent Information

As at April 2022, Alector owns six patent families directed to SIGLEC 3 programme, which include three issued US patents, covering the compositions and uses of SIGLEC 3 programme candidates. The first two patent families are expected to expire in 2036, the third patent family is expected to expire in 2038, the fourth patent family is expected to expire in 2039, the fifth patent family is expected to expire in 2040, and the sixth patent family, assuming that the applications are timely filed, is expected to expire in 2042 [8] [9] [10] .

Drug Properties & Chemical Synopsis

  • Route of administration IV
  • Formulation Infusion
  • Class Antidementias, Monoclonal antibodies
  • Target CD33 antigen
  • Mechanism of Action CD33 antigen inhibitors
  • WHO ATC code

    N06D-X (Other anti-dementia drugs)

  • EPhMRA code

    N7D (Anti-Alzheimer Products)

Biomarkers Sourced From Trials

Indication Biomarker Function Biomarker Name Number of Trials

Alzheimer's disease

Outcome Measure

Granulocyte-macrophage colony-stimulating factor (GM-CSF)

1

Biomarker

Drug Name Biomarker Name Biomarker Function
AL 003 Granulocyte-macrophage colony-stimulating factor (GM-CSF) Outcome Measure
For more detail, check out BiomarkerBase: the leading source of information about biomarkers used in drug development and diagnostic tests, tracking a comprehensive list of biomarker uses worldwide by over 800 companies

Trial Landscape

Indication Phase 0 Phase I Phase II Phase III Phase IV
Alzheimer's disease - 1 - - -

Development Status

Summary Table

Download Data (CSV)
Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Alzheimer's disease - - Discontinued (I) Australia IV / Infusion Alector 30 Jun 2022
Alzheimer's disease - - Discontinued (I) USA IV / Infusion AbbVie, Alector 30 Jun 2022

Commercial Information

Involved Organisations

Organisation Involvement Countries
Alector Originator USA
AbbVie Originator USA
Alector Owner USA
AbbVie Owner USA

Scientific Summary

Adverse Events

Treatment with IV AL 003 was safe and generally well tolerated, in healthy volunteers and in patients (n=54) with mild to moderate Alzheimer's disease, in a phase I trial. The most frequently reported adverse events were headache (20.7%), post-lumbar puncture syndrome (i.e., headache after lumbar puncture; 17.2%), nausea (13.8%), upper respiratory tract infection (13.8%), and puncture site pain (10.3%). Dose levels up to 15 mg/kg were well tolerated in HVs with immune-related adverse events at higher dose levels [5] [6] .

Future Events

Expected Date Event Type Description Updated
31 Mar 2019 Trial Update Alector plans a phase I trial for Alzheimer’s disease in March 2019 (NCT03822208) 03 May 2019
31 Dec 2018 Trial Update Alector plans a clinical trial for Alzheimer’s disease (Monotherapy, Combination therapy) in 2018 [11] 01 Feb 2019

Development History

Event Date Update Type Comment
30 Jun 2022 Licensing Status Abbvie terminates the CD33 collaboration program with Alector based on the results of phase I trial [4] Updated 21 Oct 2022
30 Jun 2022 Phase Change - Discontinued(I) Discontinued - Phase-I for Alzheimer's disease in Australia (IV) [4] Updated 21 Oct 2022
30 Jun 2022 Phase Change - Discontinued(I) Discontinued - Phase-I for Alzheimer's disease in USA (IV) [4] Updated 21 Oct 2022
04 Jun 2022 Active Status Review Phase-I development is ongoing in USA and Australia (IV, Infusion) Updated 04 Jun 2022
21 Apr 2022 Patent Information Alector has patent pending for compositions and uses of SIGLEC 3 programme candidates in USA [8] Updated 22 Apr 2022
21 Apr 2022 Patent Information Alector has patent protection for compositions and uses of SIGLEC 3 programme candidates in USA [8] Updated 22 Apr 2022
02 Apr 2022 Scientific Update Adverse events data from a phase I trial in Alzheimer's disease presented at the 74th Annual Meeting of the American Academy of Neurology 2022 (AAN-2022) [5] Updated 04 Jun 2022
17 Sep 2021 Biomarker Update Biomarkers information updated Updated 02 Oct 2021
06 May 2021 Trial Update Alector completes a phase I trial in Alzheimer's disease in the US and Australia (IV) (NCT03822208) Updated 27 Sep 2021
31 Dec 2020 Patent Information Alector has patent protection for SIGLEC 3 program in USA [9] Updated 18 Jun 2021
29 Mar 2019 Phase Change - I Phase-I clinical trials in Alzheimer's disease in USA (IV) (NCT03822208) Updated 27 Sep 2021
29 Mar 2019 Phase Change - I Phase-I clinical trials in Alzheimer's disease in Australia (IV) (NCT03822208) Updated 03 May 2019
28 Mar 2019 Patent Information Alector has patents pending for SIGLEC 3 program in USA [10] Updated 04 Apr 2019
31 Jan 2019 Trial Update Alector plans a phase I trial for Alzheimer’s disease in March 2019 (NCT03822208) Updated 03 May 2019
30 Jul 2018 Trial Update Alector plans a clinical trial for Alzheimer’s disease (Monotherapy, Combination therapy) in 2018 [11] Updated 01 Feb 2019
25 Jul 2018 Phase Change - Preclinical Preclinical trials in Alzheimer's disease in USA (Parenteral) [7] Updated 30 Jul 2018
24 Oct 2017 Licensing Status Alector and AbbVie agree to co-promote and co-develop antibody therapeutics worldwide for Alzheimer's disease and Neurodegenerative disorders [1] Updated 30 Jul 2018
24 Oct 2017 Phase Change Early research in Alzheimer's disease in USA (Parenteral) [1] Updated 30 Jul 2018

References

  1. Alector and AbbVie Announce Collaboration to Advance a Novel Class of Immune Therapies for Patients with Alzheimer's Disease.

    Media Release

  2. Alector Snags $133M to Activate Immune Cells Against Neurodegeneration. Internet-Doc 2018;.

    Available from: URL: https://www.xconomy.com/san-francisco/2018/07/25/alector-snags-133m-to-activate-immune-cells-against-neurodegeneration/2/

  3. Alector Announces Publication of Preclinical and Phase 1 Data Validating Potential of AL002, a TREM2 Activating Antibody for the Treatment of Alzheimers Disease, in The Journal of Experimental Medicine.

    Media Release

  4. Alector, Inc Form Q Sec Filing. Internet-Doc 2022;.

    Available from: URL: https://investors.alector.com/static-files/813eba5c-745b-4100-be5f-97873a288915

  5. Maslyar D, Paul R, Long H, Rhinn H, Tassi I, Morrison G, et al. A Phase 1 Study of AL003 in Healthy Volunteers and Participants with Alzheimer?s disease. AAN-2022 2022; abstr. P5.002.

    Available from: URL: https://index.mirasmart.com/aan2022/PDFfiles/AAN2022-003582.html

  6. A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Single and Multiple Doses of AL003 in Healthy Participants and in Participants With Mild to Moderate Alzheimer's Disease.

    ctiprofile

  7. Alector Announces $133 Million in Series E Financing to Advance Broad Portfolio of Immuno-Neurology and Immuno-Oncology Programs.

    Media Release

  8. Alector_SEC Form 10-K_Apr 2022. Internet-Doc 2022;.

    Available from: URL: https://www.sec.gov/ix?doc=/Archives/edgar/data/1653087/000095017022001979/alec-20211231.htm

  9. Alector SEC filing, Form 10-K. Internet-Doc 2021;.

    Available from: URL: https://www.sec.gov/Archives/edgar/data/1653087/000156459021008860/alec-10k_20201231.htm

  11. Alector Closes $133 Million to Expand Alzheimer?s Programs. Internet-Doc 2018;.

    Available from: URL: https://www.biospace.com/article/alector-closes-133-million-to-expand-alzheimer-s-programs/
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