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AL 002

Drug Profile

AL 002

Alternative Names: AL 002a; AL002

Latest Information Update: 31 Oct 2019

At a glance

  • Originator AbbVie; Alector
  • Class Antibodies; Antidementias; Immunotherapies; Neuroprotectants
  • Mechanism of Action TREM2 protein-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

  • Phase I Alzheimer's disease
  • Preclinical Neurodegenerative disorders

Most Recent Events

  • 14 Jul 2019 Pharmacodynamics data from preclinical trials in Alzheimer’s disease presented at the Alzheimer's Association International Conference 2019 (AAIC-2019)
  • 28 Mar 2019 Alector has patents pending for TREM2 program in USA
  • 22 Aug 2018 Alector plans a phase I trial for Alzheimer disease (In volunteers) in Australia in November 2018 (IV, Infusion) (NCT03635047)

Development Overview

Introduction

AL 002 is an antibody targeting TREM2 (Triggering Receptor Expressed on Myeloid Cells 2), expressed on microglia, being jointly developed by Alector and AbbVie, for the treatment of Alzheimer's disease and other neurodegenerative disorders. Early-stage clinical and preclinical development are underway in Australia and the US.

AL 002 has emerged from a research programme of Alector in collaboration with AbbVie on antibody therapeutics [see Adisinsight drug profile 800050570].

Company Agreements

In October 2017, AbbVie entered into a global research and development 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. Alector will conduct exploratory research, drug discovery and development for lead programs up to the conclusion of the proof of concept 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 equally. Alector will receive a $US205 million upfront payment and a potential, future equity investment of up to $US20 million. [1] [2]

Key Development Milestones

In November 2018, Alector initiated the phase I INVOKE trial evaluating safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of single and multiple doses of AL 002 (NCT03635047; AL002-1). The randomised trial intends to enrol approximately 52 healthy volunteers and patients with mild-to-moderate Alzheimer's disease in Australia [3] [4] .

In July 2019, Alector presented preclinical data of AL 002 at the Alzheimer's Association International Conference 2019 (AAIC-2019) [5] [6] [7] .

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 [8] .

Patent Information

Alector owned 3 patent families directed to the TREM2 program, which includes 4 pending US non-provisional patent applications, and multiple pending foreign patent applications all covering the compositions and uses of our TREM2 program product candidates. The patent families are expected to expire in 2035, 2036, and 2038, respectively, in all cases excluding any patent term adjustments and any patent term extensions [9] .

Drug Properties & Chemical Synopsis

  • Route of administration IV
  • Formulation unspecified
  • Class Antibodies, Antidementias, Immunotherapies, Neuroprotectants
  • Target TREM2 protein
  • Mechanism of Action TREM2 protein-inhibitors
  • WHO ATC code

    N06D-X (Other anti-dementia drugs)

    N07X (Other Nervous System Drugs)

  • EPhMRA code

    N7D (Anti-Alzheimer Products)

    N7X (All other CNS drugs)

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Alzheimer's disease - - Phase I Australia IV / unspecified Alector 15 Nov 2018
Alzheimer's disease - - Preclinical USA IV / unspecified AbbVie, Alector 25 Jul 2018
Neurodegenerative disorders - - Preclinical USA IV / unspecified AbbVie, Alector 25 Jul 2018

Commercial Information

Involved Organisations

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

Scientific Summary

Adverse Events

Intravenously administered AL 002 was safe and generally well tolerated in cynomolgus monkey toxicology studies, up to 250 mg/kg weekly dose for 4 weeks. No adverse findings were observed. The no observed adverse effect level (NOAEL) was 250 mg/kg [6] .

Pharmacodynamics

Summary

In preclinical study, administration of AL 002 activated microglia and increased clustering of microglia around amyloid plaques in 5xFAD mice models. Also a reduced amyloid deposition and improved cognition was reported with AL 002 in mice model [7] .

After multiple weekly dosing in cynomolgus monkeys, systemic exposure of intravenously administered AL 002 increased slightly less than dose proportionally with increasing doses. Some accumulation of AL 002 was observed. The ratio of serum and CSF levels of AL 002 appeared consistent across the three doses tested. A dose dependent effect on pharmacodynamic biomarkers in both serum and CSF was observed [6] .

In preclinical study the peripheral injection of antibodies triggered TREM2 signaling microglial proliferation and activation in mouse brains. These data suggested that the antibodies efficiently cross the blood-brain barrier and that TREM2 signal induction was sufficient to shift the microglia phenotype. In 5xFAD mice, chronic treatment with a TREM2 agonist caused increased expression of synaptic and myelin genes [5] .

Future Events

Expected Date Event Type Description Updated
31 Dec 2018 Trial Update Alector plans a clinical trial for Alzheimer’s disease (Monotherapy, Combination therapy) in 2018 [10] 30 Jul 2018
01 Nov 2018 Trial Update Alector plans a phase I trial for Alzheimer disease (In volunteers) in Australia in November 2018 (IV, Infusion) (NCT03635047) (700298885) 02 Jan 2019

Development History

Event Date Update Type Comment
14 Jul 2019 Scientific Update Pharmacodynamics data from preclinical trials in Alzheimer’s disease presented at the Alzheimer's Association International Conference 2019 (AAIC-2019) [5] Updated 31 Oct 2019
14 Jul 2019 Scientific Update Pharmacodynamics and safety data from preclinical trials in Alzheimer’s disease presented at the Alzheimer's Association International Conference 2019 (AAIC-2019) [6] Updated 24 Oct 2019
14 Jul 2019 Scientific Update Pharmacodynamics data from preclinical trials in Alzheimer’s disease presented at the Alzheimer's Association International Conference 2019 (AAIC-2019) [7] Updated 22 Oct 2019
28 Mar 2019 Patent Information Alector has patents pending for TREM2 program in USA [9] Updated 04 Apr 2019
15 Nov 2018 Phase Change - I Phase-I clinical trials in Alzheimer's disease in Australia (IV) [3] Updated 02 Jan 2019
22 Aug 2018 Trial Update Alector plans a phase I trial for Alzheimer disease (In volunteers) in Australia in November 2018 (IV, Infusion) (NCT03635047) Updated 02 Jan 2019
30 Jul 2018 Trial Update Alector plans a clinical trial for Alzheimer’s disease (Monotherapy, Combination therapy) in 2018 [10] Updated 30 Jul 2018
25 Jul 2018 Phase Change - Preclinical Preclinical trials in Alzheimer's disease in USA (IV) [8] Updated 30 Jul 2018
25 Jul 2018 Phase Change - Preclinical Preclinical trials in Neurodegenerative disorders in USA (IV) [8] 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 (IV) [1] Updated 30 Jul 2018
24 Oct 2017 Phase Change Early research in Neurodegenerative disorders in USA (IV) [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 Initiates Phase 1 Trial of AL002 for the Treatment of Patients with Alzheimer's Disease.

    Media Release
  4. A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Single and Multiple Doses of AL002 in Healthy Participants and in Participants With Mild to Moderate Alzheimer's Disease

    ctiprofile
  5. Schwabe T, Tassi I, Rhinn H, Ibrahim A, Kong P, Salazar S, et al. Development of TREM2 Agonistic Antibodies to Treat Alzheimer?s Disease. AAIC-2019 2019; abstr. 32469.

    Available from: URL: https://eventpilotadmin.com/web/page.php?page=IntHtml&project=AAIC19&id=32469
  6. Long H, Tu G, Schwabe T, Rhinn H, King R, Rosenthal A. Preclinical Development of TREM2 Agonist Antibody (AL002) in Cynomolgus Monkeys. AAIC-2019 2019; abstr. 32845.

    Available from: URL: https://eventpilotadmin.com/web/page.php?page=IntHtml&project=AAIC19&id=32845
  7. Price BR, Sudduth TL, Weekman EM, Woolums A, Hawthorne D, Rosenthal A, et al. Therapeutic Targeting of TREM2 By an Activating Antibody Ameliorates Amyloid-Beta Deposition and Improves Cognition in the 5xFAD Model of Alzheimer?s Disease. AAIC-2019 2019; abstr. 31373.

    Available from: URL: https://eventpilotadmin.com/web/page.php?page=IntHtml&project=AAIC19&id=31373
  8. Alector Announces $133 Million in Series E Financing to Advance Broad Portfolio of Immuno-Neurology and Immuno-Oncology Programs.

    Media Release
  9. 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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