Therapeutics

ALZ-101

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Overview

Name: ALZ-101
Therapy Type: Immunotherapy (active) (timeline)
Target Type: Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 1)
Company: Alzinova AB

Background

This candidate vaccine is designed to provoke an immune response specific to soluble oligomeric Aβ assemblies, but not to monomeric or fibrillar Aβ. A proprietary protein-engineering technology uses disulfide bonds to cross-link Aβ peptides into a conformation that assembles into stable, soluble oligomers or protofibrils (Sandberg et al., 2010; Dubnovitsky et al., 2013). These assemblies are formulated into the ALZ-101 vaccine.

In preclinical work, mice immunized with ALZ-101 were the source of a monoclonal antibody that bound to oligomeric Aβ, but not plaques or non-aggregated peptides (Sandberg et al., 2022). The antibody was able to deplete toxic Aβ from human AD brain extracts.

Findings

In September 2021, Alzinova began a Phase 1b study in Finland to evaluate tolerability, safety and immunological response to the vaccine. The blinded study has enrolled 27 patients with CSF biomarker-confirmed early AD to receive four intramuscular injections of 125 or 250 μg ALZ-101 or placebo over 16 weeks. Primary endpoints are adverse events, especially related to injection, amyloid-related imaging abnormalities, and cognitive or functional worsening in the year after vaccination. Secondary outcomes pertain to Aβ-specific antibody responses. Exploratory endpoints are blood and CSF AD biomarkers. In September 2023, the company added an open-label extension comprising two additional doses over 16 weeks. The trial will run through December 2023.

For trial details, see clinicaltrials.gov.

Last Updated: 06 Oct 2023

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References

Paper Citations

  1. Sandberg A, Luheshi LM, Söllvander S, Pereira de Barros T, Macao B, Knowles TP, Biverstål H, Lendel C, Ekholm-Petterson F, Dubnovitsky A, Lannfelt L, Dobson CM, Härd T. Stabilization of neurotoxic Alzheimer amyloid-beta oligomers by protein engineering. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15595-600. PubMed.
  2. Dubnovitsky A, Sandberg A, Rahman MM, Benilova I, Lendel C, Härd T. Amyloid-β protofibrils: size, morphology and synaptotoxicity of an engineered mimic. PLoS One. 2013;8(7):e66101. PubMed.
  3. Sandberg A, Berenjeno-Correa E, Rodriguez RC, Axenhus M, Weiss SS, Batenburg K, Hoozemans JJ, Tjernberg LO, Scheper W. Aβ42 oligomer-specific antibody ALZ-201 reduces the neurotoxicity of Alzheimer's disease brain extracts. Alzheimers Res Ther. 2022 Dec 29;14(1):196. PubMed.

External Citations

  1. clinicaltrials.gov

Further Reading

Papers

  1. Dubnovitsky A, Sandberg A, Rahman MM, Benilova I, Lendel C, Härd T. Amyloid-β protofibrils: size, morphology and synaptotoxicity of an engineered mimic. PLoS One. 2013;8(7):e66101. PubMed.
  2. Dubnovitsky A, Sandberg A, Rahman MM, Benilova I, Lendel C, Härd T. Amyloid-β protofibrils: size, morphology and synaptotoxicity of an engineered mimic. PLoS One. 2013;8(7):e66101. PubMed.