Overview

Name: Lu AF87908
Synonyms: hC10.2
Therapy Type: Immunotherapy (passive) (timeline)
Target Type: Tau (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 1)
Company: Lundbeck

Background

Lu AF87908 is a humanized mouse IgG1 monoclonal antibody to phosphorylated tau protein. It was generated by immunization of mice with a tau peptide spanning residues 386-408 and phosphorylated at serine 396 and 404.

In preclinical work, the mouse version of this antibody, C10.2, preferentially bound hyperphosphorylated tau aggregates from brain, and reduced the ability of brain-derived tau to seed aggregation in cultured neurons and in rTg4510 tau transgenic mice (Rosenqvist et al., 2018). The antibody mediated uptake and lysosomal degradation of mouse-brain-derived pathological tau aggregates in primary microglia in culture; notably, this required effector function via the antibody's Fcγ receptor (Andersson et al., 2019). The humanized antibody bound to phosphorylated tau in postmortem brain from cases of AD and primary tauopathies, and prevented seeding of aggregation by brain extracts (Helboe et al., 2022). Intravenous administration caused a dose-dependent decrease in CSF pS396-tau in rTg4510 mice (Jacobsen et al., 2023).

Findings

In September 2019, Lundbeck initiated a Phase 1 single-dose study of Lu AF87908. Conducted at six sites in the U.S., the placebo-controlled trial plans to enroll 86 adults in three sequential cohorts: healthy, healthy Japanese and Chinese, and patients with Alzheimer’s disease. Safety and plasma antibody concentrations will be monitored for three months after infusion. The study is scheduled to run through June 2023.

For details on Lu AF87908 trials, see clinicaltrials.gov.

Last Updated: 28 Feb 2023

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References

Paper Citations

Rosenqvist N, Asuni AA, Andersson CR, Christensen S, Daechsel JA, Egebjerg J, Falsig J, Helboe L, Jul P, Kartberg F, Pedersen LØ, Sigurdsson EM, Sotty F, Skjødt K, Stavenhagen JB, Volbracht C, Pedersen JT. Highly specific and selective anti-pS396-tau antibody C10.2 targets seeding-competent tau. Alzheimers Dement (N Y). 2018;4:521-534. Epub 2018 Oct 14 PubMed.
Andersson CR, Falsig J, Stavenhagen JB, Christensen S, Kartberg F, Rosenqvist N, Finsen B, Pedersen JT. Antibody-mediated clearance of tau in primary mouse microglial cultures requires Fcγ-receptor binding and functional lysosomes. Sci Rep. 2019 Mar 15;9(1):4658. PubMed.
Helboe L, Rosenqvist N, Volbracht C, Pedersen LØ, Pedersen JT, Christensen S, Egebjerg J, Christoffersen CT, Bang-Andersen B, Beach TG, Serrano GE, Falsig J. Highly Specific and Sensitive Target Binding by the Humanized pS396-Tau Antibody hC10.2 Across a Wide Spectrum of Alzheimer's Disease and Primary Tauopathy Postmortem Brains. J Alzheimers Dis. 2022;88(1):207-228. PubMed.
Jacobsen AM, van de Merbel NC, Ditlevsen DK, Tvermosegaard K, Schalk F, Lambert W, Bundgaard C, Pedersen JT, Rosenqvist N. A Quantitative LC-MS/MS Method for Distinguishing the Tau Protein Forms Phosphorylated and Nonphosphorylated at Serine-396. J Am Soc Mass Spectrom. 2023 Mar 1;34(3):441-451. Epub 2023 Jan 31 PubMed.

Therapeutics

Lu AF87908

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