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 FcγReceptor (Andersson et al., 2019).
In September 2019, Lundbeck initiated a Phase 1 single-dose study of Lu AF87908. Conducted in Los Angeles, the placebo-controlled trial plans to enroll 96 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 March 2021.
For details on Lu AF87908 trials, see clinicaltrials.gov.
Last Updated: 25 Jun 2020
- 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.
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