Name: Semorinemab
Synonyms: RO7105705, MTAU9937A, RG6100
Therapy Type: Immunotherapy (passive) (timeline)
Target Type: Tau (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: AC Immune SA, Genentech, Hoffmann-La Roche


This is an anti-tau IgG4 antibody that grew out of a research collaboration between AC Immune and Genentech, part of the Roche Group. The collaboration focused on approaches that target extracellular, not intracellular, tau. The aim was to explore antibodies with reduced effector function in an effort to limit microglial activation leading to inflammatory responses (Lee et al., 2016). At the 2017 AD/PD conference, Genentech reported that RO7105705 binds the N-terminus of all six isoforms of human tau, both monomeric and oligomeric, regardless of phosophorylation status, and that 13 weeks of treatment with either 3, 10, or 30 mg/kg of the antibody dose-dependently reduced brain pathology while raising plasma tau levels in P301L mice. Chronic dosing was safe in mice or cynomolgus monkeys, Genentech also reported (Apr 2017 conference news). 


From June 2016 to June 2017, Genentech ran a Phase 1 study of 74 volunteers comprising both healthy controls and people with mild to moderate Alzheimer's disease. Conducted in Tennessee, this trial compared the antibody to placebo on safety, tolerability, pharmacokinetics, and preliminary activity outcomes. It combined single dose, dose-escalation, and multiple dosing, given both intravenously and subcutaneously. At the 2017 AD/PD and AAIC conferences, Genentech reported that single doses in healthy volunteers went as high as 16,800 mg, with a 15-day window observed between a given dose and the next higher dose, and that 70 percent of the subcutaneous doses were bioavailable. Results remained blinded at this point in time, but the trial had not generated serious adverse events; minor AEs related to the drug included bruising and pain at the injection site. RO7105705 plasma half-life was 32 days, and plasma and CSF concentration increased with dose (Apr 2017 conference newsAug 2017 conference news).

In October 2017, Genentech started TAURIEL, a Phase 2 study in 360 people with prodromal or probable AD ascertained by a positive amyloid PET or CSF Aβ42 finding, and mild symptoms. Participants are randomized to an 18-month course of placebo or one of three doses of RO7105705 infusion, with a 96-week open label extension option for those who completed the blinded portion of the trial. This trial uses Genentech's tau PET tracer GTP1 at baseline and to measure treatment response at week 73. Primary outcomes are change on the CDR-sum of boxes and safety; secondary measures include the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), the new Amsterdam Instrumental Activity of Daily Living questionnaire, the ADAS-cog13 and ADCS-ADL Inventory, as well as serum drug concentration and anti-drug antibodies. This trial runs at 153 locations in North America, Australia, and various European countries; primary completion is expected in 2020.

In February 2019, Roche started another Phase 2 study in 260 people with a diagnosis of probable AD confirmed by amyloid positivity via PET or CSF testing, and with moderate dementia. The study comprises a screening, double-blind treatment, optional open-label extension period, and a safety follow-up period. Primary endpoints are change from baseline to week 49 on both ADAS-Cog1 and ADCS-ADL; secondary endpoints include CDR-SB, MMSE, adverse events, serum concentation of RO7105705, and anti-drug antibodies to RO7105705. As of 20 February 2019, seven U.S. sites were listed; the trial is set to run until 2021.

For all trials with this antibody, see

Last Updated: 20 Feb 2019


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News Citations

  1. Treating Tau: Finally, Clinical Candidates Are Stepping into the Ring
  2. High-Dose Aβ and Tau Immunotherapies Complete Initial Safety Tests

Paper Citations

  1. . Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial Engagement. Cell Rep. 2016 Aug 9;16(6):1690-700. Epub 2016 Jul 28 PubMed.

External Citations


Further Reading