Drug name
Last update: Sep 202610E8.4/iMab
Developer(s)
Drug information
Not provided
10E8.4/iMab bispecific broadly neutralising antibody; derived from 10E8V2.0/iMab (CrossMAb format)
Not applicable (investigational; no brand name assigned)
Biotherapeutic
Bispecific broadly neutralising antibody (gp41 MPER bNAb arm plus anti-CD4 post-attachment inhibitor arm);; derived from 10E8V2.0/iMab
10E8.4/iMab is a bispecific antibody developed at the Aaron Diamond AIDS Research Center, Columbia University. One arm is 10E8.4, which binds the membrane-proximal external region (MPER) of HIV-1 gp41, a highly conserved fusion-critical epitope. The other arm is ibalizumab (iMab), a humanised anti-CD4 antibody that blocks HIV entry post-attachment. The two arms are joined in a knob-into-hole CrossMab architecture, and the molecule is engineered for extended in vivo half-life and reduced Fc-effector function to limit IgG-mediated toxicity. Linking the arms produces marked synergy: the parent construct 10E8V2.0/iMab neutralised a 118-virus tier-2 pseudovirus panel with a mean IC50 of 0.002 microgram/mL and 99% of a 200-isolate clade C panel. PK PD simulaiton https://pk10e8imab.fredhutch.org
Not approved in any jurisdiction as of September 2026. Investigational; phase 1. The first-in-human study (NCT03875209) is complete and published; a phase 1b single-dose study alone and with VRC07-523LS is under way in Tanzania (RV584, NCT05890963).
No marketing authorisation application identified. Developed under a US FDA IND held by Columbia University Irving Medical Center.
Therapeutic area(s)
- HIV
- Pre-Exposure Prophylaxis (PrEP)
- Treatment
Administration route
Intravenous, Route of administration is being determined in the clinical program, Subcutaneous
Associated long-acting platforms
Monoclonal antibodies and antibody drug conjugates
Use of drug
- Administered by a nurse
- Administered by a specialty health worker
- Other/Variable/Unknown : single dose studied to date; dosing interval not established
Dosage
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bispecific monoclonal antibody, potentially to be used alone or in combination with VRC07-523LS. It is tested for prevention (IV) as well as for treatment of HIV
Not provided
Related entries
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Additional information
Developer(s)
Columbia University
Drug structure
Scale-up and manufacturing prospects
Not reported. Clinical supply was manufactured to GMP and shipped to sites from a designated GMP storage facility. Bispecific CrossMab formats add chain-pairing and purification complexity relative to conventional IgG.
Not reported for this product. Standard mAb train assumed, with additional analytics for correct heavy-heavy and heavy-light chain pairing in the bispecific format.
Recombinant bispecific IgG produced in mammalian cell culture. Knob-into-hole substitutions in the heavy chains drive heterodimerisation; CL/CH1 domain crossover in one arm ensures correct heavy-light pairing. Process details not published.
Reported bioanalytical methods: ELISA for unbound antibody concentration; electrochemiluminescence bridging assay (MSD) for anti-drug antibodies with epitope mapping by competition; modified TZM.bl neutralisation assay for functional ADA inhibition; quantitative flow cytometry for CD4 receptor occupancy.
Excipients & delivery device(s)
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No delivery device
Safety, Efficacy and Evidence Summary
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There are either no relevant patents or these were not yet submitted to LAPaL