Table 1 Selected bispecific antibodies in clinical trials
Developers | Lead molecule | Targets | Technology | Indications | Clinical stage |
|---|---|---|---|---|---|
Trion Pharma, Neovii Biotech a (Munich) | Removab | Epithelial cell adhesion molecule (EpCam) × CD3 | Triomab quadroma technology comprising hybrid mouse IgG2a × rat IgG2b antibody with intact immune effector functions | Malignant ascites | EU approval Apr. 23, 2009 |
Amgen (Thousand Oaks, California) | Blincyto | CD19 × CD3 | Bispecific T-cell engager (BiTE) antibodies comprising different minimal antigen-binding domains from two single-chain Fvs (scFvs) arranged in tandem on a polypeptide chain | Philadelphia chromosome–negative acute lymphoblastic leukemia | FDA approval Dec. 3, 2014 |
Amgen | AMG-110 | EpCam × CD3 | BiTE antibody | Solid tumors | Phase 1 |
AbbVie | ABT-122 | TNF-a x IL-17 | DVD-Ig comprising tetravalent bispecific antibody with two additional variable domains, attached by linkers to the N-termini of the VH and VL domains of a conventional monoclonal antibody | Rheumatoid arthritis | Phase 2 |
AbbVie | ABT-981 | IL-1a × IL-1b | DVD-Ig | Osteoarthritis | Phase 2 |
Affimed Therapeutics | AFM13 | CD30 × CD16A | Tetravalent bispecific tandem diabody (TandAb) comprising four Fv domains joined by peptide linkers | Hodgkin lymphoma | Phase 2 |
Merrimack Pharmaceuticals (Cambridge, Massachusetts) | MM-111 | Human epidermal growth factor receptor 2 (HER2) × HER3 | Bispecific antibody fusion protein comprising two scFv domains linked by modified human serum albumin | Gastric cancer | Phase 2 |
Sanofi (Paris) | SAR156597 | IL-4 × IL-13 | Tetravalent bispecific tandem immunoglobulin (TBTI) | Idiopathic pulmonary fibrosis | Phase 2 |
Roche (Basel) | RG7221 (RO5520985) | Angiopoietin 2 (Ang-2) × vascular endothelial growth factor a (VEGF-A) | Bispecific IgG1 Crossmab antibody based on knob-into-hole mutations and Fab domain exchange | Colorectal cancer | Phase 2 |
Roche, Chugai (Tokyo) | RG6013 (ACE910) | Factor IXa × factor X | Asymmetric bispecific IgG4 antibody | Hemophilia A | Phase 2 |
Genentech (S. San Francisco, California) | RG7597 (MEDH7945A) | Epidermal growth factor receptor (EGFR) × HER3 | Two-in-one IgG1 antibody | KRAS wild-type metastatic colorectal cancer; recurrent/metastatic head + neck cancer | Phase 2 |
Ablynx (Ghent, Belgium), Merck Serono (Darmstadt, Germany) | ALX-0761 | IL-17A × IL-17F | Bispecific nanobody with albumin-binding domain | Autoimmune disease | Phase 2 |
Merus (Utrecht, the Netherlands) | MCLA-128 | HER2 × HER3 | Biclonics full-length bispecific antibody | Solid tumors | Phase 1/2 |
AstraZeneca (London), Amgen | MEDI-565 (AMG-211) | Carincoembryonic antigen × CD3 | BiTE antibody | Gastrointestinal adenocarcinoma | Phase 1 |
Macrogenics, Servier (Suresnes, France) | MGD006 | CD123 × CD3 | Dual-affinity retargeting (DART) bispecific antibody based on two covalently linked Fv polypeptides | Acute myeloid leukemia | Phase 1 |
Regeneron (Tarrytown, New York) | REGN1979 | CD20 × CD3 | Bispecific antibody | Advanced malignancies | Phase 1 |
