Table 3.
Genetically engineered bispecific antibodies approved or in clinical development.
| Format | Molecule | Targets | MOA | Indication | Status | Developed by |
|---|---|---|---|---|---|---|
| BiTE | Blinatumomab AMG103 MT103 | CD19 + CD3 | T-cell recruitment | Acute lymphoblastic leukemia | Market | Amgen (Micromet) |
| MT111, AMG211, Medi565 | CEA + CD3 | T-cell recruitment | Gastric cancer advanced adenocarcinoma | 1 | Amgen (Micromet) | |
| Pasotuxizumab MT112 BAY2010112 | PSMA + CD3 | T-cell recruitment | Prostate cancer | 1 | Bayer (Micromet) | |
| Solitomab MT110 AMG 110 | EPCAM + CD3 | T-cell recruitment | Colorectal, lung, GI cancers, solid tumors | 1 | Amgen (Micromet) | |
| AMG420, BI 836909 | BCMA + CD3 | T-cell recruitment | Multiple Myeloma | 1 | Boehringer Ingelheim, Amgen (Micromet) | |
| AMG 330 | CD33 + CD3 | T-cell recruitment | Acute myeloid leukemia | 1 | Amgen (Micromet) | |
| Crossmab (-deriva-tives) | Vanucizumab RG7221 (1+1) | Angiopoietin 2 + VEGF | 2-Ligand inactivation | Colorectal cancer | 2* | Roche |
| RG7716 (1+1) | Angiopoietin 2 + VEGF | 2-Ligand inactivation | Wet AMD | 2 | Roche | |
| RG7802 (2+1) | CEA+CD3 | T Cell recruitment | CEA pos. solid tumors | 1 | Roche | |
| RG7386 (2+2) | FAP+DR5 | targeted apoptosis | Solid tumors | 1 | Roche | |
| DVD-Ig | ABT165 | DLL4+VEGF | 2-Ligand inactivation | Adv solid tumors | 1 | Abbvie |
| Remtolumab ABT122 | TNFalpha+IL17 | 2-Ligand inactivation | Psoriatic arthritis | 2* | Abbvie | |
| Lutikizumab ABT981 | IL1a + IL1b | 2-Ligand inactivation | Osteoathritis | 2 | Abbvie | |
| SAR156597 DVD-Ig like TBTI | IL4 + IL13 | 2-Ligand inactivation | Idiopath pulm. Fibrosis | 2 | Sanofi | |
| TandAb | AFM111 | CD19+CD3 | T-cell recruitment | Non Hodkins Lymphoma, Acute lymphoblastic leukemia | 1 | Affimed |
| AFM113 | CD30+CD16A | Immune cell recruitment | Hodkins disease | 2 | Affimed | |
| DART | MGD006 S80880 | CD123 + CD3 | T-cell recruitment | AML | 1 | Macrogenics, Servier |
| MGD007 | GPA33 + CD3 | T-cell recruitment | Colorectal cancer | 1 | Macrogenics, Servier | |
| MGD010 | CD32B + CD79B | B-cell modulation | Immune diseases | 1 | Macrogenics, Takeda | |
| PF06671008 | P cadherin + CD3 | T-cell recruitment | Solid tumors | 1 | Pfizer, Macrogenics | |
| MGD009 | B7H3 + CD3 | T-cell recruitment | Solid Tumors | 1 | Macrogenics | |
| Duvortuxizumab, MGD 011, JNJ64052781 | CD19+CD3 | T-cell recruitment | Solid Tumors | 2 | Macrogenics, Janssen | |
| Bi-nanobody | BI836880 | VEGF+Ang2 | 2-Ligand inactivation | Solid tumors | 1 | Ablynx, Boehringer Ingelheim |
| BI1034020 | beta amyloid 40 + 42 | 2-protein inact | Alzheimers | 1* | Ablynx & Boehringer Ingelheim | |
| ALX0761 | IL17A + IL17F | 2-Ligand inactivation | Inflammatory disease | 1 | Ablynx, Merck Serono | |
| Vobarilizumab ALX0061 | IL6R+albumin | PK-modulated receptor antagonist | Lupus, rheumatoid arthritis | 2 | Abbvie, Ablynx | |
| Ozoralizumab ATN103 | TNF+albumin | PK-modulated ligand antagonist | Rheumatoid arthritis | 2 | Ablynx, Taisho, Eddingpharm | |
| cLC-hetero-H-chain IgG | Emicizumab, ACE910, RG6013 | FXI + FX | 2-Factor dimerization | Hemophilia A | 3 | Chugai, Roche |
| MCLA117 | CLEC12A+CD3 | T-cell recruitment | Acute myeloid leukemia | 1/2 | Merus | |
| MCLA128 | Her2+Her3 | 2-RTK inactivation | Solid tumors | 1/2 | Merus | |
| REGN1979 | CD20+CD3 | T-cell recruitment | B-cell cancer | 1 | Regeneron | |
| Navicixizumab OMP-305B83 | DLL4+VEGF | 2-Ligand inactivation | Solid tumors | 1 | Oncomed, Celgene | |
| ERY974 | GPC3+CD3 | T-cell recruitment | Solid tumors | 1 | Chugai | |
| IgG assembled from half-antibodies bsmAb bsmAb | ZW25 (Azymetrics) | Her2 | RTK-inactivation | Her2 pos. cancer | 1 | Zymeworks |
| RG7828, BTCT 4465A (KiH) | CD20+CD3 | T-cell recruitment | Non-Hodgkin's lymphoma, CLL | 1 | Genentech | |
| JNJ 63709178 Duobody | CD123+CD3 | T-cell recruitment | Acute myeloid leukemia | 1 | Janssen, Genmab | |
| JNJ 61186372, EM1 Duobody | Her1+cMet | 2 RTK inactivation | Non-small-cell lung cancer | 1 | Janssen, Genmab | |
| RG7990 BITS7201A | IL13+IL17 | 2 ligand inactivation | Asthma | 1 | Genentech, Novimmune | |
| RG7992, BFKB8488A | FGFR1+KLB | Hormone (FGF21) mimetic | type 2 diabetes | 1 | Genentech | |
| scFv-Fc-(Fab) -fusions | Xmab14045 Fab-scFv-Fc | CD123+CD3 | T-cell recruitment | Acute myeloid leukemia | 1 | Xencor, Novartis |
| GBR1302 Fab-scFv-Fc | Her2+CD3 | T-cell recruitment | Her2 pos. cancer | 1 | Glenmark | |
| MOR 209, ES414 ScFv2-Fc-scFv2 | PSMA+CD3 | T-cell recruitment | Prostate cancer | 1 | Morphosys, Emergent Biosolutions | |
| Istiratumab MM141, IgG-scFv | IGF1R + Her3 | 2-RTK inactivation | Adv. solid tumors | 2 | Merrimack | |
| IL-17/IL-34 biAb scFv-Fc | IL23 + IL17 | 2-Ligand inactivation | Inflamm. & Autoimm. disease | 1 | BMS (Zymogenetics) | |
| LY3164530 IgG+scFv | Her1 + cMET | 2-RTK inactivation | solid tumor | 1 | Eli Lilly | |
| MM111 scFv2-BSA | Her2 + Her3 | 2-RTK inactivation | Adv. gastric esoph. cancer | 2* | Merrimack | |
| MEDI3902 Fab-scFv-Fc | PsI + PcrV | 2 antigen inactivation | Pneumonia | 2 | Medimmune | |
| MEDI7352 | NGF+TNF | 2 ligand inactivation | Osteoarthritis | 1 | Medimmune | |
| MEDI0700 | BAFF+B7RP1 | 2 ligand inactivation | Lupus | 1 | Medimmune | |
| bsmAb | LY3114062 | TNF+IL17 | 2 ligand inactivation | Rheumatoid arthritis | 1 | Eli Lilly |
| DAF-IgG | Duligotuzumab RG7597 | Her1 + Her3 | 2-RTK inactivation | Head & neck, colorectal cancer | 2 | Genentech |
| D&L Fab3 | TF2 IMP288 | CEACAM5 + hapten | Payload delivery | Colorectal, lung cancer | 1/2 | Immunomedics |
Note: Additional bsAb-related entities in clinical development that are not listed in this table include JNJ 61178104 (undisclosed targets in inflammation, Ph1, Genmab/Janssen-Duobody); VM100 (Ab40&42 ‘bispecific/crossreactive’ normal mAb, Ph1 in macular degeneration, Vision Medicine); MEDI4276 (bi-Her2-tubulysin ADC, Ph1 Medimmune); Bi-EGFR targeted minicell-nanoparticles (EnGene, Ph1 in cancer) and OXS1550/DT2219ARL, a CD19+CD22 targeted truncated diphtheria toxin (Oxis Biotech, Ph1/2 in leukemia and lymphoma) and AMG570, a bispecific peptibody conjugate targeting BAFF and ICOSL (Amgen/AstraZeneca, Ph1) * completed studies to our knowledge.