Bispecific & multispecific antibodies

Bispecific and multispecific antibodies are engineered molecules that bind two or more antigens on a single IgG-like scaffold, reaching biology no monospecific antibody can. The dominant class is the T-cell engager: one arm binds CD3 on a T cell and the other a tumour antigen (CD20, BCMA, GPRC5D), forcing an immunological synapse and T-cell killing. Roche’s Lunsumio (mosunetuzumab, CD20xCD3) had its combination with Polivy accepted for FDA supplemental review in relapsed large B-cell lymphoma; Janssen reported Talvey (talquetamab, GPRC5DxCD3) plus Darzalex Faspro data in earlier-line myeloma; Regeneron’s linvoseltamab (BCMAxCD3) BLA was accepted for FDA review; AbbVie’s TEPKINLY (epcoritamab, CD20xCD3) was approved by the European Commission with lenalidomide and rituximab for follicular lymphoma; Genmab (DuoBody platform, epcoritamab co-originator) reported high response rates in elderly DLBCL; and BeiGene released first clinical data on its innovative bispecific.

The key directions of bispecific and multispecific antibodies are:

1. T-cell engagers (T-cell Engager): a CD3 arm recruits polyclonal T cells to a tumour antigen — Roche (Lunsumio, Columvi, CD20xCD3), Janssen (Tecvayli BCMA, Talvey GPRC5D), AbbVie/Genmab (TEPKINLY/epcoritamab CD20xCD3), Regeneron (linvoseltamab BCMA).
2. Dual-antigen co-binding (Dual Targeting): two non-CD3 arms co-target two disease pathways on one molecule, e.g. Roche’s Hemlibra (FIXa/FX) for hemophilia A, and emerging dual-oncology and dual-immunology designs.
3. Bispecific platforms (Bispecific Platform): the proprietary engineering that makes a stable two-arm molecule — Genmab DuoBody, Roche CrossMab/Knob-in-Hole, Regeneron Veloci-Bi, AbbVie/Duomab.
4. Multispecific and format innovation (Multispecific): tri-specifics and novel scaffolds (BiTE, DART) that extend the concept beyond two arms.

Sectoral value chain#

[two antigens / CD3 + tumour] ──> [format design + DuoBody/CrossMab engineering] ──> [stable bispecific drug]
                                              │
                                     (CHO manufacture + CDMO)
                                              │
                                              ▼
[approved off-the-shelf drug] <─── [clinical trial + BLA/MAA] <─────┘

Value chain levels#

Cross-cutting technologies of the sector:

• T-cell engager mechanism (T-cell Engager): the CD3 arm turns every endogenous T cell into a tumour killer, an off-the-shelf alternative to autologous CAR-T that competes for the same CD20 and BCMA targets.
• Bispecific platforms (Bispecific Platform): Genmab DuoBody, Roche CrossMab/Knob-in-Hole and Regeneron Veloci-Bi control correct heavy/light-chain pairing so a single cell makes one stable bispecific product.
• Oncology target selection (Oncology Targets): CD20 (lymphoma), BCMA and GPRC5D (myeloma), DLL3 (small-cell lung) anchor the approved and late-stage pipeline.

The stack pairs dual-target format design with a stable bispecific engineering platform, CHO CMC manufacture, and structured clinical management of T-cell-engager toxicities.

1. T-cell engagers (T-cell Engager):
   • Roche’s Lunsumio (CD20xCD3) plus Polivy is under FDA supplemental review in large B-cell lymphoma, AbbVie/Genmab’s TEPKINLY (epcoritamab) is EC-approved in follicular lymphoma, and Janssen’s Tecvayli/Talvey and Regeneron’s linvoseltamab anchor the myeloma CD3-engager class.
   • The CD3 arm turns endogenous T cells into tumour killers, an off-the-shelf alternative to autologous CAR-T for the same targets.
2. Dual-antigen co-binding (Dual Targeting):
   • Roche’s Hemlibra (emicizumab, FIXa/FX) is the proof-of-concept that a dual-arm non-CD3 bispecific can transform a chronic disease (hemophilia A), and dual-oncology/dual-immunology designs extend the concept.
3. Bispecific platforms (Bispecific Platform):
   • Genmab’s DuoBody controls correct chain pairing so one cell secretes one stable bispecific; Roche’s CrossMab/Knob-in-Hole and Regeneron’s Veloci-Bi are the rival platforms.
4. Multispecific and format innovation (Multispecific):
   • Tri-specifics and fragment scaffolds (BiTE, DART) extend the concept beyond two arms, with BeiGene and others advancing next-generation multispecifics in the clinic.