Genmab is a biotechnology company focused on developing antibody therapeutics to treat serious diseases, particularly cancer. The company leverages advanced antibody engineering to create innovative medicines. Among these, bispecific antibodies represent a significant area of their work, designed to target two different biological molecules simultaneously. This dual-targeting approach allows for more precise and versatile therapeutic actions compared to traditional antibodies.
Understanding Bispecific Antibodies
Bispecific antibodies are engineered proteins that can bind to two distinct targets at the same time. Unlike naturally occurring antibodies, which typically bind to only one specific antigen, bispecific antibodies possess two unique binding sites. This unique structure allows them to bring two different components into close proximity, such as a cancer cell and an immune cell, or to block two separate disease pathways concurrently.
These “double-targeting” antibodies function by creating a bridge between two different cellular or molecular components. For instance, in cancer treatment, one arm of the bispecific antibody might attach to a protein on a tumor cell, while the other arm binds to a protein on an immune cell, like a T-cell. This connection effectively guides the immune cell to the cancer cell, enabling the immune system to recognize and attack the disease more effectively. This mechanism can also involve blocking two different signaling pathways that contribute to disease progression, offering a more comprehensive therapeutic effect.
Genmab’s Engineering of Bispecifics
Genmab has developed proprietary technologies to engineer their bispecific antibodies. A prominent example is their DuoBody® platform, which enables the creation of bispecific antibodies with a natural antibody structure. This platform generates stable bispecific human IgG1 antibodies through a controlled post-production process.
The DuoBody® technology involves producing two separate IgG1 antibodies, each with a single, matched mutation in their third constant (CH3) domain. These mutations facilitate heterodimerization. After separate production and purification, these “parent” antibody homodimers are reduced in vitro, allowing them to dissociate and then re-oxidize. This controlled Fab-arm exchange process results in the formation of a stable, bispecific antibody with a native IgG1 structure and half-lives similar to natural antibodies. The DuoBody® platform’s efficiency allows for the generation and screening of large libraries of bispecific antibodies, supporting commercial manufacturing scale.
Targeting Diseases with Bispecifics
Genmab’s bispecific antibodies are primarily designed to treat various forms of cancer, with a significant focus on hematologic malignancies and solid tumors. The rationale behind using bispecifics in oncology often involves enhancing immune cell engagement. By bringing immune cells, such as T-cells, into direct contact with cancer cells, these antibodies can redirect and amplify the body’s natural immune response against tumors.
The technology also allows for blocking multiple disease pathways simultaneously, which can be particularly beneficial in complex conditions where single-target therapies may be insufficient. For example, bispecific antibodies can disrupt several signaling pathways that contribute to tumor growth or overcome drug resistance mechanisms. This multi-pronged approach aims to improve treatment efficacy and minimize the ability of cancer cells to evade therapy. While oncology is the primary area, Genmab plans to expand into immunology and other serious diseases, leveraging their antibody platforms.
Key Genmab Bispecific Medicines
Genmab’s pipeline includes several bispecific antibody medicines that demonstrate their technology. One such example is Epcoritamab, co-developed with AbbVie, which targets CD3 on T-cells and CD20 on B-cells. Epcoritamab is being investigated for various B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).
Another significant bispecific antibody is Teclistamab, which targets B-cell maturation antigen (BCMA) on multiple myeloma cells and CD3 on T-cells. This medicine is approved for the treatment of adult patients with relapsed or refractory multiple myeloma. Amivantamab, also co-developed, targets EGFR and MET receptors and is approved for treating non-small cell lung cancer (NSCLC) with specific EGFR exon 20 insertion mutations.