Bispecific antibody companies: What companies are developing bispecific drug products?

Leading biopharmaceutical companies are at the forefront of bispecific antibody development, driving innovation in therapies for cancer, autoimmune diseases, and more. These companies are developing groundbreaking bispecific drugs that offer enhanced precision and efficacy, revolutionizing the way complex diseases are treated.

We will take a closer look at some of the companies that have been shaping the bsAb industry by developing and producing innovative bispecific drug products.

Bispecific antibodies – how do they draw attention?

BsAbs have garnered significant attention in the biopharmaceutical industry due to their unique ability to simultaneously bind two different antigens. This allows bsAbs to address complex disease mechanisms, often more effectively than traditional monoclonal antibodies.

One of the most notable applications of bsAbs is in oncology. For instance, blinatumomab (Blincyto®), an FDA-approved bsAb, targets CD19 on B-cell malignancies and CD3 on T-cells, bringing these immune cells into close contact with cancer cells to target their cytotoxic effects.¹

In hematology, emicizumab (Hemlibra®) has revolutionized the treatment of hemophilia A by bridging activated Factor IXa and Factor X, mimicking the function of the missing Factor VIII.² This bsAb significantly reduces bleeding episodes and improves patient quality of life, showcasing the therapeutic versatility of bsAbs beyond oncology.

The future potential of bsAbs extends beyond current FDA-approved applications. Ongoing research is exploring their use in autoimmune diseases, infectious diseases, and even neurological disorders.³

The bispecific antibody market – an overview

The global bsAbs market is experiencing significant growth, in part driven by the increasing prevalence of chronic diseases such as cancer and autoimmune disorders.⁴

In 2022, the market size was valued at approximately USD 5.73 billion and projected to grow at a compound annual growth rate (CAGR) of 44.0% from 2023 to 2030.⁵

Companies producing bsAb drugs approved by the FDA

In this section, we will focus on bispecific antibody companies that have successfully brought FDA-approved bsAb drugs to market. These companies have, among others, demonstrated their leadership in biopharmaceutical innovation by developing therapies that target complex diseases with high efficacy.

Please note, though, that the list might not be exhaustive, considering the ongoing developments and achievements on the bsAb market.

Amgen

Amgen, headquartered in Thousand Oaks, California, is a pioneer in the field of bsAbs, with blinatumomab (Blincyto®) being one of the first bsAbs to receive FDA approval back in 2014. Blinatumomab targets CD19 on B-cell malignancies and CD3 on T-cells, facilitating a direct immune attack on cancer cells.¹ This bsAb has significantly improved treatment outcomes for patients with CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL).

In May 2024, the FDA also granted accelerated approval to Amgen’s tarlatamab (Imdelltra®) for treatment of extensive stage small cell lung cancer (SCLC).⁶ Tarlatamab simultaneously targets delta-like ligand 3 (DLL3, overexpressed on SCLC cells) and CD3. ⁷This bsAb represents a novel treatment option for a particularly aggressive form of lung cancer following chemotherapy.

Roche and Genentech

Roche, based in Basel, Switzerland, and its subsidiary Genentech, headquartered in South San Francisco, California, have made substantial contributions to the bsAb landscape. Emicizumab (Hemlibra®) is a notable example, approved for treating hemophilia A. Emicizumab bridges activated Factor IXa and Factor X, mimicking the function of missing Factor VIII, and thereby significantly reducing bleeding episodes in patients.²

Roche has also made strides in the treatment of retinal vascular disease with faricimab (Vabysmo®), FDA-approved in 2022. Faricimab is designed to treat ocular conditions like wet age-related macular degeneration (AMD) and diabetic macular edema (DME) by targeting both VEGF-A and Angiopoietin-2. This dual targeting helps reduce abnormal blood vessel growth and stabilize existing vessels, improving visual outcomes for patients.⁸

Finally, glofitamab (Columvi®) and mosunteuzumab (Lunsumio®) are both CD20/CD3-targeting bsAbs managed by Roche for treatment of B cell malignancy. They are currently approved for various forms of B-cell lymphoma.^910,

Immunocore

Immunocore, headquartered in Abingdon, Oxfordshire, UK, has developed tebentafusp (Kimmtrak®), a bsAb targeting gp100 peptide – an antigen found on uveal melanoma tumor cells – and CD3.¹¹ This approval marks a significant milestone in the treatment of this rare and aggressive form of eye cancer.

Janssen Biotech

Janssen Biotech, headquartered in Horsham, Pennsylvania and part of Janssen Pharmaceuticals (now known as Johnson & Johnson Innovative Medicine), has also made significant strides in bsAb development. Janssen Biotech began a collaboration with Genmab (based in Copenhagen, Denmark) in 2012, developing bsAbs using the latter’s proprietary DuoBody technology. ¹²The first success of this partnership was realized in 2021 with regulatory approval of amivantamab (Rybrevant®). This bsAb targets EGFR and MET, providing a new therapeutic option for patients with non-small cell lung cancer (NSCLC).¹³ Amivantamab’s ability to inhibit multiple pathways involved in tumor growth underscores its potential in oncology. Further Duobody successes from Janssen Biotech include talquetamab (Talvey®) and taclistamab (Tecvayli®), both CD3 T-cell engagers for treatment of relapsed/refractory multiple myeloma.^,1415

AbbVie

AbbVie, based in North Chicago, Illinois, has also utilized the DuoBody platform to develop epcoritamab (Epkinly®), targeting CD20 expressed on B cell malignancies and CD3 on T cells. This bsAb is approved for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), demonstrating significant efficacy in this challenging hematologic malignancy.¹⁶ It has also recently been approved for treatment of relapsed/refractory follicular lymphoma.¹⁷

Pfizer

Pfizer, based in New York, New York, received accelerated FDA approval in 2023 for their drug elranatamab (Elrexfio®). It targets BCMA – a B-cell maturation antigen – and CD3, designed as a treatment option for patients with multiple myeloma who have undergone multiple lines of prior therapy.¹⁸

Companies engaged in bispecific antibody development – a selection

The development of bsAbs is a rapidly growing field, with numerous companies investing in innovative research to create new therapeutic options.

Here is a selection of additional notable companies actively engaged in bsAb development apart from those that have already gained FDA approval (although many of them keep investigating in this fascinating sector, too):

evitria

evitria specializes in the rapid and efficient production of various antibody products. We provide advanced bsAb expression services, leveraging transient transfection of CHO cells. Recently, evitria entered into a license agreement with Lonza to access their bYlok® bispecific pairing technology,¹⁹ enhancing our capability to produce functional bsAbs by ensuring correct heavy-light chain pairing. See more on evitria in the chapter below.

Akeso

Akeso is a biotechnology company focused on developing next-generation immunotherapies, including bsAbs. Their pipeline includes bsAbs designed to target multiple pathways in cancer and autoimmune diseases, several of which are approved for use in China, including cadonilimab, ivonescimab and penpulimab. Their production pipeline leverages a proprietary Tetrabody technology which enables production of tetravalent bsAbs.²⁰

Lonza

Lonza is a prominent CDMO player in the development and production of bsAbs. Alongside their unique bYlok® heavy-light chain pairing technology,¹⁸ Lonza offers comprehensive services that support bsAb development from discovery to IND filing.²¹

Xencor

Xencor specializes in engineering antibody and cytokine therapeutics. Their XmAb® technology modifies Fc domains to introduce various enhanced features such as improved natural killer cell activation, immune inhibition through B cell signaling, or extended half-life through interactions with FcRn receptor. Xencor’s pipeline includes bsAbs targeting various cancers and autoimmune diseases.²²

Alphamab Oncology

Alphamab Oncology is dedicated to the research and development of innovative antibody therapies for cancer treatment. Their CRIB (Charge Repulsion Induced Bispecific) platform aims to promote heterodimerization and thereby overcome challenges in bsAb production by introducing point mutations to induce changes in charge. ²³They have developed a robust pipeline of bsAbs, including KN046, which targets PD-L1 and CTLA-4 on tumor infiltrating lymphocytes, and KN026, which targets two non-overlapping epitopes of HER2 for dual signal blockade.²⁴

Regeneron

Regeneron is a biotechnology company with a diverse portfolio of therapeutic development, including biologics and genetic medicines. Regeneron has developed a number of bsAbs currently in clinical trials, including linvoseltamab and odronextamab. Both are T cell engagers directed to BCMA and CD20 to treat multiple myeloma and lymphoma, respectively.²⁵

Bispecific antibody development and production at evitria

evitria is at the forefront of bispecific antibody development and production, providing specialized services to research groups, pharmaceutical manufacturers, and CDMOs. Utilizing cutting-edge recombinant DNA technology and CHO cells as expression system of choice, evitria ensures the efficient and high-quality production of bsAbs.

Our expertise in using CHO cells for transient transfection processes guarantees robust and scalable antibody production. By offering customized bispecific antibody expression services, evitria supports the creation of tailored therapeutics that meet specific research and clinical needs. This enables the development of bsAbs in various formats, including CrossMab, Knobs-into-Hole, and Genmab’s Duobody system.

Furthermore, evitria has recently entered a license agreement with Lonza, making us the first company apart from Lonza to use its bYlok® technology. This allows us to express bsAbs with more than 95% correct heavy-light chain (HC-LC) pairing, with advantages like facilitated lead candidate identification.
With profound expertise in recombinant antibody production, evitria is a trusted partner in the advancement of bispecific antibody technology.

Read more about Bispecific Antibodies from Desmond Schofield

• Bispecific antibody production – A comprehensive overview
• Bispecific Antibody Expression Service
• Bispecific antibodies – comprehensive overview
• Understanding the side effects of bispecific antibodies
• Development of bispecific antibodies
• How to choose a bispecific antibody format?
• Bispecific antibody formats
• FDA approved bispecifc antibodies

Sources

1. Blincyto®. Prescribing information. Amgen Inc; 2018. Accessed June 14, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125557s013lbl.pdf ↩︎
2. Hemlibra®. Prescribing information. Genentech Inc; 2024. Accessed June 27, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761083s018lbl.pdf ↩︎
3. U.S. Food And Drug Administration. Bispecific Antibodies: an area of research and clinical applications. Published February 14, 2024. Accessed June 14, 2024. https://www.fda.gov/drugs/spotlight-cder-science/bispecific-antibodies-area-research-and-clinical-applications.  ↩︎
4. Conrad N, Misra S, Verbakel JY, et al. Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK. Lancet. 2023;401(10391):1878-1890. doi:10.1016/s0140-6736(23)00457-9 ↩︎
5. Grand View Research. Bispecific Antibodies Market Size, Share & Trends Analysis Report By Indication (Cancer, Inflammatory & Autoimmune disorders), By Region (North America, Europe, Asia Pacific), And Segment Forecasts, 2023 – 2030. https://www.grandviewresearch.com/industry-analysis/bispecific-antibodies-market-report. ↩︎
6. U.S. Food And Drug Administration. FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. Published May 16, 2024. Accessed July 9, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer. ↩︎
7. Imdellra®. Prescribing information. Amgen Inc; 2024. Accessed July 9, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761344s000lbl.pdf ↩︎
8. Vabysmo®. Prescribing information. Genentech Inc; 2022. Accessed June 14, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761235s000lbl.pdf ↩︎
9. Columvi®. Prescribing information. Genentech Inc; 2023. Accessed July 9, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761309s000lbl.pdf ↩︎
10. Lunsumio®. Prescribing information. Genentech Inc; 2022. Accessed July 9, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761263s000lbl.pdf ↩︎
11. Kimmtrak®. Prescribing information. Immunocore Limited; 2022. Accessed July 9, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761228s000lbl.pdf ↩︎
12. Johnson & Johnson. Janssen Biotech Announces Global License and Development Agreement for Investigational Anti-Cancer Agent Daratumumab. https://www.jnj.com/media-center/press-releases/janssen-biotech-announces-global-license-and-development-agreement-for-investigational-anti-cancer-agent-daratumumab. Published August 30, 2012. Accessed July 9, 2024. ↩︎
13. Rybrevant®. Prescribing information. Janssen Biotech, Inc; 2021. Accessed July 9, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761210s000lbl.pdf ↩︎
14. Talvey®. Prescribing information. Janssen Biotech, Inc; 2023. Accessed July 9, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761342s000lbl.pdf ↩︎
15. Tecvayli®. Prescribing information. Janssen Biotech, Inc; 2023. Accessed July 9, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761291s000lbl.pdf ↩︎
16. Epkinly®. Prescribing information. Genmab US, Inc and AbbVie, Inc; 2023. Accessed July 9, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761324s000lbl.pdf ↩︎
17. U.S. Food And Drug Administration: FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory follicular lymphoma. Published June 26, 2024. Accessed July 9, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-follicular-lymphoma#:~:text=On%20June%2026%2C%202024%2C%20the,more%20lines%20of%20systemic%20therapy. ↩︎
18. Elrexfio®. Prescribing information. Pfizer Inc; 2023. Accessed July 9, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761345Orig1s000lbl.pdf ↩︎
19. bYlok® bispecific pairing technology. Lonza. Accessed June 25, 2024. https://www.lonza.com/biologics/expression-technologies/bYlok ↩︎
20. Akseo, Inc | Technology Platform. Akeso, Inc. https://www.akesobio.com/en/rd-and-science/rd-platform. Accessed July 9, 2024. ↩︎
21. Ibex® Design Bispecifics DNA-to-IND Program. Lonza. https://www.lonza.com/biologics/mammalian/ibex-design-bispecific-antibodies. Accessed July 9, 2024. ↩︎
22. Xencor | Pipeline. Xencor. https://xencor.com/pipeline. Accessed July 9, 2024. ↩︎
23. Proprietary Bispecific Platform. Alphamab Oncology. https://www.alphamabonc.com/en/technology/bispecific.html. Accessed July 9, 2024. ↩︎
24. Pipeline Overview. Alphamab Oncology. https://www.alphamabonc.com/en/pipeline/overview.html. Accessed July 9, 2024. ↩︎
25. Regeneron Pharmaceutical’s Research and Development Pipeline. Regeneron. https://www.regeneron.com/pipeline-medicines/investigational-pipeline. Accessed July 9, 2024. ↩︎