Since the first monoclonal antibody drug was approved in 1986, antibody-based treatments have disrupted the way diseases are treated. And while monoclonal antibodies will probably always be essential tools in modern medicine, researchers are now exploring the possibilities of multispecific antibodies.
Bispecific antibodies (bsAbs) are antibodies that can attach to two distinct types of antigens simultaneously. bsAbs were first proposed in the late ‘60s, but useful applications were made possible decades later, especially with the development of recombinant DNA technology in the ‘80s and ‘90s.
These antibodies stand out because of their ability to simultaneously engage two different antigens — by binding a cancer cell and an immune cell, bsAbs facilitate a direct and potent immune response against the tumor. Added to that, their design flexibility allows for customization to target specific cancer types, minimizing off-target effects.
And much like they have with other antibody-based treatments like T-cell engagers and ADCs, manufacturers are eager to capitalize on their potential. In 2022, its market size was valued at $5.73 billion, a figure that is expected to rise at a compound annual growth rate of 44% from 2023 to 2030, potentially reaching $110.3 billion by 2030.
With increased activity in bispecific antibody partnerships between key pharma players, FDA approvals and market data pointing to a continued trend, it’s safe to say bispecific antibodies are here to stay.
Two is better than one
Recent market activity hints to drugmakers embracing bispecific antibody technology. In the last few years, pharma giants such as Johnson & Johnson, Sanofi and Genentech have inked partnerships betting on their potential.
In June 2020, Innovent Biologics and Roche inked a $2 billion partnership for the research, development and commercialization of bispecific antibodies and multiple cell therapies targeting hematological and solid cancers. Innovent agreed to pay upfront for development, and commercial milestone payments, as well as royalties, and in exchange will gain access to Roche's technologies for the development of specific 2:1 T-cell bispecific antibodies and the universal CAR-T platform. Roche retained an option to license each product for ex-China development and commercialization, with potential option exercise payments totaling $140 million and additional milestone payments up to $1.9 billion.
Adagene and Sanofi entered into a collaboration and exclusive license agreement in March of 2022 to generate masked monoclonal and bispecific antibodies, with a total potential transaction value of $2.5 billion plus royalties. Adagene was responsible for early-stage research using its SAFEbody technology, while Sanofi handled later-stage research, clinical development, and commercialization. Sanofi made an upfront payment of $17.5 million and had the option to advance two initial antibody candidates, with the potential for two additional candidates.
In December 2022, Akeso announced a collaboration and license agreement with Summit Therapeutics for the bispecific antibody ivonescimab (PD-1/VEGF). Akeso out-licensed exclusive rights to Summit for development and commercialization in the U.S., Canada, Europe, and Japan, while retaining rights for China and other regions. Akeso received a $500 million upfront payment, with the deal's total potential value up to $5 billion, including milestone payments and royalties on net sales.
In December 2022, Sanofi expanded its collaboration with Innate Pharma by licensing a natural killer (NK) cell engager program targeting B7H3 from Innate’s ANKET platform. Sanofi gained exclusive rights to develop, manufacture, and commercialize this program, along with options for two additional targets. Innate received a €25 million ($27 million) upfront payment and could earn up to €1.35 billion ($1.46 billion) in milestone payments plus royalties. This expansion is built on their 2016 collaboration focused on developing bispecific NK cell engagers.
BioNTech and Biotheus inked a partnership with BioNTech responsible for the development, manufacturing, and commercialization of Biotheus' bispecific antibody candidate, PM8002, globally — excluding greater China. Biotheus received $55 million upfront and could get over $1 billion in milestone payments plus tiered royalties. PM8002, currently in phase 2 trials in China, combines anti-PD-L1 and anti-VEGF-A properties, showing promising safety and efficacy in solid tumors.
Elpiscience Biopharma and Astellas Pharma announced a research collaboration and license agreement for the development of novel bispecific macrophage engagers, ES019 and another program. Elpiscience granted Astellas the right to add up to two additional programs and, if exercised, Astellas would have the exclusive rights to research, develop, manufacture, and commercialize these products. Elpiscience received up to $37 million upfront and could potentially receive over $1.7 billion in milestone payments, plus royalties. The collaboration aims to leverage Elpiscience's BiME platform, designed to activate tumor-associated macrophages for cancer immunotherapy.
In March of 2024, Gilead Sciences and Merus announced a collaboration to discover novel trispecific T-cell engager antibodies using Merus' Triclonics platform. Gilead gained an exclusive option to license these therapeutics, intending to leverage their oncology expertise alongside Merus' innovative antibody technology. The partnership focused on developing preclinical research programs targeting dual tumor-associated antigens. Merus' Triclonics platform allows for the creation of antibodies that can bind to three targets simultaneously.
Johnson & Johnson acquired Proteologix to enhance its dermatology capabilities, focusing on immune-mediated diseases. The deal, inked in May of 2024, worth up to $850 million in cash plus potential milestone payments, aimed to expand J&J's portfolio in treating atopic dermatitis (AD) and asthma. Proteologix's key assets included PX128, a bispecific antibody targeting IL-13 and TSLP, and PX130, targeting IL-13 and IL-22. PX128 was set for phase 1 trials for moderate to severe AD and asthma, while PX130 was in preclinical development for AD, targeting multiple disease pathways for high efficacy and infrequent dosing.
In May of 2024, Johnson & Johnson acquired a subsidiary of Numab Therapeutics in a $1.25 billion deal, gaining global rights to NM26, an investigational bispecific antibody for atopic dermatitis (AD). NM26 targets the IL-4R alpha subunit and IL-31 pathways, addressing both skin inflammation and severe itching. AD, the most common inflammatory skin condition, often has treatments that fail to provide lasting remission, affecting about 70% of patients. The dual-targeted approach of NM26 aims to improve both itching and inflammation symptoms.
Up and coming
Currently, many bispecific antibodies are advancing through the pipeline targeting an array of diseases. And since 2020, the FDA has granted approvals to several of these therapies.
- Immunocore Holdings' tebentafusp, approved in January 2022 for HLA-A*02:01-positive patients with unresectable or metastatic uveal melanoma, being the first gp100xCD3 bispecific fusion protein approved for solid tumors.
- Roche's mosunetuzumab, approved in December 2022 for adults with advanced follicular lymphoma whose disease has returned or worsened despite at least two prior treatments, making it the first bispecific antibody approved for any type of non-Hodgkin lymphoma.
- Johnson & Johnson's teclistamab was approved in October 2022 for adult patients with relapsed or refractory multiple myeloma, with durable responses in clinical trials leading to its accelerated approval.
- AbbVie's epcoritamab was approved on May 2023, for adults with diffuse large B-cell lymphoma after at least two lines of systemic therapy and demonstrated promising efficacy and safety in trials.
- Johnson & Johnson's talquetamab was approved on August 2023, for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, under accelerated approval based on response rate and durability of response.
