The year of the bispecific in oncology and beyond

While 2025 has not been a banner year for biopharma dealmaking, antibodies that bind two or more molecular targets—so-called multispecifics—have taken center stage. The top three licensing deals and the second-largest merger of the year to date all involve bispecific assets (Table 1). And while most of the licensing and research partnership deals for bispecific therapeutics have focused on precision oncology, across industry autoimmune disease is also attracting interest.

A notable trend among these deals is the disproportionate number of assets acquired from Chinese companies. China’s biotechs are gaining a reputation for antibody-engineering prowess, and “a key advantage for Chinese programs is their ability to rapidly and cheaply gain ‘proof of signal’ in a small human trial,” said Leon Tang, founder and scientific advisor of InScienceWeTrust (ISWT) BioAdvisory. Indeed, the past year has seen bispecific antibodies take the spotlight from antibody–drug conjugate (ADC) oncology assets and technologies, which dominated the conversation in previous years.

Less for more

Over the past 12 months, biopharma dealmaking transactions fell to overall levels not seen since 2016. According to DealForma, 215 deals were announced across the industry in the first 10 months of 2025, down from 317 in 2024 and 298 in 2023. However, the top five therapy areas—oncology, neurology, infectious disease, autoimmunity, and endocrinology/metabolism (Fig. 1)—generated $12.3 billion, roughly on a par with the previous three years.

Oncology has experienced a steep drop in transactions. By October 2025, the industry had seen only 105 deals compared with 175 in 2024 and 162 in 2023 (Fig. 1). Yet each of those licenses generated on average $47.6 million—a 30% increase over the previous year ($36.6 million).

For merger and acquisition (M&A) transactions in 2024–2025 around cancer therapeutics, just 26 announcements were made in the first 10 months of this year, compared with 36 last year in its entirety. With multinational pharmaceutical companies facing a patent cliff, analysts have been predicting greater M&A activity; indeed, biopharma buyers are paying more, on average $1.1 billion per M&A deal this year compared with $475 million per deal last year. Cancer remains the dominant dealmaking category, accounting for more than a third of all 2024 biopharma transactions in both number and total value (Fig. 2).

Of the big biopharma companies, Roche, AstraZeneca, and AbbVie have been very active across the dealmaking landscape, clinching billion dollar deals in cancer. In January 2025, Roche closed its $1.5 billion acquisition of chimeric antigen receptor T-cell (CAR-T) therapy developer Poseida Therapeutics. AbbVie signed a ~$2.2 billion deal around bispecific T-cell engagers with Xilio Therapeutics in February. And in March, AstraZeneca agreed to pay up to $1 billion for the in vivo CAR-T therapy pioneer EsoBiotec.

However, other big players have also made splashes. Banner M&A deals included Eli Lilly and Company’s $2.5 billion takeover of Scorpion Therapeutics in January; Merck KGaA’s $3.4 billion enterprise value ($3.9 billion equity value) acquisition of SpringWorks Therapeutics, which concluded in July; and Sanofi’s $9.5 billion acquisition of Blueprint Medicines, which was announced in June.

The Scorpion Therapeutics deal gives Lilly an oncology beachhead around STX-478, a once-daily, oral, mutant-selective phosphatidylinositol 3 kinase alpha (PI3Kα) inhibitor program for breast cancer and other advanced solid tumors. As part of the agreement, Scorpion spun out Antares Therapeutics, with a $177 million funding round (Lilly took a minority equity interest) and the sale of two epidermal growth factor receptor (EGFR) inhibitors to Scorpion’s partner Pierre Fabre.

Merck KGaA’s takeover of SpringWorks provides the German pharma access to a Hippo signaling pathway inhibitor (SW-682) and a molecular glue degrader (SW-3431) against protein phosphatase 2 (PPP2R1A)-mutant uterine cancer in early development. But here, the main deal drivers were two US Food and Drug Administration (FDA)-approved therapies. SpringWorks’ flagship product, Ogsiveo (nirogacestat), is a small-molecule gamma-secretase complex inhibitor that blocks proteolytic activation of the Notch receptor. The drug is approved for use against adult desmoid tumors, and is also in phase 2 trials for pediatric desmoid tumors, ovarian granulosa cell tumors, and relapsed/refractory multiple myeloma. And Gomelki (mirdametinib) is a small-molecule inhibitor of mitogen-activated protein kinase 1 (MEK1) and MEK2, which are upstream regulators of the extracellular signal-related kinase (ERK) pathway. It is approved for patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas.

The Blueprint deal gave Sanofi access to Ayvakit (avapritinib), a small-molecule inhibitor of the receptor tyrosine kinase c-KIT that is approved to treat gastrointestinal stromal tumors, indolent systemic mastocytosis, and advanced systemic mastocytosis. The pharma company also gained access to other wild-type or selective c-KIT mutant small-molecule inhibitors in late-stage development for systemic mastocytosis, chronic urticaria, allergic rhinoconjunctivitis, allergic asthma, and mast-cell-activation syndrome, together with some protein degraders targeting cyclin-dependent kinase 2 (CDK2) and CDK4 in discovery.

Interestingly, other established biopharma companies such as J&J and Regeneron have yet to make a cancer deal in 2025.

Bispecifics to the spotlight

Bispecific antibodies were involved in six of the top 20 R&D licensing partnerships from January to October 2025, many targeting oncology (Table 1).

This activity has three main drivers, according to Matt Phipps, partner and group head of biotechnology equity research at the investment bank William Blair.

“One is simply business-driven,” he said. “You can make a bispecific to two known targets as the parental monoclonals go off market exclusivity.” This provides companies with a simple strategy to extend their antibody franchises.

Another driver is proof-of-principle clinical data showing that two targets combined in a disease pathomechanism could improve clinical outcomes. According to Phipps, the 2022 readout from the Johnson & Johnson VEGA phase 2a clinical trial—which combined guselkumab (an interleukin-23 inhibitor) and golimumab (a tumor necrosis factor alpha inhibitor) in ulcerative colitis—was a landmark event. “That was a clear signal that you have a therapeutic window to get added benefit by going after two validated immunology targets,” he said. The J&J dataset opened a wave of enthusiasm that bispecifics were a go-to approach “whether you’re going after two soluble cytokines, a receptor and a cytokine, two receptors, cis-targeting, or all of these other combinations”.

A further driver, according to Phipps, was the approval of a T-cell engager against small-cell lung cancer. “With Amgen’s Imdelltra (tarlatamab), we finally had a breakthrough drug approval in a solid tumor. That really launched the pursuit of T-cell engagers,” he said.

AbbVie has been particularly active in the area in 2025, making deals with Simcere Zaiming, Xilio Therapeutics, and IGI Therapeutics that add up to a potential outlay on T-cell engager assets of ~$5.1 billion, with >$752 million in upfront fees.

In the deal in January with Simcere Zaiming, AbbVie committed an undisclosed upfront payment and potentially up to $1.055 billion to license the Chinese company’s phase 1-stage cancer therapy candidate SIM0500, a tri-specific antibody that targets GPRC5D and BCMA, in addition to CD3 on T cells. AbbVie’s partnership with Xilio, signed in February, aims to develop up to four novel immunotherapies using the latter’s masked T-cell engager antibodies. Xilio received $52 million upfront, and is eligible for up to $2.1 billion in contingent payments and $1.8 billion in development, regulatory, and commercial milestones, plus royalties. And in July, IGI Therapeutics received $700 million upfront for granting AbbVie exclusive rights to develop, manufacture, and commercialize ISB-2001, a CD38 × B-cell maturation antigen (BCMA) × CD3 tri-specific T-cell engager currently in phase 1 for relapsed/refractory multiple myeloma. IGI Therapeutics is eligible to receive up to $1.225 billion in development, regulatory, and commercial milestones, plus double-digit tiered royalties.

One month later, Excalipoint paid Lepu Biopharma $10 million upfront for access to two undisclosed bispecific T-cell engagers. With contingency payments, commercial milestones, and royalties, the total deal value could rise to $858 million.

In September 2025, Genmab’s $8 billion acquisition of Merus became the second largest M&A deal of the year. The Denmark-based antibody maker gobbled up several of Merus’ assets: FDA-approved Bizengri (zenocutuzumab-zbco), a bispecific antibody targeting human epidermal growth factor receptor 2 (HER2) and HER3 for adenocarcinoma and non-small-cell lung cancer; petosemtamab (MCLA-158), a bispecific antibody targeting EGFR and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), in phases 2 and 3 for colorectal cancer, and head and neck cancer, respectively; MCLA-129, a bispecific antibody targeting EGFR and c-MET, in phase 2 for solid tumors; ONO-4685, a PD-1 × CD3 T-cell engager for relapsed/refractory T-cell lymphoma and psoriasis, in phase 2; and several earlier-stage assets.

In October, Takeda forked out $11.4 billion to Innovent Biologics to gain access to its oncology bispecifics in the clinic. Through this deal, Takeda accesses Innovent’s PD-1 × IL-2^α-bias-targeting bispecific antibody (IBI363) alone, and an ADC comprising an anti-claudin 18 isoform A2 (CLDN18.2) monoclonal antibody conjugated to the DNA topoisomerase I inhibitor exatecan (IB1343) for gastric and pancreatic cancers.

Overall, looking across the entire landscape, some of the most common targets for the licensed bispecific antibodies included PD-1, vascular endothelial growth factor (VEGF), BCMA, HER2, and HER3, in addition to CD3 for T-cell engagement. In terms of novel targets, Novatim Immune Therapeutics’ $1.2 billion deal with Radiance Biopharma in September focused on a bispecific targeting c-MET and EGFR; Qyuns Therapeutics $1.1 billion deal with Roche in October centered around a bispecific antibody against thymic stromal lymphoprotein (TSLP) and IL-33; and EpiMab Therapeutics $210 million deal with Juri Biosciences in May was for a bispecific T-cell engager targeting human kallikrein 2 (KLK2) and CD3.

All in all, eight of the 14 deals struck for multi-specific antibodies in 2025 involved T-cell engagers, either bispecifics or trispecifics (Table 1). This is a therapeutic mechanism that is now firmly established in oncology (and is also gaining ground in autoimmunity). Over 40% (7/16) of pharma’s multi-specific deals from July 2024 to June 2025 were in autoimmune or inflammatory diseases, with bispecific or trispecific T-cell engagers targeting CD19, CD20 or BCMA on pathogenic B cells or plasma cells.

The rise of bispecifics as the pre-eminent therapeutic modality signals a coming of age for the technology. In 2024, Amgen’s ImDelltra (tarlatamab; CD3 × DLL3), Jazz Pharmaceuticals’ Ziihera (zanidatamab; a biparatopic HER3), Merus’ Bizengri (zenocutuzumab; HER2 × HER3), and Regeneron Pharmaceuticals’ Ordspono (odronextamab; CD3 × CD20) all received approvals in the United States or Europe. This lengthening track-record of FDA approvals and positive clinical readouts, together with the promise of additional functionality and better therapeutic windows, has made this modality increasingly attractive to buyers.

Other winners from the past year are proximity-induced degraders and molecular glues. Four of the top 20 biopharma licensing deals this year (those between XtalPi and DoveTree, Oronis Biosciences and Genentech, Neomorph and AbbVie, and Magnet Biomedicine and Eli Lilly) involved molecular glues. Now that proof-of-concept data have been generated for targets such as androgen and estrogen receptors in breast cancer, many of the deals revolved around new targets for the modality, such as signal transducer and activator of transcription 6 (STAT6), CDK2, EGFR, and VAV1.

Finally, there has been a steady drip of deals around in vivo CAR-T therapies. Since December 2024, AstraZeneca, AbbVie, Gilead, and Bristol Myers Squibb (BMS) have paid out a total of >$4.8 billion to acquire EsoBiotec, Capstan Therapeutics, Interius Therapeutics, and Orbital Therapeutics, respectively. Gilead’s Kite Pharma subsidiary also signed a deal focused on in vivo CAR-based cell therapies with Pregene Biopharma in October 2025 that could be worth up to $1.64 billion to the Chinese biotech.

The China factor

The past year continued to see voracious demand for Chinese assets, with biotech-to-biotech transactions a growing driver, following the precedent set by big pharma in previous years. According to Biocentury, from July 2024 to July 2025, multinationals spent >$4 billion in upfront payments for partnerships and licensing deals involving assets from Chinese biopharma companies.

And given the traditional strength of Chinese biopharma in antibody engineering, it is striking how many of these deals focused on bispecific and multispecific antibodies. According to Tang, “This plays to Chinese R&D strengths. There’s a lot of iteration around bispecific assets and combinations of targets. And Chinese companies are really strong in protein and antibody engineering.”

All told, 10 deals paid out a total of >$2.6 billion in upfront fees to Chinese companies developing the therapeutic modality. T-cell engagers are again to the fore, adding up to six of the 10 deals.

According to Pharmaprojects, China has now overtaken Europe as a source of new-to-pipeline drugs, with South Korea also leapfrogging the UK and Switzerland. Most of the Chinese programs that were deal targets involved well-validated cancer targets like BCMA, CD19, VEGF, and EGFR. However, KLK2, GPRC5D, TSLP, and IL-33 are all targets outside of the traditional cancer realm, perhaps signaling a shift towards research and development on autoimmune disease drugs in China, where cancer has previously dominated.

Outlook

Even in a year when overall deal volume sagged, bispecifics have emerged as the strategic through-line: fewer transactions, bigger checks, and broader ambition. The top licensing deals treat bispecifics not as niche bolt-ons but as potential backbone therapies spanning multiple solid tumors—and, increasingly, immune-mediated disease. China’s engineering muscle has been pivotal to this shift, supplying validated PD-1 × VEGF and BCMA × CD3 engines alongside a growing crop of non-oncology targets (TSLP, IL-33, and KLK2).

“One area I would keep an eye on is bispecific ADCs,” said Tang. Phipps also pointed to upcoming clinical readouts for new mechanisms: “Everyone’s always looking for new targets for T-cell engagers. I think that the clinical data in ovarian cancer suggest that claudin 6 (CLDN6) is going to be important; and in renal carcinoma, there’s a lot of anticipation for readouts around T-cell engagers targeting ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3).”

Whether the bispecific momentum persists into 2026 and beyond will depend on whether clinical data position next-generation agents to supplant existing single-target monoclonal antibody franchises. Cross-border licensing should remain brisk as multinationals bridge patent cliffs, and Chinese developers monetize speed and scale, leveraging their ability to obtain early human ‘proof of signal’ data in investigator-initiated trials. If those boxes get ticked, the ‘year of the bispecific’ won’t read as a blip in a down market—it will mark the start of a new default modality.