BD transactions for trispecific antibodies are evolving from sporadic sparks into a sweeping fire.

On April 27, 2026,beijing Huahui Anjian BioScience and BeiGene entered into a global exclusive option, license, and collaboration agreement for HH160, a trispecific antibody targeting PD-1, CTLA-4, and VEGF-A.

Under the agreement, BeiGene paid a 20 million upfront payment. If it exercises the option, Huahui Anjian is entitled to an additional20millionupfrontpayment.Ifitexercisestheoption,HuahuiAnjianisentitledtoanadditional100 million option exercise fee. Upon achieving development and regulatory milestones, Huahui Anjian may receive up to 374 million. Upon achieving sales milestones, Huahui Anjian may receive up to374million.Uponachievingsalesmilestones,HuahuiAnjianmayreceiveupto1.53 billion, in addition to tiered royalties.

After monoclonal and bispecific antibodies have successively demonstrated their commercial value, expectations for BD in the trispecific space have rapidly risen. This track likely represents a new burst of China's "engineering" advantage in biopharmaceuticals.

Of course, whether trispecifics can truly transition from data to clinical reality will require more time and validation.

TONACEA 01: A Golden Target Combination Breakthrough

HH160 is a trispecific antibody developed using Huahui Anjian's proprietary PolyBoost platform, simultaneously targeting PD-1, CTLA-4, and VEGF-A—three "golden targets" in cancer therapy. This "triple-combo" design theoretically enables synergistic efficacy, tumor-specific drug distribution, and reduced treatment-related side effects.

Positive preclinical results for HH160 were presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting.

The popularity of the PD-1/VEGF target combination is largely attributable to the success of Akeso's PD-1/VEGF bispecific antibody ivonescimab (AK112). PD-1 awakens suppressed T cells, while VEGF improves the tumor microenvironment and promotes T cell infiltration into tumors, forming a complete immune activation loop. Adding CTLA-4 aims to further amplify T cell activation and proliferation during the priming phase, covering the entire process from activation to effector killing, with enhanced potential especially for "cold tumors" that respond poorly to traditional immunotherapy.

According to a Kaiyuan Securities analysis, as of August 8, 2025, there were 32 PD-(L)1 trispecific antibodies globally in clinical and preclinical development with active programs, of which 6 were PD-1/VEGF/CTLA-4 trispecifics in R&D. Three had entered Phase I clinical trials or beyond, all from China: Genor Biopharma's GB268, CStone Pharmaceuticals' CS2009, and MacroGenics' HC010.

In March 2026, CStone released the latest clinical data for CS2009. As of mid-March 2026, the Phase I trial had enrolled 113 patients with advanced solid tumors, with a median follow-up of approximately 6 months. The safety profile was notable: the incidence of grade ≥3 treatment-related adverse events was only 23%, with no severe toxicities commonly seen in CTLA-4 and PD-(L)1 combination regimens, and grade ≥3 VEGF-related adverse events were also rare.

In terms of efficacy, among first-line non-small cell lung cancer (NSCLC) patients with high PD-L1 expression (TPS ≥50%), CS2009 achieved an objective response rate (ORR) of 90% and a disease control rate (DCR) of 100%. Among immunotherapy-pretreated, actionable gene alteration (AGA)-negative second-line and later-line NSCLC patients, the ORR was 25%.

More notably, CS2009 also demonstrated potent anti-tumor activity against "cold tumors," achieving an ORR of 40% in non-clear cell renal cell carcinoma (nccRCC) patients and 33.3% in soft tissue sarcoma (STS) patients.

This data has quickly positioned CS2009 as the next potential BD pipeline from China.

TONACEA 02: Trispecifics Bloom Across the Board

Of course, the potential of trispecifics extends far beyond the classic PD-1/VEGF/CTLA-4 combination. Broadening the perspective reveals that global trispecific pipelines are showing increasing diversity in target combinations and molecular formats, with expanding therapeutic boundaries.

PD-(L)1-centric next-generation IO upgrades have become one of the mainstream paths for trispecific development. Beyond the popular CTLA-4 pairing, companies are also experimenting with combinations involving TGF-β, IL-2, and other targets, aiming to layer different mechanisms on top of immune suppression relief. This "PD-(L)1+X" approach fundamentally seeks even better synergy than bispecifics.

The diversification of target combinations is a surface phenomenon; deeper changes are occurring at the foundational capability level. Technological maturity has enabled novel molecular formats, rapidly moving them toward mainstream acceptance. Trispecific T-cell engagers (TCEs) are a representative example. Their core function is no longer simply relieving immune suppression but directly recruiting and activating T cells to kill tumors.

According to Yaozhi Data, as of April 2026, 32 TCE trispecifics had entered clinical trials globally, with two in Phase III: Johnson & Johnson's JNJ-79635322 and Zelgen Biopharmaceuticals/AbbVie's ZG006. China has become a major source of TCE trispecifics, accounting for 41% of those in clinical stages.

Source: Yaozhi Data

In late September 2025, Zelgen Biopharmaceuticals initiated a Phase III clinical study for ZG006 (targeting CD3/DLL3/DLL3) for relapsed small cell lung cancer (SCLC), making it the first tumor-targeting trispecific antibody globally to enter Phase III. Phase II data in 60 third-line or later SCLC patients showed confirmed ORRs of 53.3% and 56.7% in two dose groups, DCR of 73.3% for both, median PFS of 7.03 months and 5.59 months, respectively, with median OS data still immature. Both dose groups demonstrated good overall tolerability and safety, with no permanent discontinuations due to treatment-emergent adverse events (TEAEs). Common treatment-related adverse events (TRAEs) were pyrexia, cytokine release syndrome (CRS), and laboratory abnormalities, with the vast majority being Grade 1-2.

The evolution of technological pathways ultimately points to expanding clinical application scenarios. The ambition of trispecifics is no longer limited to oncology.

The battlefield for trispecifics has already extended to autoimmune diseases. In October 2024, GSK acquired CMG1A46 (CD19/CD20/TCE trispecific) from恩沐生物 for a 300 million upfront payment, targeting B-cell-driven autoimmune diseases such as systemic lupus erythematosus and lupus nephritis, with EnMu Bio additionally eligible for up to300millionupfrontpayment,targetingB−cell−drivenautoimmunediseasessuchassystemiclupuserythematosusandlupusnephritis,withEnMuBioadditionallyeligibleforupto550 million in milestones.

Sanofi is similarly positioning itself in the autoimmune trispecific space. In March 2026, Sanofi entered into a global exclusive license agreement with Kali Therapeutics, securing exclusive global rights to KT501. This deal included an 180 million upfront and near-term payment, with subsequent milestone payments potentially reaching180millionupfrontandnear−termpayment,withsubsequentmilestonepaymentspotentiallyreaching1.05 billion.

KT501 simultaneously targets CD3, CD19, and BCMA, covering multiple B-cell populations. Its unique CD3 masking platform maximizes potency while controlling cytokine release. These characteristics position KT501 as a promising candidate for treating B-cell-mediated autoimmune diseases.

These cases show that trispecific R&D is no longer confined to a single paradigm. From diversification of target combinations to evolution of molecular formats and expansion of indications, this "blooming across the board" R&D landscape provides a broader value foundation for the impending BD boom.

TONACEA 03: MNCs Rush In, Chinese New Drugs Break Through

Although trispecific development remains in early stages, BD deals have clearly heated up.

AbbVie has been one of the most aggressive buyers. In less than a year, AbbVie has completed three related transactions, with total deal value exceeding $4 billion.

In January 2025, AbbVie licensed SIM0500, a GPRC5D/BCMA/CD3 TCE trispecific from Simcere Zaiming. At the time, the drug was in Phase I clinical trials in both China and the U.S. The deal included option exercise payments and milestone payments up to $1.055 billion.

In July of the same year, AbbVie entered into a global collaboration with IGI Therapeutics for ISB-2001, a CD3/CD38/BCMA trispecific, with a total transaction value of 1.925 billion, including a1.925billion,includinga700 million upfront payment.

In December 2025, AbbVie moved again, partnering with Zelgen Biopharmaceuticals on ZG006, securing exclusive development and commercialization rights outside Greater China. Zelgen received a 100 million upfront payment and up to100millionupfrontpaymentandupto60 million in near-term milestones and option-related payments. If AbbVie exercises its option, Zelgen is eligible for an additional $1.075 billion in milestone payments, plus tiered royalties on net overseas sales.

It is evident that China remains the primary source of out-licensed trispecific assets. This clustering advantage makes it impossible for MNCs to ignore, especially as several high-value pipelines are approaching key data readouts, potentially sparking another wave of trispecific BD deals.

CStone Pharmaceuticals plans to initiate the first global multicenter Phase III trials for CS2009 by the end of 2026, focusing on NSCLC, colorectal cancer (CRC), SCLC, and other indications, with additional Phase I/II data expected to be presented at the 2026 ASCO or ESMO annual meetings.

Innovent Biologics presented first-in-human data for IBI3003 (GPRC5D/BCMA/CD3) in relapsed/refractory multiple myeloma at the 2025 ASH Annual Meeting, demonstrating a favorable safety profile and encouraging preliminary efficacy. IBI3003 showed promising results, particularly in high-risk patients with extramedullary disease or those previously treated with anti-BCMA and/or anti-GPRC5D single or dual targeted therapies. In January 2026, IBI3003 received Fast Track designation from the U.S. FDA.

Additionally, Henlius' tetra-specific antibody HLX3901 (DLL3/DLL3/CD3/CD28), developed from its proprietary TCE platform, received IND approval in March 2026 for SCLC and other neuroendocrine cancers. Akeso's first trispecific antibody, AK150 (LILRB1/LILRB2/CSF1R), also received clinical trial approval the same month, becoming the only globally developing trispecific targeting this combination.

On April 22, Sino Cell Tech registered a Phase II clinical trial for SCTB41 (PD-1/VEGF/TGF-β) plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced or metastatic NSCLC. Previously, SCTB41 had initiated a Phase I/II study for advanced solid tumors.

Currently, no trispecific antibody has been approved for marketing globally. Despite the R&D fervor, these drugs simultaneously target multiple antigens or immune cells, making them prone to inducing severe CRS, off-target toxicity, and immune-related adverse events (irAEs). Their complex molecular structures also present challenges in manufacturing, cost, and stability, requiring a careful balance between efficacy and safety in clinical development. While some leading pipelines have disclosed preliminary data, more clinical evidence is needed to fully address market concerns.

The BeiGene-Huahui Anjian transaction may be just the prelude to the coming wave of trispecific antibodies. Whether the trispecific space can truly deliver on the promise of "next-generation IO" will depend on clinical data and regulatory progress over the next two to three years. But at least one thing is already clear: after monoclonal and bispecific antibodies, China's innovative drug industry has once again positioned itself at the forefront of global competition in engineered antibodies.

References:

The Era of Multi-Specifics: R&D Foci, Target Portfolios, and Industry Opportunities for TCE Trispecifics; Bo Pharma

Can Trispecifics Replicate the "Myth" of Bispecifics? TONACEA

Sino Cell Tech: PD-1/VEGF/TGF-β Trispecific Initiates Phase II First-Line NSCLC Trial; Pharma Notes