BeOne Medicines secures exclusive option to Huahui's preclinical trispecifics in up-to-$2B deal

On April 27, BeOne Medicines issued an announcement that its wholly‑owned subsidiary, BeOne Medicines Guangzhou, entered into a Collaboration Agreement with Huahui Health on April 24. Under this Agreement, Huahui Health grants BeOne Medicines Guangzhou an exclusive option, upon exercise of which BeOne Medicines Guangzhou may obtain an exclusive license to develop, manufacture, and commercialize, on a worldwide basis and for all uses, Huahui Health's investigational trispecific compounds targeting PD-1, CTLA-4, and VEGF‑A (including HH160) and any products containing such compounds.

The total consideration under this transaction is up to USD 2.024 billion, with the following payment structure: a USD 20 million upfront payment; if BeOne Medicines Guangzhou exercises the option within the specified period, an additional option exercise payment of USD 100 million; upon achievement of development and regulatory milestones, Huahui Health may receive payments of up to USD 374 million; and upon achievement of sales milestones, Huahui Health may receive payments of up to USD 1.53 billion, together with tiered royalties.

The core asset of this transaction is a trispecific compound targeting PD-1, CTLA-4, and VEGF-A, including HH160.

HH160 is a hexavalent trispecific antibody developed by Huahui Health based on its proprietary PolyBoost™ multispecific antibody platform. Constructed on a bevacizumab backbone, the molecular structure incorporates Fc-silencing modifications that eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC), thereby reducing immune-related inflammatory responses.

In terms of mechanism of action, HH160 simultaneously targets three clinically well-validated oncology therapeutic targets: PD-1 blockade reverses T cell exhaustion and restores T cell antitumor activity; CTLA-4 blockade promotes T cell activation and proliferation, enhancing immune responses; and VEGF-A neutralization inhibits tumor angiogenesis, improves the tumor microenvironment, and increases the efficiency of immune cell infiltration.

Compared with other trispecific antibody molecules of the same class, HH160 possesses a unique and differentiating mechanism. It mediates CTLA-4-dependent VEGF-A internalization, efficiently depleting VEGF-A in the tumor microenvironment and breaking the vicious cycle of tumor angiogenesis and immunosuppression. Preclinical data related to this mechanism have been presented as a poster at the 2025 AACR Annual Meeting.

Currently, HH160 is at the preclinical stage. An Investigational New Drug (IND) application has not yet been submitted, and no human clinical trials have been conducted.

Preclinical studies have shown that, in human peripheral blood mononuclear cell-derived macrophage assays, HH160 induces lower levels of IL-6 and IL-8 compared to the PD-1/CTLA-4 bispecific antibody AK104, the PD-1/VEGF bispecific antibody AK112, and other trispecific antibodies of the same class such as HC010, suggesting a potential reduction in the risk of immune-related adverse events (irAEs). Additionally, HH160 demonstrates significantly higher binding affinity for PD-1/CTLA-4 double-positive cells than AK112, and its PD-1/CTLA-4 functional blocking activity is superior to the simple combination of PD-1 and CTLA-4 monoclonal antibodies as well as other bispecific antibodies of the same class.

On the foundation of steady volume growth of core products such as zanubrutinib and tislelizumab, BeOne Medicines is also rapidly strengthening its next-generation immuno-oncology pipeline through business development via licensing deals, transitioning from monoclonal antibodies to bispecific and then to trispecific antibodies, and perfecting its complete landscape spanning hematologic malignancies to solid tumors, and from immune checkpoints to tumor microenvironment modulation.

The introduction of HH160 in this transaction serves both as a pipeline supplement to tislelizumab and as a strategic move to secure a leading position in the post-PD-1 era of immunotherapy. Leveraging BeOne Medicines' global clinical development and commercialization network, this preclinical trispecific antibody can be rapidly advanced from IND submission to pivotal clinical trials, with the potential to address unmet needs such as PD-1 resistance and cold tumors.

From a competitive landscape perspective, no product targeting the PD-1/CTLA-4/VEGF-A trispecific axis has been approved to date, and a clear hierarchical differentiation in industrial development has emerged.

CStone Pharmaceuticals' CS2009 is the most advanced, currently in global multi-center Phase I/II clinical trials with an FDA IND already approved, demonstrating promising efficacy and safety in indications including non-small cell lung cancer (NSCLC). Genor Biopharma's GB268 and HC Pharmaceutical's HC010 are both in Phase I clinical trials, employing designs that attenuate peripheral CTLA-4 affinity to control toxicity, representing a clear mechanistic differentiation from HH160, which features high-affinity CTLA-4 combined with Fc-silencing design. This transaction validates the value of the trispecific antibody space; however, structural design, toxicity control, and clinical data of different molecules will ultimately be the core determinants of success.

At the industry development level, cancer immunotherapy has entered the 3.0 era, advancing from monoclonal and bispecific antibodies to trispecific antibodies. The PD-1/VEGF/CTLA-4 target combination, which simultaneously covers immune activation and tumor microenvironment modulation, has become a prominent focus area for research and development and licensing activities.

Compared with combination therapy using bispecific antibodies, a single trispecific molecule enables multi-target synergistic effects, reduces treatment costs, simplifies dosing regimens, and minimizes the cumulative toxicity risk associated with polypharmacy. However, the technical barriers in molecular design, manufacturing processes, and clinical translation are significantly higher, imposing greater demands on companies' research and development capabilities and clinical execution. Currently, local Chinese companies hold a leading global position in this space. In addition to the aforementioned companies, Akeso, Innovent Biologics, and Hengrui Medicine have all built bispecific and trispecific pipelines, driving the transformation of local innovative drugs from followers to leaders.

From an industry trend perspective, the trispecific antibody space will gradually enter a stage where clinical data become the battleground. The scientific validity of molecular design, the balance between efficacy and safety, and the efficiency of clinical translation will be core competitive factors. Meanwhile, as competition in the PD-1 monoclonal antibody space intensifies, next-generation immunotherapies such as bispecific and trispecific antibodies have become key for companies to break out of homogeneous competition and capture market share. It is expected that over the next one to three years, more trispecific antibody molecules will advance to later-stage clinical development, with industry concentration expected to increase gradually.