Novel fusion protein shows potent macrophage activation, T-cell restoration, and tumor microenvironment remodeling in preclinical solid tumor models.
[Taipei, Shanghai, and San Francisco | November 5, 2025] –HanchorBio Inc. (TPEx: 7827), a global clinical-stage biotechnology company advancing next-generation immunotherapies for oncology and autoimmune diseases, today announced that the preclinical data on HCB301, a novel tri-specific immunotherapeutic fusion protein, has been accepted for presentation at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), taking place November 5-9, 2025, in National Harbor, Maryland. Featured in a poster presentation, the data highlight HCB301’s differentiated design and multi-pronged antitumor mechanism, which engages both innate and adaptive immunity.
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Focus on tumor treatment: block, activate, capture three arrows in flight
HCB301 is designed to simultaneously:
- Block SIRPα-CD47 interaction to re-initiate macrophage-mediated phagocytosis, and subsequent T-cell activation through antigen presentation.
- Block PD-1-PD-L1 signaling to restore exhausted T-cell function.
- Trap TGFβ to overcome stromal and immune suppression in the tumor microenvironment (TME).
This tripartite approach aims to overcome the limitations of existing checkpoint inhibitors by activating both arms of the immune system and triggering dual T-cell activation. It also further enhances T cell response by restoring its ability to target cancer cells in suppressive tumor microenvironments (TMEs), where current immune therapies often fail.
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HanchorBio Milestone of innovative immunotherapy
Scott Liu, Ph.D., Founder, Chairman, and CEO of HanchorBio, stated, “The tri-specific fusion protein of HCB301 is a showcase of the exceptional technological capabilities of HanchorBio, masterful in tackling the extremely difficult challenges in developing a structurally intricate fusion protein that includes two engineered receptors and a part (VHH domain) of an antibody. HCB301 was built directly on the foundation of HCB101, our clinical-stage SIRPα-engineered fusion protein.
By combining PD-1 blockade and TGFβ neutralization into a single molecule, HCB301 represents what we believe to be the first-in-class tri-specific fusion protein that simultaneously targets both innate and adaptive immune checkpoints and relieves immune suppression in TMEs characterized by suppressive cytokines. This design reflects our commitment to building modular, next-generation immunotherapies that may transcend the limitations of current cancer treatments.
With IND clearance and first-patient dosing now achieved in both the U.S. and China, HCB301 demonstrates the excellence and scalability of our FBDB™ platform and the outstanding execution capabilities of our research team. As we advance HCB301 into the clinic, this milestone further positions HanchorBio as a long-term innovation partner for global co-development, particularly in cancers with high resistance to traditional immunotherapies.”
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Preclinical Highlights of HCB301
HCB301, a tri-specific fusion protein targeting SIRPα/CD47, PD-1/PD-L1, and TGFβ, promotes anti-tumor macrophage and T cell activity in preclinical models of solid tumors
- Strong immune activation: HCB301 induced robust antibody-dependent cellular phagocytosis (ADCP), promoted macrophage-mediated phagocytosis, and activated effector T cells. It also activates T-cell response, leading to elevated secretions of IL-2 and IFN-γ.
- Synergistic antitumor efficacy: In Fadu (HNSCC)/PBMC Xenograft-bearing NPGTM mice and 4T1-hPDL1-hCD47 tumor-bearing BABL/c hPD1/hPDL1/hCD47/hSIRPα transgenic mice, HCB301 demonstrated superior tumor growth inhibition compared to single- or dual-arm comparators.
- TGFβ suppression: HCB301 potently neutralized active TGFβ (a dominant immune-suppressive cytokine), reversing TME immunosuppression and restoring T-cell function.
- Fc-effector tuning: Selective Fc engineering optimized immune activation while minimizing off-target toxicity.
“HCB301 was purpose-built to break through the resistance barriers that limit current PD-1 or CD47 monotherapies,” commented Wenwu Zhai, Ph.D., Chief Scientific Officer of HanchorBio. “Each of its three arms addresses a key axis of tumor immune evasion: CD47 for innate immune clearance, PD-1 for adaptive immune reactivation, and TGFβ for TME remodeling. Our preclinical data show that HCB301 delivers synergistic immune activation and tumor control, strongly supporting its advancement into the clinic.”
04 About HCB301
To our knowledge, HCB301 is the first clinical-stage tri-specific recombinant Fc-fusion protein that simultaneously targets SIRPα/CD47, PD-1/PD-L1, and TGFβ. It was designed using HanchorBio’s proprietary Fc-Based Designer Biologics (FBDB™) platform, which integrates modular, engineered multi-arm immunotherapies with tunable Fc regions and enhanced manufacturability.
HCB301 integrates:
- An engineered SIRPα domain that binds CD47 with much higher affinity (~100-fold higher than the wild-type SIRPα) to promote macrophage phagocytosis and subsequent T-cell activation.
- A PD-1 extracellular domain that blocks PD-L1 and restores T-cell effector function.
- A TGFβRII domain that traps active TGFβ molecules to alleviate immunosuppressive signals in the tumor microenvironment.
HCB301 shows a favorable safety profile in repeat-dose toxicology studies in cynomolgus monkeys. Its differential tumor vs. RBC binding profile may reduce the risk of anemia, thrombocytopenia, or other cytopenia while maintaining potent anti-tumor activity.
Following IND clearance and first-patient dosing in both the U.S. and China in 2025. The ongoing Phase 1 study (HCB301-101; NCT06487624) is a multi-regional, multi-center, open-label, dose-finding, first-in-human trial evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical efficacy of HCB301 in patients with advanced solid tumors or relapsed and refractory classical Hodgkin lymphoma.
About HanchorBio
Based in Taipei, Shanghai, and the San Francisco Bay Area, HanchorBio (TPEx: 7827) is a global biotechnology company specializing in immuno-oncology. It is led by an experienced team of pharmaceutical industry veterans with a proven track record in biologics discovery and international development, aiming to rewrite cancer therapies. Committed to reactivating the immune system to fight diseases, the proprietary Fc-based designer biologics (FBDB™) platform enables the development of unique biologics with diverse multi-targeting modalities, unleashing both innate and adaptive immunity to overcome the current challenges of anti-PD1/L1 therapies. The FBDB™ platform has successfully delivered proof-of-concept data in several in vivo tumor animal models. By making breakthroughs in multi-functional innovative molecular configurations in R&D and improving the manufacturing process in CMC, HanchorBio develops transformative medicines to address unmet medical needs.