Late-breaking poster presentations show HCB101’s favorable safety, strong receptor occupancy, and promising monotherapy and combination activity in tumors historically unresponsive to immunotherapy
TAIPEI, SHANGHAI, and SAN FRANCISCO, Nov. 7, 2025 /PRNewswire/ — HanchorBio Inc. (TPEx: 7827), a global clinical-stage biotechnology company advancing next-generation immunotherapies for oncology and autoimmune diseases, today announced the presentation of two late-breaking abstracts on its lead asset, HCB101, at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), held November 5-9, 2025, in National Harbor, Maryland. Both datasets were accepted for late-breaking poster presentations, highlighting the program’s potential impact on innate immune checkpoint blockade.
HCB101’s progress reflects its distinct engineering compared to earlier CD47-targeting approaches. First-generation CD47 antibodies, such as magrolimab and lemzoparlimab, demonstrated clinical activity but faced significant safety or efficacy challenges, leading to discontinuations or halted collaborations. Second-generation wild-type SIRPα fusions, such as maplirpacept (TTI-622), improved safety but did not deliver sufficient efficacy in solid tumors, limiting their adoption. IgG1-based fusions attempted to boost immune activation but triggered excessive Fcγ-mediated toxicity and poor tolerability, restricting their use mainly to hematologic malignancies. Third-generation engineered SIRPα fusions with inactivated IgG1 Fc improved safety in combinations but showed limited standalone efficacy.
“The acceptance of two late-breaking abstracts at SITC for HCB101 monotherapy and combination therapy, along with our earlier preclinical abstract for HCB301, a tri-specific fusion targeting SIRPα/CD47, PD-1/PD-L1, and TGFβ, reinforces the scientific breadth of our platform across innate and adaptive immunity,” said Scott Liu, Ph.D., Founder, Chairman, and CEO of HanchorBio. “HCB101 was purposely engineered to overcome the cytopenias seen with first-generation anti-CD47 antibodies while maintaining potent immune activation. In second-line gastric cancer, the combination of HCB101 with standard-of-care therapy achieved a 100% confirmed response rate in the active-dose cohort, far exceeding the 28% ORR benchmark from the RAINBOW trial. These results position HCB101 not just as a safer SIRPα-CD47 backbone, but as a next-generation macrophage checkpoint immunotherapy with best-in-class potential.”
Late-Breaking Abstract Highlights (Data as of August 2025)
1. HCB101-101 Monotherapy Study (NCT05892718)
Title: HCB101, a Next-Generation Fc-Engineered SIRPα-CD47 Fusion Protein, Demonstrates Favorable Safety and Early Antitumor Activity in Advanced Cancers
- In the ongoing Phase 1a dose-escalation, no dose-limiting toxicities (DLTs) have been observed at doses up to 24 mg/kg.
- CD47 receptor occupancy ≥99% achieved at doses ≥5 mg/kg, with dose-proportional pharmacokinetics.
- Confirmed partial responses seen in head and neck squamous cell carcinoma (HNSCC) and marginal zone lymphoma (MZL).
- Several patients achieved stable disease, with progression-free survival up to 32 weeks.
2. HCB101-201 Combination Therapy Study (NCT06771622)
Title: Phase 1b/2a Study of HCB101 Combined with Standard Therapies Demonstrates Manageable Safety and Dose-Dependent Antitumor Activity in Immunologically Cold Advanced Solid Tumors
- In second-line gastric cancer (GC):
- 100% confirmed partial response rate (6/6 evaluable patients) at active doses when combined with ramucirumab and paclitaxel.
- Tumor shrinkage up to 78%, surpassing the ~26.5% ORR benchmark from RAINBOW.
- In first-line triple-negative breast cancer (TNBC):
- Confirmed partial response with 73% tumor reduction at the effective dose.
- Safety was manageable and consistent with the cytopenia-sparing design, with only minimal hematologic effects observed.
Dr. Fangling Ning, Investigator from the Affiliated Hospital of Binzhou Medical University, commented, “What’s unique about HCB101 is that it avoids the cytopenias that plagued anti-CD47 antibodies by minimizing red blood cell binding, while still engaging CD47 strongly on tumor cells. In our gastric cancer cohort, the responses at active doses are encouraging in a patient population that historically has had limited options. These findings validate HCB101’s unique design and suggest meaningful potential in immunologically cold tumors.”
About HCB101: A Differentiated CD47-SIRPα Blockade
HCB101 is a 3.5th-generation, affinity-optimized SIRPα-Fc fusion protein with an intact IgG4 Fc backbone, developed using HanchorBio’s proprietary FBDB™ platform. It is engineered for selective CD47 targeting with low red blood cell (RBC) binding, thereby avoiding the anemia and thrombocytopenia commonly associated with earlier anti-CD47 monoclonal antibodies, while preserving strong antibody-dependent cellular phagocytosis (ADCP) and innate-to-adaptive immune bridging. Key differentiators of HCB101:
- Enhanced safety: Cytopenia-sparing profile, with no DLTs observed up to 30 mg/kg and receptor occupancy >90% at ≥1.28 mg/kg, supporting a broad therapeutic window.
- Robust immune activation: Engineered to enhance ADCP and bridge innate-to-adaptive immunity, with evidence of durable immune-mediated tumor control in monotherapy.
- Broad tumor applicability: Demonstrated activity across >80 PDX and CDX preclinical models, with early clinical signals in gastric cancer, TNBC, HNSCC, non-Hodgkin lymphoma, and ovarian cancer.
- Clinical translation: Shows durable disease control as monotherapy and a 100% confirmed partial response rate (6/6) in 2L gastric cancer when combined with ramucirumab and paclitaxel, with additional confirmed responses in 1L TNBC and 2L HNSCC, substantially exceeding historical benchmarks.
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 the landscape of 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 advancing breakthroughs in multi-functional, innovative molecular configurations in R&D and improving CMC manufacturing processes, HanchorBio develops transformative medicines to address unmet medical needs. For more information, please visit: https://www.hanchorbio.com
SOURCE HanchorBio Inc.
