HanchorBio’s SIRPα fusion protein takes FDA orphan status in gastric cancer

HanchorBio, Inc. (TPEx: 7827), a clinical-stage biotechnology company headquartered in Taipei, Shanghai, and San Francisco, announced that the US FDA has granted Orphan Drug Designation (ODD) to HCB101 for the treatment of gastric cancer. The designation encompasses advanced gastric adenocarcinoma in both HER2-positive and HER2-negative subtypes.

HCB101 is a SIRPα-IgG4 Fc fusion protein engineered to block the CD47–SIRPα innate immune checkpoint, a pathway that tumors exploit to evade macrophage-mediated phagocytosis. According to the company, HCB101 is the first molecule of this modality to receive orphan status in gastric cancer.

The designation provides HanchorBio with a package of regulatory incentives codified under the Orphan Drug Act. These include eligibility for tax credits on qualified clinical trial expenditures conducted in the United States, exemption from Prescription Drug User Fee Act (PDUFA) filing fees, and the potential for seven years of market exclusivity following approval in the orphan indication.

Gastric cancer qualifies as a rare disease in the United States, with prevalence below the statutory threshold of 200,000 affected individuals that the FDA uses to determine orphan eligibility. The disease remains a leading cause of cancer mortality globally, and outcomes in the second-line setting — where patients have progressed on initial platinum and fluoropyrimidine-based chemotherapy — are poor. Median overall survival on standard second-line regimens remains limited, and durable responses are uncommon.

HanchorBio’s development platform

HCB101 was developed internally by HanchorBio on the company’s proprietary FBDB (Fc-Based Designer Biologics) platform, which is designed to generate multi-functional biologics capable of engaging both innate and adaptive immune pathways. The molecule was engineered using AI-assisted structural modeling to achieve differentiated binding characteristics: high affinity for CD47 expressed on tumor cells, and low affinity for CD47 on red blood cells. This design choice addresses the central pharmacologic liability that has constrained earlier CD47-targeting programs, namely on-target, off-tumor hematologic toxicity manifesting as anemia and thrombocytopenia.

HCB101 is currently being evaluated in a Phase Ib/IIa combination study — NCT06771622. The trial is listed as active with an enrollment target of 500 patients, a start date of March 2025, and an estimated primary completion date of January 2028. HanchorBio has also disclosed a specific cohort evaluating HCB101 in combination with ramucirumab and paclitaxel in second-line advanced gastric cancer.

The CD47–SIRPα pathway

The competitive landscape surrounding HCB101 gastric cancer development is defined less by direct competitors in the same indication and more by the broader trajectory of CD47-directed therapeutics, a field that has experienced a series of clinical failures that have reshaped how developers approach the target.

The most consequential setback was the termination in 2024 of Gilead Sciences’ Phase III programs for magrolimab, an anti-CD47 monoclonal antibody, in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The ENHANCE-2 and ENHANCE-3 trials were discontinued after futility analyses, compounded by safety signals including increased infection-related mortality.

ALX Oncology’s evorpacept (ALX148), a SIRPα-Fc fusion protein that shares a conceptual lineage with HCB101 as a decoy receptor approach rather than a direct anti-CD47 antibody, also encountered difficulty. The ASPEN-06 Phase II/III trial in head and neck squamous cell carcinoma did not meet its primary endpoint.

Several programs remain active. Akesobio’s AK117, an anti-CD47 antibody engineered to reduce red blood cell binding, is in Phase II/III trials in hematologic malignancies. Chia Tai Tianqing’s TQB2928 is similarly in Phase II/III. Innovent Biologics maintains two CD47-related programs: letaplimab (IBI188), an anti-CD47 antibody in Phase II, and IBI322, a CD47 × PD-L1 bispecific antibody in Phase I/II designed to restrict CD47 blockade to PD-L1-expressing tumor cells. ImmuneOnco’s IMM0306 (CD47 × CD20 bispecific) and IMM2902 (CD47 × HER2 bispecific) represent further iterations on the tumor-directed bispecific strategy. Pfizer’s TTI-621 and TTI-622, SIRPα-Fc fusions acquired from Trillium Therapeutics, remain in Phase I/II evaluation.

HCB101’s design as an affinity-optimized SIRPα-IgG4 Fc fusion protein, rather than a direct anti-CD47 antibody, places it as a next-generation molecule, engineered to maintain low affinity for erythrocyte-expressed CD47. Unlike evorpacept, which used a wild-type SIRPα domain fused to an IgG1 Fc, HCB101 employs an IgG4 Fc backbone — a choice that may reduce Fc-mediated effector functions against normal cells while preserving the phagocytic signaling required for antitumor activity.