Harbour BioMed will present Phase II clinical data on its next-generation anti-CTLA-4 antibody porustobart (HBM4003) in combination with tislelizumab for the treatment of microsatellite stable (MSS) metastatic colorectal cancer at the ESMO Congress 2025, taking place October 17-21, 2025, in Berlin, Germany.
The presentation addresses a significant unmet medical need, as MSS mCRC remains a therapeutic challenge with limited response to immune checkpoint inhibitors. The multicenter, open-label Phase II study (NCT05167071) enrolled heavily pretreated non-liver metastatic MSS mCRC patients, with preliminary efficacy and safety data to be presented in poster session 807P by speaker Frank Zheng.
Novel Antibody Technology Platform
Porustobart represents a breakthrough in CTLA-4 targeting, being the first fully human heavy-chain-only antibody to enter clinical development globally. The antibody was discovered and developed using Harbour BioMed's proprietary HCAb Harbour Mice® platform, which generates fully human monoclonal antibodies in both conventional two heavy and two light chain (H2L2) format and the heavy chain-only (HCAb) format.
Compared with conventional CTLA-4 antibodies, porustobart demonstrates unique, favorable properties including significant Treg cell depletion and optimized pharmacokinetics for improved safety. The antibody enhances antibody-dependent cellular cytotoxicity (ADCC), increasing the potential to selectively deplete intratumoral Treg cells and helping to overcome the efficacy and toxicity bottleneck of current CTLA-4 therapies.
Preclinical Evidence and Clinical Development
Preclinical evidence supports the synergistic antitumor activity of CTLA-4 blockade combined with PD-(L)1 inhibition in mouse models. Harbour BioMed has implemented a global development plan for multiple types of solid tumors with an adaptive treatment design for porustobart.
Positive efficacy and safety data have been observed in monotherapy trials targeting advanced solid tumors, as well as in combination trials with PD-1 inhibitors for melanoma, colorectal cancer, neuroendocrine neoplasms, and hepatocellular carcinoma.
Comprehensive Technology Platform
Harbour BioMed's antibody discovery capabilities extend beyond conventional approaches through its integrated platform. Building upon HCAb antibodies, the company's HCAb-based immune cell engagers (HBICE®) bispecific antibody technology enables tumor-killing effects that traditional combination therapies cannot achieve. Additionally, the HCAb-based bispecific immune cell antagonist (HBICA™) technology empowers the development of innovative biologics for immunological and inflammatory diseases.
By integrating Harbour Mice®, HBICE®, and HBICA™ with a single B-cell cloning platform, Harbour BioMed has built a highly efficient and distinctive antibody discovery engine for developing next-generation therapeutic antibodies. The company continues to build a robust and differentiated pipeline through internal R&D capabilities, strategic global collaborations in co-discovery and co-development, and selective acquisitions.
