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PNAS Published Preclinical Results of Harbour BioMed’s Next-Generation Fully Human Heavy-chain Antibody Porustobart

August 08, 2022

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PNAS Published Preclinical Results of Harbour BioMed’s Next-Generation Fully Human Heavy-chain Antibody Porustobart

August 08, 2022

Cambridge, MA, Rotterdam, NL, Suzhou, CN— Aug 8, 2022


Harbour BioMed (the “Company”, HKEX: 02142) announced that the preclinical results of porustobart (HBM4003), a next-generation fully human heavy-chain antibody with a Treg depletion mechanism, were published in the Proceedings of the National Academy of Sciences (PNAS). For the last two years, HBM scientists have published paper on top tier journals such as Nature Communications, Science Immunology, and now PNAS.


Porustobart (HBM4003), with a unique molecular structure shows an excellent preclinical efficacy and safety profile:


1. A fully human heavy-chain antibody (HCAb), HBM4003 binds human CTLA4 with high affinity reaching 10-11 M.

2. It effectively depletes tumor-resident Treg with enhanced antibody-dependent cellular cytotoxicity (ADCC).

HCAb 4003-2 showed, maximally, 60% lysis of in vitro differentiated Treg cells at 1 nMol concentration. The median effective concentration of HCAb 4003-2 was about 100-fold more potent than the current standard antibody.


3. It shows potent tumor penetration due to its small size, resulting in a more widely effect on T cell activation.

Mice were dosed with labeled HCAb 4003-2 or hIgG1. Peak signal was detected at 1h in normal tissues, while it was maximal at 24h in the tumor, showing superior tumor penetration for HCAb4003-2 than hIgG1.


4. Less systemic drug exposure in vivo potentially provides an improved therapeutic window in clinical applications.

In MC38-bearing human CT LA-4 knock-in (KI) C57BL/6 mice and CT26-bearing huCTLA-4 KI Balb/c mice, 4003 showed higher potency than the standard anti CTLA4 antibody.

More importantly, 4003 showed an excellent safety profile. A single dose of 4003-2 at 30 mg/kg was well tolerated in cynomolgus monkeys.


About PNAS


PNAS is one of the world's most-cited and comprehensive multidisciplinary scientific journals. The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), is an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.


About Porustobart (HBM4003)


Porustobart (HBM4003) is a fully human anti-CTLA-4 heavy chain antibody (HCAb) generated in Harbour Mice®. It is the first fully human heavy chain antibody entered into clinical stage globally. By enhancing antibody-dependent cell cytotoxicity (ADCC) killing activity, porustobart demonstrates significantly improved depletion of high CTLA-4 expressing Treg cells in tumor tissues. The potent anti-tumor efficacy and differentiated pharmacokinetics with durable pharmacodynamic effect present a favorable product profile. This novel and differentiated mechanism of action has the potential to improve efficacy while significantly reducing the toxicity of the drug in monotherapy and combination therapy.


About Harbour BioMed


Harbour BioMed (HKEX: 02142) is a global biopharmaceutical company committed to the discovery, development and commercialization of novel antibody therapeutics focusing on immunology and oncology. The Company is building its robust portfolio and differentiated pipeline through internal R&D capability, collaborations with co-discovery and co-development partners and select acquisitions.
The Company’s proprietary antibody technology platforms, Harbour Mice® generate fully human monoclonal antibodies in two heavy and two light chain (H2L2) format, as well as two heavy chain only (HCAb) format. Building upon the HCAb antibodies, the HCAb-based immune cell engagers (HBICE®) bispecific antibody technology is capable of delivering tumor killing effects unachievable by traditional combination therapies. Integrating Harbour Mice®, HBICE® with single B cell cloning platform, our antibody discovery engine is highly unique and efficient for development of next generation therapeutic antibodies.  

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Harbour BioMed Public Relations