CAMBRIDGE, Mass., ROTTERDAM, Netherlands and SUZHOU, China, May 28, 2023 /PRNewswire/ -- Harbour BioMed (the "Company", HKEX: 02142), a global biopharmaceutical company committed to the discovery, development, and commercialization of novel antibody therapeutics, today announced the results of phase Ib clinical trial of porustobart (HBM4003), in combination of toripalimab in patients with hepatocellular carcinoma (HCC) (trial code: NCT05149027) were released at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023.

Title: A Phase Ib Study of Porustobart (HBM4003), an anti-CTLA-4 Heavy Chain Only Monoclonal Antibody, in Combination with Toripalimab in Patients with Hepatocellular Carcinoma

Abstract Presentation Number: e16106

This is an open-label Phase Ib dose expansion study to evaluate the safety, tolerability, PK/PD and preliminary efficacy of HBM4003 in combination with toripalimab in patients with advanced HCC and other solid tumors.

Methods

Patients with advanced HCC (n=28) received porustobart 0.45 mg/kg plus toripalimab 240 mg every three weeks (Q3W) in both Cohort 1 and Cohort 2. Cohort 1 recruited patients who failed previous anti-VEGFR multikinase inh ibitor(s) treatment while have not received anti-PD-(L)1 treatment (n=16); Cohort 2 recruited patients who failed previous anti-PD-(L)1 and anti-VEGF(R) treatments (n=12). The primary endpoint was objective response rate (ORR) per RECIST 1.1.

Results

As of 9 December 2022, 28 patients had been dosed. The median follow-up time was 3.6 months.

• Porustobart in combination of toripalimab showed promising anti-tumor activity.

-  In Cohort 1, the ORR and disease control rate (DCR) were 46.7% and 73.3%, respectively in 15 patients with post-treatment tumor assessments.

-  In Cohort 2, the ORR and DCR were 9.1% (18.2% per mRECIST) and 54.5%, respectively in 11 patients with post-treatment tumor assessments.

• Porustobart in combination of toripalimab showed acceptable safety profile in HCC

-  Treatment-related adverse events (TRAEs) were reported in 89.3% (25/28) patients, and Grade 3 TRAEs were reported in 39.3% (11/28) patients. No Grade 4 or Grade 5 TRAE was reported.

• Porustobart in combination of toripalimab showed favorable PK/PD signature.

-  Porustobart promoted the clearance of Treg cells and the proliferation CD4⁺ and CD8⁺ T cell in periphery attested to its mechanism of action.

-  Greater effects were observed in Cohort 1, suggested a larger available pool of effectors to induce anti-tumor activity in the presence of effective Treg depletion.

-  No noticeable differences in PK between Cohort 1 and Cohort 2 were observed.

Conclusions

Porustobart 0.45 mg/kg plus toripalimab 240 mg Q3W showed promising anti-tumor activity and an acceptable safety profile in patients with advanced HCC.

Commenting on the study's results, Dr. Jingsong Wang, Founder, Chairman and Chief Executive Officer of Harbour BioMed, said, "We are excited to observe the promising efficacy and safety profile of porustobart and its potential to be developed as a cornerstone therapy in immuno-oncology. The continuous breakthrough in clinical studies of porustobart, the first molecule entered into clinical development generated from Harbour Mice^® HCAb, reflected superb innovation capabilities of our team and vast  value of our industry leading technology platforms. We are fully committed to advancing the clinical development project of porustobart to address the significant unmet medical needs in multiple solid tumor indications."

About Porustobart 

Porustobart is a fully human anti-CTLA-4 monoclonal heavy chain only antibody (HCAb) generated from Harbour Mice^®. By enhancing antibody-dependent cell cytotoxicity (ADCC) killing activity, porustobart has demonstrated significantly improved depletion specific to high CTLA-4 Treg cells in tumor tissues. The potent anti-tumor efficacy and differentiated pharmacokinetics with durable pharmacodynamic effect presents 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 combo-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 heavy chain only (HCAb) format. Building upon the HCAb antibodies, the HCAb-based immune cell engagers (HBICE^®) are capable of delivering tumor killing effects unachievable by traditional combination therapies. Integrating Harbour Mice^® with single B cell cloning platform, our antibody discovery engine is highly unique and efficient for development of next generation therapeutic antibodies.

SOURCE Harbour BioMed