On June 1, 2022 Harbour BioMed (the "Company", HKEX: 02142), a global biopharmaceutical company committed to the discovery, development, and commercialization of novel antibody therapeutics, reported the progress of its dual MOA of CTLA-4 inhibition and Treg depletion, next-generation fully human heavy-chain antibody (HBM4003) with studies of monotherapy and combination therapy with anti-PD-1 antibody (Press release, Harbour BioMed, JUN 1, 2022, View Source [SID1234615385]). The two abstracts have been published on the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) website and will be presented at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting.

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Abstract One:

Study title: A Phase I Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of HBM4003 in Subjects with Advanced Solid Tumors

Abstract number: 2641

Poster number: 296

This is an open-label, multi-center study on subjects with solid tumors to receive HBM4003 at dose levels (DLs) of 0.3mg/kg QW (28-day cycle), 0.45mg/kg Q3W (21-day cycle), and 0.6mg/kg Q3W (21-day cycle). In the dose-expansion part, patients with advanced hepatocellular carcinoma (HCC), melanoma, and renal cell carcinoma (RCC) received 0.45 mg/kg Q3W (21-day cycle).
24 patients with advanced solid tumors in the dose-escalation part and 36 patients in the dose-expansion part, from 12 sites in mainland China, 5 sites in Australia, and 1 site in Hong Kong, China; including 19 HCC patients and 19 RCC patients. 46 patients (77%) received ≥ 2 lines of previous systemic therapies and 37 patients (62%) received previous PD-1/PD-L1 treatment.
In the HCC cohort, all 19 patients received previous PD-1/PD-L1 therapy, and 12 patients were evaluable for efficacy. 2 patients had stable disease (SD) and 2 patients had partial response (PR) as the best response. The objective response rate (ORR) was 16.7% and the disease control rate (DCR) was 33.3%.
Among the 19 RCC patients, 18 patients were evaluable for efficacy. 8 patients had SD as the best response; the DCR was 44.4%.
Overall, the most common treatment-related adverse event (TRAE) of all grades was rash (16 [26.7%] patients). At the 0.45 mg/kg Q3W DL, Grade≥3 TRAEs occurred in 4 (9.3%) patients, 1 patient reported Grade 4 TRAE, and no Grade 5 TRAE was reported.
The recommended phase II dose was selected as 0.45mg/kg Q3W.
Sustained Treg depletion was observed in tumor tissue on day 21 post dosing.
Abstract Two

Study title: A Phase I Open-label Study to Evaluate the Safety, Tolerability, PK/PD and Anti-tumor Activity of HBM4003 in Subjects with Advanced Melanoma and Other Solid Tumors

Abstract number: e14586

This is a phase I study to evaluate the safety, anti-tumor activity, PK/PD, and recommended phase II dose of HBM4003 in combination with toripalimab. In dose-escalation part, patients were enrolled to receive HBM4003 at 3 dose levels (DLs) (0.03 mg/kg Q3W, 0.1 mg/kg Q3W, and 0.3 mg/kg Q3W) combined with toripalimab 240 mg. In dose-expansion part, patients with advanced melanoma will be treated at recommended phase II dose.
As of 30 November 2021, in total 11 patients have been treated at one site in China, including 9 with melanoma, 1 with renal cell carcinoma, and 1 with urothelial carcinoma. 4 patients received ≥ 2 lines of previous systemic therapies and 8 received previous PD-1/PD-L1 treatment.
The most common TRAE of all grades was leukopenia (4 [36.4%] patients), followed by lymphopenia (3 [27.3%] patients). No > Grade 3 TRAE reported.
At the 0.3mg/kg Q3W DL, 6 patients were evaluable for efficacy: 2 patients had SD as the best response, whereas 1 patient had PR as the best response (mucosal melanoma, 2 lines of previous treatment including toripalimab), with tumor shrinkage of 32.6% (Week 12).
HBM4003 0.3mg/kg Q3W in combination with toripalimab showed promising antitumor activity and a tolerable safety profile in advanced melanoma and other solid tumors. Hence, 0.3mg/kg Q3W was selected as the recommended dose for dose-expansion in advanced melanoma.
Particularly in the study of HBM4003 in combination with toripalimab, another PR from a urothelial carcinoma patient (3 lines of previous treatments including toripalimab) was observed at the end of 2021. As of the date of issue, the patient recruitment of the dose-expansion part in this study has been completed.

Commenting on the studies’ results, Dr. Humphrey Gardner, CMO of Harbour BioMed, said, "we are excited to observe the promising efficacy and excellent safety profile of HBM4003 and its potential to lead the development of next-generation therapy of immuno-oncology for multiple solid tumors. The Treg depleting activity of HBM4003 offers a potential for clinical efficacy in indications hitherto unaddressed by first generation CTLA4 inhibitors. The clinical results obtained so far have given us the confidence for further global development of HBM4003, and further relevant study results will be published in the upcoming academic conferences."

As the Company further implements its global innovation and development strategy, it will continue to fully commit to advancing the global clinical development project of HBM4003, as part of its broad and innovative immuno-oncology pipeline to address the significant unmet medical needs in multiple solid tumor indications.

About HBM4003

HBM4003 is a fully human anti-CTLA-4 monoclonal heavy chain only antibody (HCAb) generated from Harbour Mice. It is the first fully human heavy-chain-only monoclonal antibody entered into clinical stage globally. By enhancing antibody-dependent cell cytotoxicity (ADCC) killing activity, HBM4003 has demonstrated significantly improved depletion specific to high CTLA-4 expressing 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 combination therapy.