Harbour BioMed Announces Results of Phase Ib Clinical Trial of Porustobart in Combination with Toripalimab in Advanced High-Grade Neuroendocrine Neoplasms at AACR Annual Meeting

• Porustobart in combination with toripalimab showed promising anti-tumor activity in advanced high-grade neuroendocrine neoplasms (NENs)
• The ORR and DCR were 38.5% and 69.2% in neuroendocrine carcinoma (NEC) patients
• The results showed great potential to develop porustobart as a cornerstone therapy for immuno-oncology.

CAMBRIDGE, Mass., ROTTERDAM, Netherlands and SUZHOU, China, April 14, 2023 /PRNewswire/ -- Harbour BioMed (“HBM”, HKEX: 02142), a global biopharmaceutical company committed to the discovery, development, and commercialization of novel antibody therapeutics focusing on immuno-oncology and immunology, today announced that the results of its phase Ib clinical trial of porustobart (HBM4003) in combination of toripalimab in patients with advanced high-grade neuroendocrine neoplasms (NENs) (trial code: NCT05167071) had been scheduled for presentation in a poster session at the American Association for Cancer Research (AACR) Annual Meeting 2023 and published in the online proceedings of the AACR.

This is an open label phase Ib clinical study to evaluate the safety, tolerability, PK/PD and preliminary efficacy of porustobart combined with toripalimab in patients with advanced NEN and other solid tumors.

Details and highlights:

Title: A phase Ib dose-expansion study of porustobart, an anti-CTLA-4 heavy chain only monoclonal antibody, in combination with toripalimab in patients with advanced high-grade NENs

Location: Poster Section 47
Poster Board Number: 3
Abstract Presentation Number: CT263

Methods:

Patients (pts) with pretreated advanced high-grade NENs received porustobart at one of the two dose levels (0.3 mg/kg and 0.45 mg/kg) plus toripalimab 240 mg every three weeks (Q3W). The primary endpoint is objective response rate (ORR) per RECIST 1.1 by investigator.

Results:

As of 9 November 2022, 21 pts had been dosed. The median follow-up time was 5.9 months for 0.3 mg/kg dose group and 2.8 months for 0.45 mg/kg dose group, respectively.

• Porustobart in combination with toripalimab showed promising anti-tumor activity in advanced high-grade NENs. No significant difference in efficacy was observed between the two dose groups.
  • The overall ORR and DCR (disease control rate) were 38.9% and 61.1%, respectively, and the 3-month DOR (duration of response) rate was 80%, while the median DOR was not reached.
  • For patients with NEC (neuroendocrine carcinoma), the ORR and DCR were 38.5% and 69.2%, respectively.

• Porustobart in combination with toripalimab showed acceptable safety profile.
  • Treatment-related adverse events (TRAEs) were reported in 100.0% (21/21) patients, and ≥Grade 3 TRAEs were reported in 33.3% (7/21) patients. The most common (≥20%) TRAEs were hepatic function abnormal, hyperthyroidism, rash, leukopenia, anaemia, pyrexia, neutrophil count decreased, hypothyroidism and thrombocytopenia.

• Porustobart in combination with toripalimab showed unique PK/PD signature.
  • PK data indicated no potential interaction between porustobart and toripalimab.
  • Porustobart promoted Treg reduction and CD4⁺ and CD8⁺ T cell proliferation in periphery attested to its mechanism of action.

Conclusions

Porustobart 0.3 mg/kg or 0.45 mg/kg plus toripalimab 240mg Q3W showed promising anti-tumor activity and an acceptable safety profile in pts with advanced high-grade NENs.

The above results demonstrated robust clinical response rate in difficult-to-treat high-grade NENs that were generally not sensitive to current therapies. The results showed great potential to develop porustobart as a cornerstone therapy in immuno-oncology. The Company is also conducting other clinical studies of combination therapy for other advanced solid tumors, such as hepatocellular carcinoma and melanoma.

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.

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SOURCE Harbour BioMed