News | December 13, 2023

First Subject Dosed For Phase 1 Clinical Trial Of Henlius' Ipilimumab Biosimilar HLX13

Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first subject was dosed for a phase 1 clinical trial of the company's independently developed ipilimumab biosimilar HLX13 (recombinant anti-CTLA-4 fully human monoclonal antibody injection) in China.

Immune checkpoint inhibitors are playing a crucial part in immunotherapy, which has emerged in recent years as a novel approach to combating tumour cells with distinct advantages and enormous promise [1]. In addition to PD-1/L1 and LAG-3, CTLA-4 is also an inhibitory immune checkpoint which expressed on regulatory T cells and activated T cells and has a higher affinity to B7 molecules compared with CD28, thus can competitively bind to B7 molecules to inhibit the proliferation and activation of T cells [2]. Anti-CTLA-4 fully human monoclonal antibody (mAb) can block the inhibitory effects of CTLA-4 on the co-stimulation signal necessary to T cell activation and can increase the number of reactive T-effector cells which mobilize to mount a direct T-cell immune attack against tumour cells. Also, anti-CTLA-4 mAb may selectively deplete T-regulatory cells at the tumour site, leading to an increase in the intratumoral T-effector/T-regulatory cell ratio which drives tumour cell death. Meanwhile, results showed that the combination therapy of anti-CTLA-4 mAb and anti-PD-1 mAb is expected to have a synergistic effect and may bring additional clinical benefit to patients [3-4].

HLX13 is a biosimilar of ipilimumab independently developed by Henlius in accordance with the NMPA, EMA, FDA and other international biosimilar guidelines. The indications to be developed for HLX13 are solid tumours. Henlius has conducted a series of head-to-head pre-clinical studies to compare the chemical manufacture and control (CMC), pharmacology, toxicity, and pharmacokinetics profiles of HLX13 and originator ipilimumab. Results from these studies showed that there is a high similarity or no significant difference between HLX13 and originator ipilimumab.

Underpinned by the patient-centric strategy, Henlius has built an innovative product pipeline with high market potential targets, including PD-1/L1, CTLA-4, LAG-3, TIGIT, BRAF, etc., and has been pushing its early R&D research capabilities further while also upgrading the technology platform. Looking forward, Henlius will preserve its momentum for innovation by further strengthening the in-licensing and collaboration on external innovative assets and will continue strive for breakthroughs to bring more affordable and quality biologics to patients around the globe.

About NCT06159101
This randomised, single intravenous infusion, phase 1 parallel study aims to compare the pharmacokinetics, safety, and immunogenicity between HLX13 and ipilimumab (YERVOY, US-, EU-, and China-approved) in healthy Chinese adult male subjects. This study consists of two parts. Part 1 is an open-label, randomised, single-dose, two-arm, parallel study aiming to evaluate the pharmacokinetic parameters, safety, and immunogenicity after single intravenous infusion of HLX13 or EU-approved YERVOY, and to optimise the study design of Part 2. Part 2 is a double-blind, randomised, single-dose, four-arm, parallel study aiming to evaluate the similarity in pharmacokinetics among HLX13 and US-, EU-, and China-approved YERVOY, as well as their safety and immunogenicity. Subjects in the respective groups will receive 0.3 mg/kg of HLX13, or 0.3 mg/kg of US-, EU-, or China-approved YERVOY via intravenous infusion. The primary endpoints of this study are the area under the serum concentration-time curve from time 0 to infinity (AUC0-inf) and the maximum serum concentration (Cmax). Secondary endpoints include other pharmacokinetic parameters, safety, and immunogenicity.

Source: Shanghai Henlius Biotech, Inc.