Nanjing Leads Biolabs Co., Ltd. has successfully dosed the first patient in the Phase II trial of LBL-034, a GPRC5D/CD3 bispecific T-cell engager, marking a significant milestone in the development of what could become China's first domestic T-cell engager therapy targeting GPRC5D. The advancement follows strong Phase I data demonstrating CAR-T-like efficacy in treating relapsed/refractory multiple myeloma.
Promising Phase I Results Drive Clinical Advancement
LBL-034 demonstrated strong efficacy signals and a favorable safety profile among over 50 enrolled patients at dose levels up to 1,200 μg/kg in its open-label, multi-center, dose-escalation/expansion Phase I trial. At higher doses, the therapy showed robust objective response rates similar to CAR-T treatment, with particularly promising efficacy observed in the challenging subgroup of patients with extramedullary plasmacytomas.
The minimal residual disease negativity rate was significantly higher than current standard of care treatments. According to the company, detailed results including efficacy, safety, pharmacokinetics/pharmacodynamics, biomarker, and exposure-response analyses will be presented at the 2025 American Society of Hematology Annual Meeting.
Innovative Design Targets Safety and Efficacy
LBL-034 features a uniquely designed 2:1 format with two binding sites targeting GPRC5D and one targeting CD3. By optimizing anti-CD3 affinity and steric hindrance, the therapy effectively redirects and activates T cells to target GPRC5D-positive cancer cells while being less prone to inducing nonspecific T-cell activation. This design aims to minimize T cell exhaustion and cell death while reducing the risk of cytokine release syndrome and immunotoxicity.
"The successful dosing of the first Phase II patient marks a critical step in our TCE pipeline and validates our unique molecular design," stated Dr. Charles Cai, Chief Medical Officer of Leads Biolabs. "We will continue advancing clinical development with high standards to deliver China's first GPRC5D-targeted TCE therapy, offering patients safer and more effective options."
Multi-Center Phase II Trial Design
The Phase II trial is a multi-center, single-arm, multi-cohort clinical trial led by Professor Lu Jin of Peking University People's Hospital, with participation from over 20 hospitals across China. The study aims to evaluate the efficacy and safety of LBL-034 in patients with various relapsed/refractory plasma cell neoplasms.
Global Competitive Position
According to Frost & Sullivan data from November 2024, LBL-034 is the second most clinically advanced GPRC5D-targeted CD3 T-cell engager globally and the first in China in terms of clinical progress. The therapy received orphan drug designation from the FDA for multiple myeloma treatment in October 2024.
Dr. Xiaoqiang Kang, Founder, Chairman and CEO of Leads Biolabs, emphasized the broader implications: "LBL-034's exceptional Phase I data and smooth Phase II initiation underscore the core advantage of our Leadsbody™ platform—conditional activation. This success bolsters confidence in our broader pipeline and accelerates breakthroughs in TCE therapies for solid tumors, hematologic malignancies, and autoimmune diseases."
The advancement represents a significant step forward for Leads Biolabs' proprietary LeadsBody™ platform, which serves as the foundation for the company's bispecific antibody development and has been validated by clinical outcomes across their portfolio.
