China’s National Medical Products Administration has granted a second Breakthrough Therapy Designation to Innovent Biologics’ IBI363, a first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein, for treating immunotherapy-resistant squamous non-small cell lung cancer (sqNSCLC). The designation applies to unresectable, locally advanced, or metastatic sqNSCLC that has progressed following anti-PD-(L)1 immunotherapy and platinum-based chemotherapy. This marks IBI363’s fourth regulatory recognition, adding to existing NMPA BTD and FDA Fast Track designations for both sqNSCLC and melanoma indications.
The regulatory milestone follows encouraging Phase 1 data presented at the 2025 ASCO Annual Meeting, demonstrating manageable safety profiles and efficacy signals across multiple immunotherapy-resistant tumor types. IBI363’s dual-mechanism approach combines PD-1 blockade with IL-2-driven expansion of tumor-specific T-cell populations, designed to reshape the tumor microenvironment. The IL-2 component maintains affinity for IL-2Rα while reducing binding to IL-2Rβ and IL-2Rγ, potentially minimizing toxicity compared to traditional IL-2 therapies.
The regulatory priority addresses a significant clinical gap in sqNSCLC management. For patients who have failed immunotherapy and lack driver gene mutations, current standard treatments like docetaxel offer limited efficacy with a median progression-free survival of under four months. Recent Phase 3 antibody-drug conjugate studies in sqNSCLC have shown disappointing results, highlighting the urgent need for novel therapeutic approaches in this immunotherapy-resistant population.
“IBI363 could potentially be a promising next-generation IO agent by combining dual mechanisms—PD-1 blockade and IL-2-driven tumor-specific T-cell population expansion, thus reshaping the tumor microenvironment,” stated Dr. Hui Zhou, Senior Vice President of Innovent. The company is advancing its first registrational study in acral and mucosal melanoma and plans discussions with regulators regarding additional pivotal trials for lung cancer and colorectal cancer indications.
With lung cancer representing the most common and deadliest malignancy globally, and sqNSCLC comprising a significant subset of the 80% NSCLC cases, IBI363’s differentiated mechanism could capture substantial market share in the immunotherapy-resistant setting. The NMPA BTD provides accelerated review pathways and enhanced regulatory guidance, potentially shortening development timelines for this high-unmet-need population. Innovent’s global development strategy, spanning China, the United States, and Australia, positions IBI363 for broad commercial potential pending successful Phase 3 outcomes.
