Leads Biolabs-B (09887) has announced that the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has formally accepted the company's independently developed investigational drug, Velixin™ (opasutsumab, a PD-L1/4-1BB bispecific antibody, LBL-024), for a New Drug Application (NDA).
The NDA seeks approval for Velixin™ as a monotherapy in treating advanced extrapulmonary neuroendocrine carcinoma (EPNEC) in patients who have undergone prior treatment. This submission marks Velixin™ as the first PD-L1/4-1BB bispecific antibody globally to enter the NDA stage, having already received priority review designation from the CDE on July 10, 2026.
If approved, Velixin™ would represent a significant milestone in China's innovative drug landscape, becoming the first antibody drug worldwide to directly target the 4-1BB receptor and the first agonist antibody approved for any indication. This would also establish 4-1BB as the fourth validated immunotherapy target globally, following PD-1/PD-L1, CTLA-4, and LAG-3.
The NDA submission is based on positive results from a pivotal registration clinical study led by Professor Shen Lin from Peking University Cancer Hospital, involving 34 hospitals. The study completed enrollment of all 96 EPNEC patients in August 2025, with detailed clinical findings planned for presentation at leading international academic conferences.
Neuroendocrine carcinoma (NEC) represents a highly malignant immunologically "cold" tumor, comprising approximately 10% to 20% of neuroendocrine neoplasms. NEC can arise in various organs, including the lungs, digestive tract, and bladder, and is classified into pulmonary NEC and EP-NEC. EP-NEC shares aggressive invasion and metastasis characteristics with small cell lung cancer (SCLC), with rapid disease progression, and most NEC patients present with advanced disease or distant metastasis at diagnosis.
Current systemic treatment options for NEC are limited, with poor efficacy and unfavorable prognosis. Globally, no regulatory authority has yet approved a drug specifically for EP-NEC treatment. First-line therapy for advanced EP-NEC primarily relies on platinum-based chemotherapy, achieving objective response rates (ORR) of approximately 30% to 50%, with median overall survival (mOS) of only about one year. After first-line treatment failure, no standard second-line regimen exists, with options including oxaliplatin-based FOLFOX, irinotecan-based FOLFIRI, CAPTEM with or without bevacizumab, or temozolomide monotherapy. However, these approaches demonstrate limited efficacy, with ORR around 10% to 25% and mOS of approximately 8 months, leaving a substantial unmet clinical need for advanced EP-NEC patients.
Velixin™ is a bispecific antibody simultaneously targeting PD-L1 and 4-1BB, designed as a potential pan-tumor IO2.0 cornerstone therapy with survival benefits. Developed using Leads Biolabs' proprietary X-body™ platform with fully owned intellectual property, Velixin™ conditionally activates 4-1BB, relieving PD-1/PD-L1 immunosuppression while enhancing 4-1BB-mediated T-cell activation to achieve synergistic tumor elimination. The drug demonstrates safety comparable to PD-1/PD-L1 inhibitors while showing stronger broad-spectrum anticancer potential, with first-in-class (FIC) or best-in-class (BIC) promise observed across tumors including non-small cell lung cancer (NSCLC), SCLC, EP-NEC, and biliary tract cancer (BTC).
As the first molecule targeting the co-stimulatory receptor 4-1BB in single-arm pivotal registration clinical stage globally, Velixin™ is positioned to become the first approved therapy for EP-NEC. The company has initiated clinical studies across 13 solid tumor indications in China, including one pivotal registration trial and eight proof-of-concept studies, covering EP-NEC, NSCLC, SCLC, BTC, ovarian cancer (OC), esophageal squamous cell carcinoma (ESCC), hepatocellular carcinoma (HCC), gastric cancer (GC), triple-negative breast cancer (TNBC), and malignant melanoma—all areas of high unmet need.
Notably, activating the 4-1BB co-stimulatory pathway can restore and enhance the activity of exhausted T cells and promote their expansion, potentially making 4-1BB-targeted therapies applicable to immunologically cold tumors that are resistant or unresponsive to PD-1/PD-L1 inhibitors, with potential for long-tail durable survival benefits. Velixin™ received Breakthrough Therapy Designation from the NMPA CDE in October 2024, followed by Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) in November 2024. In January 2026, the drug obtained FDA Fast Track designation and Orphan Drug Designation from the European Union.