Zhitong Finance App News, Weilizhibo-B (09887) announced that the first patient was enrolled in an open, multi-center phase IB/II clinical trial of Velisin® (opatisumimab, PD-L1/4-1BB bispecific antibody) combination developed independently by the Evaluation Group to treat metastatic colorectal cancer (mCRC). This marks a further extension of the company's strategy to target immunity against “cold tumors” with Velisign®, from extrapulmonary neuroendocrine cancer (“EP-NEC”), biliary tract cancer (“BTC”), hepatocellular carcinoma (“HCC”), and platinum-resistant ovarian cancer (“PROC”).
In mCRC, patients with microsatellite-stabilized (“MSS”) and complete mismatch repair (“pMMR”) account for approximately 95% of patients. Due to insufficient T cell infiltration in the tumor microenvironment, this patient group has extremely low response to traditional immune checkpoint inhibitors. Standard treatment is still mainly based on chemotherapy combined with targeted therapy, and new treatment strategies are urgently needed. Velisign® conditionally activates 4-1BB to reactivate and massively amplify T cells while relieving PD-1/PD-L1 immunosuppression, which is expected to fill the immunotherapy gap in this patient group and bring long-lasting survival benefits.
The Phase Ib/II clinical trial, led by Academician Xu Ruihua of the Sun Yat-sen University Tumor Prevention Center, will be carried out simultaneously in many hospitals across the country to evaluate the efficacy and safety of Velissin® in mCRC patients. Verisign® translational medicine research for MSS colorectal cancer has been selected for the 2026 European Society of Medical Oncology (“ESMO”) poster presentation. At the same time, Velisign® has shown a significantly longer survival benefit trend compared to historical data in many typical immune “cold tumor” indications such as EP-NEC, BTC, HCC, and PROC, providing mechanistic and clinical support for the development prospects of Velisign® for mCRC indications.
CRC is the most common digestive malignancy worldwide. According to the International Agency for Research on Cancer (“IARC”), there were about 1.93 million new cases of CRC and 904,000 deaths in 2022, making CRC the third most common confirmed cancer and the second leading cause of cancer-related deaths in the world. According to data released by China's National Cancer Center, there were 517,000 new CRC cases and 240,000 deaths in China in 2022. The incidence rate and death rate ranked second and fourth among all malignant tumors, respectively. Approximately 15% to 30% of CRC patients had distant metastases at the time of initial diagnosis, while 20% to 50% of patients with initial localized CRC eventually developed mCRC. Despite advances in treatment, mCRC still has poor prognosis, with a 5-year survival rate of only about 15%. Currently, immunotherapy is mainly approved for CRC patients with highly unstable microsatellites (MSI-H) or mismatch repair defects (dMMR). However, in mCRC, these patients account for only about 5%, while about 95% are microsatellite-stabilized (MSS) or mismatched repair complete (pMMR) groups. The response to traditional immunotherapy is generally limited, and there is a huge unmet medical need.
Velisign® is a bispecific antibody that targets both PD-L1 and 4-1BB, and has the potential to become a pan-tumor IO 2.0 cornerstone therapy with survival benefits. Currently, Verisign® has carried out clinical studies for 14 indications, including 1 single-arm critical registration clinical study, 1 confirmatory phase III clinical study, and 9 proof-of-concept studies, covering multiple major cancer types and “cold tumors”. Among the 7 types of cancer supported by clinical data, Verisign® has shown excellent clinical value and broad treatment prospects, including extrapulmonary neuroendocrine cancer (EP-NEC), non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), biliary tract cancer (BTC), hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), and ovarian cancer (OC).
Developed by X-body™, a platform independently developed by the Application Group and with full intellectual property rights, Velisin® can conditionally activate 4-1BB, remove PD-1/PD-L1 immunosuppression while enhancing T-cell activation regulated by 4-1BB, and achieve the effect of collaboratively eliminating tumors. Velisign® is as safe as PD-1/PD-L1 inhibitors and has greater potential for broad-spectrum cancer treatment. In particular, it is worth pointing out that activating 4-1BB can reactivate depleted T cells and expand massively, so that therapeutics targeting 4-1BB may be suitable for treating immunological “cold tumors” that are resistant or ineffective against PD-1/PD-L1 inhibitors, and can bring survival benefits with long-lasting effects.
In October 2024, Velisin® was recognized as a breakthrough therapeutic drug by the NMPA; in November 2024, it was certified as an orphan drug by the US Food and Drug Administration (“FDA”). In January 2026, Velisign® was granted FDA Fast Track certification and EU orphan drug certification. In September 2026, Velisign® was certified as an orphan drug by Japan's Ministry of Health, Labor, and Welfare (“MHLW”). In July 2026, the marketing application for Velisign® innovative biological products was included in the priority review and approval process by the NMPA and officially accepted in August 2026. It is expected to become the world's first approved 4-1BB antibody drug, the world's first approved agonist antibody drug, and the world's first approved therapeutic drug for EP-NEC.