Recently, Shanghai Medicilon Inc. (Medicilon) has successfully obtained an invention patent from the National Intellectual Property Administration for its self-developed project titled "Antibodies Targeting Nectin-4 and Their Various Applications"!
The successful granting of this patent not only recognizes Medicilon's deep expertise and technical strength in the field of cancer antibody drug development but also enriches its technological reserves. This advancement provides cutting-edge technical support and service assurance to enhance the drug development efforts of its clients.
Nectin-4 Structure (Image Source: Nature Drug Discovery)
Nectin-4 is a protein encoded by the poliovirus receptor-related 4 (PVRL-4) gene. It is an immunoglobulin-like protein that does not depend on Ca2+ for its function. Nectin-4 interacts with other adhesion proteins such as Nectin-1, Nectin-2, and Nectin-3 to participate in cell-cell adhesion. Compared to other Nectin proteins, Nectin-4 is specifically enriched in human embryonic and placental tissues, with its expression significantly decreasing in adults. In recent years, research has found that Nectin-4 is notably overexpressed in various malignant tumors, including breast cancer, lung cancer, colorectal cancer, pancreatic cancer, and ovarian cancer. It acts as a tumor-associated inducer in these cancers. In some types of cancer, the overexpression of Nectin-4 is associated with various aspects of tumor progression, such as proliferation, angiogenesis, epithelial-to-mesenchymal transition, metastasis, DNA repair, tumor recurrence, and poor prognosis (Subhajit et al., 2021).
In solid tumors, Nectin-4 can promote tumor proliferation and migration by activating the PI3K/Akt signaling pathway (Akai et al., 2008a, b). Nectin-4 has two interesting characteristics: On one hand, as a cell surface receptor that mediates the entry of the measles virus into cells, Nectin-4 exhibits inducible and efficient internalization, which can facilitate the effective endocytosis of antibody drugs. On the other hand, while Nectin-4 is expressed at limited levels in healthy adult tissues, it is overexpressed in malignant tumor cells. This differential expression pattern enables targeted drug therapy, minimizing the risk of adverse events. Given these characteristics, Nectin-4 has become an attractive target for targeted therapy. Its significant clinical potential has been further demonstrated through the development of targeted ADCs (antibody-drug conjugates).
Nectin-4 is involved in tumorigenesis and metabolic mechanisms (Source: Wafa Bouleftour et al., 2023)
In 2019, the first-generation ADC drug targeting Nectin-4, Padcev (Enfortumab Vedotin-ejfv), received accelerated approval from the FDA for the treatment of urothelial carcinoma. It is currently approved as a first-line treatment for patients with locally advanced or metastatic urothelial carcinoma who are not suitable for cisplatin-based chemotherapy, offering a groundbreaking improvement in patient survival. At the 2024 ASCO conference, the Nectin-4 ADC further solidified its status as a major unmet clinical need (mUC BIC), demonstrating broad potential for application across various cancer types. These developments not only highlight the value of the Nectin-4 target but also provide Medicilon with valuable experience and references for pharmaceutical companies developing similar drugs.
Mechanism of Action of Enfortumab Vedotin (Image Source: Seagen website)
Currently, there are 10 targeted therapies against Nectin-4 in various stages of preparation or clinical trials worldwide. This includes 8 ADC drugs and 2 peptide-drug conjugates (PDCs). Among them, 9MW2821 is particularly notable. Its Phase III clinical trial for urothelial carcinoma is progressing smoothly, making it the second most advanced globally and the leading one in China. In addition, the drug also demonstrates a leading position globally in the development of other indications, such as colorectal cancer (CC), endometrial cancer (EC), and triple-negative breast cancer (TNBC).
Medicilon has been granted a national invention patent for "Antibodies Targeting Nectin-4 and Their Applications," based on in-depth research and understanding of this target. Relying on Medicilon's single B-cell antibody discovery platform, Medicilon has successfully screened a series of new antibody sequences targeting Nectin-4. These antibody sequences not only exhibit high specificity and affinity but also demonstrate good drug-like properties and potential therapeutic value.
The acquisition of this patent not only diversifies the antibody library targeting Nectin-4 but also positions Medicilon as a CRO partner capable of offering more innovative research options and faster development processes to its clients.
About Medicilon's Single B-Cell Antibody Discovery Platform
Medicilon provides single B-cell antibody production technology services, including single B-cell sorting, single B-cell Ig gene transcription, amplification, and sequencing. The single B-cell antibody production technology is one of the novel and efficient antibody discovery methods. It offers advantages such as fast speed, high throughput, and the natural pairing of antibody heavy and light chain variable regions.
Looking ahead, Medicilon, as an enabler in the field of preclinical biopharmaceutical research and development, will continue to focus on technological innovation and continuously upgrade its service platforms. The goal is to provide clients with cutting-edge, high-quality, and efficient services to support their drug development efforts. At the same time, Medicilon will actively benchmark against international cutting-edge research technologies, maintain a keen market foresight, and continually explore win-win collaboration opportunities with top global partners to jointly advance the development of the global biopharmaceutical industry.
Relevant
news
marketing@medicilon.com
