The Zhitong Finance App learned that Open Source Securities released a research report saying that SCLC is highly aggressive and has a relatively poor prognosis. Currently, there is no effective targeted treatment for second- and third-line treatments. DLL3 is highly expressed in 80% of SCLC patients, providing a good solution for targeted therapy. Currently, only 1 product targeting this target has been approved for the market, and the competitive pattern is good. As more pipeline layouts and early research data are read in this field in the future, the track boom is expected to continue to improve, and related targets are expected to benefit.

The main views of Open Source Securities are as follows:

DLL3: SCLC's high-expression star target, high-profile BD transactions are frequent

DLL3 is a single transmembrane protein attached to the cell surface. It is a member of the Notch ligand family and is closely related to the enhancement of the ability of SCLC cells to proliferate, migrate, and invade. DLL3 is highly expressed in 80% of SCLC patients, and is expressed in small amounts or not in normal tissues, providing a good solution for targeted therapy. Heavy BD transactions are frequent in the DLL3 sector. In 2016, AbbVie purchased the DLL3ADC product ROVA-T, which was still in phase II clinical trials at the time, for 5.8 billion dollars in the StemCentrx pipeline; since November 2023, there have been 4 major transactions exceeding 0.1 billion dollars in the DLL3 sector, and the R&D boom continues to rise.

For DLL3 targets, various therapies such as ADC, double/triple antibodies, and CAR-T have been developed to specifically target DLL3 targets to kill tumor cells. Currently, only antalatumab, the CD3/DLL3 dual antibody product, has been approved for marketing. The rest of the pipelines are in phase II clinical trials and before, and the target competition pattern is relatively good.

SCLC: Highly invasive, poor prognosis. DLL3 targeted drugs may provide a new route for second- and third-line treatment

Small cell lung cancer (SCLC) is a malignant lung tumor originating in the bronchial mucosa or gland and accounts for about 15% of all lung cancer cases. Compared to non-small cell lung cancer (NSCLC), small cell lung cancer is more aggressive, can metastasize far in the early stages, and the prognosis is relatively poor. Currently, surgical resection, adjuvant radiation therapy, and adjuvant chemotherapy are still common treatments for limited-stage SCLC.

For broad-stage SCLC, the immunotherapy combination chemotherapy regimen is the first-line standard therapy; second-line treatment uses chemotherapy regimens such as irinotecan and rubitidine as standard therapy. DLL3 is highly expressed in 80% of SCLC patients, targeting drugs or providing new pathways for second- and third-line treatment.

One DLL3 target product has been approved for the market, and many early research pipelines have excellent curative effects

The failure to develop AbbVie's blockbuster DLL3ADC Rova-T was caused by multiple factors such as clinical protocol design and molecular structure design, which did not prove the pharmacogenicity of the DLL3 target. Taratumab (CD3/DLL3 dual antibody) was approved and marketed by the FDA in May 2024. The third-line treatment for SCLC MPFs is about 3-5m; compared with taratumab, Zejing Pharmaceutical's ZG006 (CD3/DLL3 triple antibody) and Zaiding Pharmaceutical's ZL-1310 (DLL3ADC) showed better response rates (ORR 66.70% and 74.00%, respectively), and the overall safety is good, and there is great potential for future clinical development.

Investment advice

Recommended target: Zejing Pharmaceutical-U (688266.SH);

Beneficiaries: Hengrui Pharmaceutical (600276.SH), BeiGe Shenzhou-U (688235.SH), China Biopharmaceutical (01177), Cinda Biotech (01801), Baili Tianheng-U (688506.SH), Zaiding Pharmaceuticals (09688).

Risk warning: Decline in the popularity of innovative drug development, failure in clinical drug development, drug safety risks, etc.