According to a research report released by Kaiyuan Securities, SCLC is highly aggressive and has a relatively poor prognosis, and there is a lack of effective targeted therapy drugs for second- and third-line treatments. DLL3 is highly expressed in 80% of SCLC patients, providing a good solution for targeted therapy. At present, only one product has been approved for marketing for this target, and the competition pattern is good. With more and more pipeline layouts and early research data readout in this field in the future, the track prosperity is expected to continue to improve, and related targets are expected to benefit.

The main views of Kaiyuan Securities are as follows:

DLL3: SCLC high-expression star target, blockbuster BD transactions are frequent

DLL3 is a single-shot transmembrane protein attached to the cell surface, which is a member of the Notch ligand family and is closely related to the enhancement of the proliferation, migration and invasion ability of SCLC cells. DLL3 is highly expressed in 80% of SCLC patients, but is expressed in small amounts or even no in normal tissues, providing a good solution for targeted therapy. In 2016, AbbVie acquired Rova-T, a DLL3ADC product in Stemcentrx's pipeline that was still in Phase II clinical trials at the time, for $5.8 billion; Since November 2023, there have been 4 blockbuster transactions of more than $100 million in the DLL3 field, and the R&D boom continues to increase.

For DLL3 targets, a variety of therapies such as ADCs, bispecific antibodies/triple antibodies, and CAR-T have been developed to specifically target DLL3 targets to kill tumor cells. At present, only Amgen's CD3/DLL3 bispecific antibody product taratuzumab has been approved for marketing, and the rest of the pipelines are all in Phase II clinical trials and before, and the target competition pattern is good.

SCLC: highly aggressive and poor prognosis, DLL3-targeted drugs may provide a new avenue for second- and third-line treatment

Small cell lung cancer (SCLC) is a lung malignancy that originates from the bronchial mucosa or glands, accounting for about 15% of all lung cancer cases. Compared with non-small cell lung cancer (NSCLC), small cell lung cancer is more aggressive, distant metastases can occur at an early stage, and the prognosis is relatively poor. For limited-stage SCLC, surgical resection, adjuvant radiotherapy, and adjuvant chemotherapy are still common therapies.

For extensive-stage SCLC, immunotherapy plus chemotherapy is the first-line standard of care; Second-line treatment uses chemotherapy regimens such as irinotecan and rubitidine as standard therapy. DLL3 is highly expressed in 80% of SCLC patients, and targeted drugs may provide a new avenue for second- and third-line treatment.

One product of DLL3 target has been approved for marketing, and a number of early research pipelines have excellent efficacy

The failure of AbbVie's blockbuster product DLL3ADC Rova-T is caused by multiple factors such as clinical protocol design and molecular structure design, which cannot prove the druggability of DLL3 targets. Talateumab (CD3/DLL3 bispecific antibody) has been approved by the FDA in May 2024 for the third-line treatment of SCLC mPFS of approximately 3-5m; Compared with taratumab, Zelgen's ZG006 (CD3/DLL3/DLL3 triple antibody) and Zai Lab's ZL-1310 (DLL3ADC) have demonstrated better response rates (ORR of 66.70% and 74.00%, respectively), and have an overall good safety profile, indicating great potential for clinical development in the future.

Investment advice

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

Beneficiary targets: Hengrui Pharma (600276.SH), BeiGene-U (688235.SH), Sino Biopharma (01177), Innovent Biologics (01801), Baili Tianheng-U (688506.SH), Zai Lab (09688).

Risk warning: the decline in the research and development of innovative drugs, the failure of drug clinical research and development, and the risk of drug safety.