Yasheng Pharmaceutical-B (06855.HK) released the data of the Ib phase clinical trial of original target Bcl-2/Bcl-xL inhibitor pelcitoclax (APG-1252) combined with oxitinib in the treatment of EGFR TKI-resistant non-small cell lung cancer (NSCLC) in the form of a small oral report at the World Lung Cancer Congress. APG-1252 is a Bcl-2/Bcl-xL dual-target inhibitor independently developed by Yasheng Pharmaceutical, which can repair cell apoptosis by selectively inhibiting Bcl-2 and BclxL proteins at the same time. Previous animal models have shown a synergistic anti-tumor effect in combination with oxetinib in NSCLC patients who are sensitive to or resistant to oxetinib.

Phase Ib clinic showed good safety and tolerance, and the anti-tumor synergistic effect of APG-1252 was preliminarily observed in some patients with oxetinib resistance. The disease control rate (DCR=80%,) and objective remission rate (ORR=15%) for the oxetinib resistance cohort (nystinib 20). Compared with the previous Rybrevant with the highest drug resistance to oxetinib (JNJ-6372, phase I data of oxetinib resistance nyst45, the total effective rate of DCR=60%, was 36%).

The potential market for third-generation EGFR TKI resistance is huge: ASCO data show that 30% of lung cancer patients have EGFR mutations. The third generation EGFR TKI drugs have achieved great success in solving the drug resistance problem of the first two generations (T790M mutation resistance accounted for half of the patients) and good tolerance. After oxetinib and ametinib are included in the health insurance, it is expected that the domestic third-generation EGFR TKI market will expand rapidly, with a peak sales exceeding 15 billion yuan. The problem of oxetinib resistance (second-line drug resistance usually occurs in 10 months) is currently the biggest pain point in the field of EGFR and is expected to expand rapidly with the third-generation EGFR TKI market. At present, the main ideas for the treatment of oxetinib resistance are 1) combined with gefitinib for T797s trans mutation, or first-line treatment to delay the occurrence of drug resistance; 2) Bugatinib combined with cetuximab for T797s cis-mutation; 3) combined with valitinib to deal with MET amplification + EGFR mutation positive, 4) EGFRMET double antibody (JNJ-6372) to deal with MET amplification. However, it is known that the cause of the mutation is only a small part of the first-and second-line oxetinib resistance, and the drug resistance mechanism of the third generation TKI is also very different, and the cause of drug resistance is unknown. The combination of APG-1252 and oxetinib through the target of Bcl-2/xl apoptosis pathway is a new therapeutic idea, which is expected to achieve clinical benefit.

Investment advice: we believe that APG-1252 shows a good prospect of drug resistance against third-generation EGFRTKI. However, it is still in the early stage and more security and effectiveness data are needed. On the whole, we are optimistic about the prospect of combined drug use of apoptosis mechanism and the company's leading R & D strength in this field. There is no shortage of catalysts in the short term, so it is recommended to buy.