AK112 头对头优于Keytruda，有望成为下一代IO治疗基石药物。据公司公告，AK112-303 是全球首个对比K药取得显著阳性的随机对照大III期研究，ITT组mFPS 11.14m vs. 5.82 月，HR=0.51（0.38-0.69），mFPS延长了5.3个月，取得显著性差异，ORR 50.0% vs 38.5%, DCR 89.9% vs 70.5%，证明AK112 在抗肿瘤效应上优于Keytruda。该临床入组基线，以及KeytrudamFPS和ORR表现与KNYNOTE-042 临床较为接近，符合我们预期。The company's recent situation
On September 8, the company announced in WCLC the clinical data of evosimab (AK112) compared with Keytruda for 1L treatment of PD-L1 positive NSCLC phase III. The ITT group MPFS 11.14m vs 5.82m, the ITT group HR reached 0.51, and the HR performance was stable in PD-L1 TPS 1-49%, TPS ≥ 50%, squamous cell carcinoma and non-squamous cell carcinoma subgroups. AK112 alone was superior to Keytruda. SUMMIT also announced that it will launch a phase III clinical trial of AK112 vs Keytruda to treat high 1L PD-L1 expression in '25. We believe this result further strengthens AK112's potential as an IO cornerstone product, including subsequent use with other drugs.
reviews
AK112 is superior to Keytruda head-to-head and is expected to become the cornerstone drug for the next generation of IO treatments. According to the company's announcement, AK112-303 is the world's first randomized controlled phase III study with significant positivity compared to K drugs. MFPs in the ITT group were 11.14m vs. 5.82 months, HR = 0.51 (0.38-0.69), and MFPs were extended for 5.3 months, and significant differences were obtained. ORR 50.0% vs. 38.5%, DCR 89.9% vs. 70.5%, proving that AK112 is superior to truda in anti-tumor effects. This clinical enrollment baseline, as well as KeytrudamFPS and ORR performance, are clinically close to knynote-042 and are in line with our expectations.
The efficacy of AK112 was stable in people with different PD-L1 expression levels. In people with PD-L1 TPS ≥ 50%, mPFS HR = 0.46; in PD-L1 TPS 1-49%, MPFSHr = 0.54. Based on this data, we believe that AK112 is expected to challenge the first-line position of Keytruda single drug in the treatment of NSCLC patients with high PD-L1 expression, and is also expected to reshape the PD-L1 low-expression NSCLC 1L treatment pattern and further expand the target population of the “chemotherapeutic” regimen.
The efficacy of AK112 was remarkable in both squamous cell carcinoma and non-squamous cell carcinoma subgroups. In the sqnsCLC population, MPFS HR = 0.48; in the nsQnsCLC population, MPFS HR = 0.54. In the past, IO monotherapy often did not perform well in squamous cell carcinoma. Immune combination chemotherapy is the mainstream choice for first-line treatment of advanced squamous cell carcinoma. Based on this data, we will further increase the probability of success in two phase III trials: AK112-306 (AK112+ chemotherapy vs. tirelizum+ chemotherapy, 1L sqnsCLC) and Harmoni3 (AK112+ chemotherapy vs. keytruda+ chemotherapy, 1L sqnsCLC).
The overall safety of Evosi is excellent, which is consistent with previous relevant studies. The incidence of AK112 and Keytruda grade 3 and above TRAE was 29.4% and 15.6%, respectively. The differences were mainly proteinuria, hypertension, and abnormal laboratory indicators. There was no significant increase in the risk of bleeding when treated with evosil compared to the control group. In sqnsCLC, the incidence of grade 3 TRAE between the two drugs was comparable (22.2% vs. 18.7%).
Profit forecasting and valuation
We keep our profit forecasts unchanged for 2024 and 2025. We maintain our outperforming industry rating. Based on the DCF model, based on the DCF model, we raised our target price by 5.7% to HK$70.00, which is 45.2% of the current stock price.
risks
Drug clinical data fell short of expectations; progress in the research pipeline fell short of expectations.
