The company recently held an investor meeting and invited key researchers from the Phase III Harmoni-A trial (EVOSIL to treat EGFR-TKI-resistant NSCLC) for further interpretation. We have summarized the main points as follows:
The success rate of overseas research is high: the OS HR was 0.80 (95% CI 0.59-1.08) when the maturity of the Harmoni-A test data reached 52%, and the OS curve showed a trend of further differentiation (previously reported). Experts believe that global Harmoni trials are more likely to achieve significant OS efficiency, considering: 1) there are few successful studies similar to ORIENT-31, development of HER3 ADC in terminal treatment is blocked, I/O and ADC drugs have not been successful in this indication, and have not met clinical needs overseas; 2) the reason why Harmoni-A OS HR statistics are not significant may be related to patients using innovative drugs such as PD-1 at their own expense in subsequent treatment. Considering significantly higher drug pricing in the US, this phenomenon is less likely to occur in the US, and OS data will be less disrupted by subsequent treatment; 3) Even if OS HR is not significant, it does not mean that approval for marketing is denied. The curve shape and follow-up treatment are also key considerations. Refer to Tagrisso's FLAURA and AURA3 studies, as well as Rybrevant (one of the EGFR-TKI-resistant NSCLC, MARIPOSA-2 study).
Excellent safety data may be another key to victory: in the Harmoni-A trial, overall safety was good, and the incidence of grade 3 or above TRAE was manageable (treatment group vs. Placebo group: 54.0% vs.
42.9%), including the discontinuation rate (5.6% vs. 2.5%), grade 3 or above iRAE (6.2% vs. 2.5%), and VEGF-related TRAE (3.1% vs. 2.5%). Among the key safety events, hypothyroidism, proteinuria, bleeding, etc. are mostly grade 1-2, and can be well controlled through medication and continuous observation. In contrast, in the MARIPOSA-2 study, the incidence of grade 3 or above AE in both Rybrevant treatment groups was over 70% (72%/92% vs. 48%), and the discontinuation rate was much higher than that of the placebo group (18%/34% vs. 4%).
Reiterating the purchase: We maintain the purchase rating and target price of HK$70, and focus on: 1) the publication of AK112-303 head-to-head K drug data at the September WCLC conference (summary will be announced on August 15, Beijing time), and the PFS HR was significantly lower than 0.7 (strong positive results); 2) the progress of negotiations on the two new bipolar drugs in this year's health insurance negotiations. Recently, the price of ketani was reduced by 53%, increasing the probability of successful negotiations; 3) the development of an IO+ADC combination scheme based on the dual-antibody IO base variety.