If you want to speculate in the stock market, you can see the research report of Jin Kirin analysts.GovernorofpokerdownloadAuthoritative, professional, timely, comprehensive, to help you tap the potential theme opportunities!

Jin Zhe, a journalist, has many articles per editor.

"Today's scene really startled me, because I thought everything was good news. I expect [the stock price] to go in the other direction. " At noon on Friday, May 24th, in a conference call with investors, HK09926 (37%)Governorofpokerdownload.05 Hong Kong dollars, with a market capitalization of 32.1 billion Hong Kong dollars) Chairman Xia Yu said slightly helplessly: "We still think this is quite (surprising) at first."

At 09:30 that day, Kangfang Bio's shares fell sharply after opening, falling more than 40% at one point in intraday trading and closing down 28.2% by midday, the lowest since December 2022. According to market news, the information disclosed by the American Society of Clinical Oncology (ASCO) shows that the Chinese phase III clinical data of AK112 in the treatment of EGFR-TKI (a targeted treatment) are lower than expected.

A reporter from the Daily Business News noticed that more than 1500 investors from the pharmaceutical industry attended the impromptu investor briefing. Xia Yu explained at the meeting that in the summary of this ASCO annual meeting, OS (overall survival) data were not disclosed, but in fact, the overall survival data of the test group obviously showed a benefit trend, which was two completely separate curves from the control group.

"internally, we will find this figure very eye-catching." Xia Yu said that the relevant overall survival data will be released to the world in the form of an oral report at the upcoming ASCO conference.

The "small composition" caused the stock price to fall sharply.

On May 24th, the summary of ASCO's 2024 annual meeting was announced. The ASCO website publishes a summary of AK112-301 research data, including summary data on progression-free survival (PFS) at the main end point of the study.

AK112/SMT112 is a bispecific antibody against PD-1/VEGF (programmed death receptor 1 / vascular endothelial growth factor). Previous phase I / II clinical studies have shown that EGFR-TKI has potential efficacy in patients with EGFR (epidermal growth factor receptor) mutations in non-small cell lung cancer (NSCLC) who failed in previous AK112 treatment. The purpose of this phase Ⅲ study was to evaluate and confirm the efficacy and safety of ivacizumab combined with chemotherapy compared to standard therapy in this population.

A total of 322 patients were randomly assigned, of which 161 were enrolled in the ivacizumab + chemotherapy group and 161 in the placebo + chemotherapy group.

After the opening of trading in the morning, a quiet storm swept from the other side of the ocean to Hong Kong stocks and A shares, led by Kang Fang Bio, the new drug plate fell sharply. A reporter from the Daily Business News found that the source of the storm was a "small composition" circulated on WeChat, which not only disclosed the clinical data of AK112 III in the ASCO summary, but also added a comment that "the clinical data are not as good as expected." Some people in the pharmaceutical industry told reporters that the evaluation was based on the data of "Cinda Biological PD-1 Cindilizumab + bevacizumab chemotherapy" treatment regimen.

It is understood that the above clinical data compared with Ivosi come from a trial called ORIENT-31. This study is a randomized, double-blind, multicenter, three-phase randomized, double-blind, multicenter study of patients with EGFR mutant non-small cell lung cancer who failed to be treated with EGFR-TKI. The purpose of this study was to explore the clinical efficacy and safety of PD-1 inhibitor Xindirizumab combined with or without bevacizumab and chemotherapy in this specific population.

On the same day's conference call, Dr. Li Baiyong, co-founder and chief scientific officer of Kangfang Biological Co-founder, said that he had also heard some feedback about PFS in the morning. In fact, the analysis of clinical research data is a very professional and complex process, and it can not be evaluated only according to the absolute value of PFS. Cross-study non-head-to-head comparison, which is statistically unscientific, even if two studies with the same indications The difference in baseline of patients enrolled in the group will also directly lead to differences in PFS data. In addition, the comparison between the data of the second phase of the cross-study and the data of the third phase of the study can not explain the problem. "We also see that a lot of small sample data including monoclonal antibodies or ADC (antibody drug coupling technique) work well, but in the end, it is uncertain whether this efficacy can continue to be reflected in phase III clinics. there are many precedents for phase II data to be excellent but phase III studies have failed." Li Baiyong said.

"the core indicator for evaluating the results of clinical studies is the benefit-risk ratio (HR), which really shows the benefits of blind randomized controlled trials. The PFS studied by AK112-301 has obtained the result of 'HR=0.46', which is an excellent result. " Li Baiyong said.

According to the data of open market comparison, according to the subgroup analysis, the benefit-risk ratio of base-line brain metastasis in AK112-301 study PFS was 0.40 (exon 19 deletion) and 0.48 (a drug-resistant mutation) was 0.22. In contrast, the benefit-risk ratio of brain metastases was 0.84 and the loss of exon 19 was 1.04 and the benefit-risk ratio of T790M mutation was 1.1.

The chairman said the clinical data were eye-catching

"We all felt that the data was very eye-catching, but the market gave a completely different interpretation." Xia Yu originally thought that with so many favorable landings, the company's share price should rise.

After the opening of trading on the morning of the 24th, Xia Yu was originally in an interview when she suddenly saw her colleagues waving to her outside the court. She "did not expect to talk about this situation (the stock price fell)."

Despite the emergence of a "black swan" in the stock price, Xia Yu is confident about Yvosi's data. According to her, Yvosi obtained excellent data on PFS and showed a good trend of benefit on OS (overall survival time). It is precisely based on this data that Ivosi was approved by the State Drug Administration on May 24th, and these excellent data will further support overseas ongoing phase III clinical studies in which all enrolled patients are third-generation TKI-resistant.

In the population with EGFR mutation, brain metastasis is the focus of attention. According to Xia Yu, first of all, among the clinical participants of AK112, the number of brain metastases is very sufficient, which is closest to the actual clinical situation in the real world.

She further introduced: Clinical results show that it controls brain metastases well, which is one of the highlights of this clinical results; in addition, from the analysis of subgroup data, Kangfang Biotech's data "are comprehensive and excellent data" in the status of brain metastases and liver metastases.

There is also another concern. More than 80% of the patients in this subject have undergone three-generation TKI targeted therapy. In clinical practice, due to multiple practical factors, patients who are resistant to third-generation TKIs usually in worse physical condition than patients who use only one or two generations of TKIs. The worse the baseline situation, the absolute value of their progression-free survival will inevitably be affected. Some clinicians believe that resistance to third-generation TKI drugs is the main clinical problem in the current treatment of such diseases. For example, the United States basically uses third-generation TKI drugs as first-line treatment, so they are of more practical clinical significance.

Xia Yu also said that because part of the product data will be used in the project of the company's partner Summit Company-especially the restrictions on data publication requirements involving the ASCO conference, the company is more cautious about the disclosure of Ivosa's clinical data. In the current abstract, gold standard data such as overall survival is not disclosed, but as this product is approved in China, it will be visible in detail on the drug instructions immediately.

The reporter noted that on May 24, AK112 was approved by the State Food and Drug Administration for marketing. It was combined with pemetrexed and carboplatin for use in locally advanced or metastatic non-squamous non-small cell lung cancer that progressed after EGFR-TKI treatment.

During this telephone conference, Xia Yu also mentioned that the capabilities of Kangfang Biotech's commercial sales team have been well verified. Although the new dual anti-drug drug Cardonil has not been covered by medical insurance and has few indications, it has a good market and clinical performance. "Three years ago, no one in the industry or hospitals knew about 'Kangfang'. Now if you ask clinical experts, how many people don't know about' Kangfang'? This is the result of the practical clinical value of the drug."

In 2023, Kangfang Biotech achieved annual profit for the first time, with total annual revenue of 4.526 billion yuan, a year-on-year increase of 440%, and a profit attributable to owners of the parent company of 2.028 billion yuan.

She also said that the company's next focus is sales of AK112. "I have heard many doctors say they are looking forward to this drug, so we are full of confidence in our future sales, so at this point, don't worry about it."

The reporter of "Daily Economic News" noticed that the telephone meeting with Kangfang Biotech's management had obvious results. On the afternoon of May 24, Kangfang Biotech quickly rose, and the decline narrowed. As of the close, it was reported at HK$37.05/share, down 22.89%.