The history of biomedicine always needs to be written, although the current industry mood is quite pessimistic, but when the industry "clearing" is completed, the final competition is still the speed and process of research and development.

Take FGFR, one of the hot targets of "unlimited cancer" therapy, for example, according to Southwest Securities Research report, there are a total of 13 FGFR4 inhibitors in clinical research worldwide. It seems that there are many products in the research and development, but in fact, there are only three small molecular inhibitors of FGFR4 in clinical research. The rest, such as Novartis roblitinib and Incyte INCB62079, actively terminated the development. Blueprint's fisogatinib, H3 Biomedicine's H3B6527, Nuocheng Jianhua's ICP-105, Zhongsheng Pharmaceutical's ZSP-1241, Hausen Pharmaceutical's HS-10340, and Haizheng Pharmaceutical's HS-236 have not updated their clinical progress for more than 3 years.

In the face of the "stillness" of the industry, Heyu Pharmaceutical (02256) is constantly "breaking the ice" with ABSK011, and after a series of reshuffle, ABSK011 has quietly stood in the first order of clinical progress, which shows its profound research and development skills.

In fact, the indication of ABSK011 is liver cancer with a large number of patients and high mortality. Data show that there are about 906000 new liver cancer patients in the world every year, ranking sixth in malignant tumors and 830000 deaths, ranking third in malignant tumors. The incidence of liver cancer is particularly high in China. There are 410000 new cases of liver cancer and 391000 deaths in China every year, accounting for nearly half of the global morbidity and deaths. According to statistics, the number of patients with FGF19/FGFR4 overexpression accounts for about 30% of the total number of liver cancer patients in the world, but no targeted therapy for FGFR4 has been approved.

Zhitong Financial and Economic APP learned that the current treatment plan for liver cancer is mainly local treatment ±systematic antineoplastic drug therapy. Systemic therapeutic drugs are mainly anti-angiogenic targeted drugs and immune checkpoint inhibition. Although considerable progress has been made, there is still a lack of accurate, efficient and safe treatment. From the beginning of the project, ABSK011 hopes to conquer this cancer by virtue of its excellent R & D strength.

With the hope of the whole industry, Heyue Medicine described the preclinical drug resistance mechanism of FGFR4 inhibitors in EGFR inhibition overcomes resistance to FGFR4 inhibition and potentiates FGFR4 inhibitor therapy in hepatocellular carcinoma published in September in Molecular Cancer Therapeutics, a well-known journal of the American Cancer Research Society (AACR). It was found for the first time that EGFR activation is one of the main mechanisms leading to FGFR4 inhibitors' drug resistance in liver cancer. And further revealed the great potential of EGFR and FGFR4 inhibitors combined therapy "transformation research results.

This paper not only attracts the international medical community to pay attention to the FGFR inhibitor again, but also points out a new direction for the clinical development of the inhibitor in the words of industry experts.

The discussion has not subsided, and recently, Heyu Medicine announced the clinical data of ABSK011, a drug used to treat FGF19+HCC, at the ESMO conference. Data displayIn terms of effectiveness, the ABSK011 BID cohort had an ORR of 40.7% in patients with FGF19 overexpression and 70.4% in patients with hepatocellular carcinoma. In the treatment of FGF19+HCC patients, it showed good safety, and there was no case of dose-limiting toxicity (DLT) event.

The ORR is 40.7%, the DCR is 70.4%, and it is safe and non-toxic, which is a complete "cracking" progress and breakthrough. You should know that when the objective remission rate of the domestic standard second-line antivascular targeting drugs repagofinib and apatinib is only 11%, and the immunotherapeutic drugs Pabolizumab, Carrelizumab and tirelizumab are only 13%, 15% and 13%, Hexue Pharmaceutical's ABSK011 shows the potential to break the deadlock in the second-line treatment of liver cancer and explore more frontline patients.

In addition to announcing ABSK011's excellent data progress, Heyu also presented the first human trial clinical data of oral small molecule PD-L1 inhibitor ABSK043 in patients with advanced solid tumors at the ESMO conference.

According to Zhitong Financial APP, ABSK043 is a small molecular PD-L1 inhibitor with good oral bioavailability and high selectivity, and is being developed for the treatment of various cancers and potential non-tumor indications. Although anti-PD-1/ and anti-PD-L1 antibodies have completely changed the treatment of cancer, antibody-based immunotherapy has many defects, such as lack of oral bioavailability, blood-brain barrier permeability and immunogenicity, inability to enter some solid tumors effectively, these defects may be improved by small molecule inhibitors.

Up to now, a number of PD-1/PD-L1 antibody drugs have been approved and put on the market all over the world, but at present, ICI therapy is mainly monoclonal antibody drugs, and its high treatment cost often deters many patients. Compared with monoclonal antibodiesIn addition to being more convenient for oral administration, small molecular inhibitors also have the advantages of short half-life, simple preparation process, low price, effective penetration of blood-brain barrier and easier access to tumor microenvironment.Unfortunately, no small molecular PD-L1 inhibitors have been approved on the market.

In the face of the blue sea of the market, Heyu Medicine is obviously seizing the opportunity quickly. In September 2021, the company completed the first patient administration of ABSK043's Phase 1 clinical trial in Australia and obtained domestic clinical approval in 2022.

From the clinical data of ABSK043 announced at the ESMO meeting, PD-L1 small molecules do have strong potential. In the study, the preliminary anti-tumor activity of ABSK043 has been observed, and the dose has climbed to 1000 mg BID. At present, it is well tolerated, no dose-limiting toxicity events have been reported, and has the same safety characteristics as monoclonal antibody immune checkpoint inhibitors. The PD effect related to the target was consistent with the inhibition of PD-L1, and also consistent with the reported data of PD- (L) 1 monoclonal antibody.

Of course, in addition to the two latest research results, this year can be said to be a fruitful year for Hechong Pharmaceuticals, and the clinical progress of its core products ABSK021, ABSK091 and other clinical pipeline products in the middle and later stage is also making steady progress, which is about to realize the commercial value realization period.

In contrast, the cash value of Heyu Medicine itself is also further highlighted. Leerink Research said that at a 15 per cent discount rate and 5X valuation, the company's current reasonable market capitalization is at least HK $11.537 billion, or HK $16 per share, which is nearly 10 times its current market capitalization, and gives an OP (bullish) rating.

To sum up, considering the already strong R & D strength and the background of continuous cashing of products, the market will obviously reevaluate the value of Heyu Medicine and fill in the last value depression of Biotech.