In recent years, the research and development of ADC drugs has been hot, and many domestic and foreign pharmaceutical companies have laid out the ADC track, in order to gain a share in this field. Antibody–Drug Conjugates (ADC) are composed of monoclonal antibody drugs targeting specific antigens and small molecule cytotoxic drugs coupled through linkers, which have both the powerful killing effect of traditional small molecule chemotherapy and antibody drugs. tumor targeting. From the focus of disease areas, the concentration of ADC drugs is very high, mainly in the field of tumors. In fact, the first ADC drug was approved for marketing in 2000, and subsequent ADCs were tepid in the industry. Until 2019 and 2020, the outbreak period of ADC approval began. The FDA has successively approved 5 ADC drugs (Polivy, Padcev, Enhertu). , Blenrep and Trodelvy).

01

ADC drug structure and mechanism of action

The three major components of ADC drugs include: human monoclonal antibodies, cleavable/non-cleavable linkers, and small molecule chemotherapeutics/cytotoxic drugs. Monoclonal antibodies and cytotoxic drugs are coupled through linkers. In simple terms, ADC drugs are formed by combining monoclonal antibodies with highly cytotoxic chemotherapeutic drugs through linkers.

The mechanism of ADC action is simple and clear. After the ADC drug enters the body, the antibody part specifically binds to the target cells expressing tumor antigens. After the ADC drug is endocytosed by tumor cells, it enters the lysosome for degradation. The highly effective active form is released in sufficient amount to complete the killing of tumor cells. Simply put, after the ADC drug enters the interior of tumor cells, it destroys tumor cell DNA, inhibits tumor cell division, and kills tumor cells.

02

Domestic ADC drug leader

Rongchang Bio-Pharmaceutical (Yantai) Co., Ltd. was founded in 2008 and is headquartered in Yantai Economic and Technological Development Zone, China (Shandong) Pilot Free Trade Zone, with R&D centers and branches in Beijing, Shanghai, San Francisco and Washington. , was co-founded in 2008 by Rongchang Pharmaceutical and Professor Fang Jianmin, a scientist studying in the United States. On November 9, 2020, Rongchang Bio was listed on the Hong Kong Stock Exchange, raising a total of US$590 million, setting a record for the world's largest biotech IPO that year. On January 11, 2022, the China Securities Regulatory Commission announced that it has approved the registration and issuance of Rongchang Bioscience and Technology Innovation Board. The IPO plans to raise 4 billion yuan.

The first new ADC drug was approved:

HER2 is an important biomarker that is ubiquitously expressed in many different tissues, and its overexpression has been implicated as a genetic driver of multiple cancer types. In recent years, HER2 has become one of the main targets for the development of ADCs by global pharmaceutical companies. HER2-positive/highly expressing BCs (IHC 2+/FISH+ or IHC 3+) continue to be extensively studied and are the only approved anti-HER2 ADCs. The type of cancer being treated. However, variable levels of HER2 expression (including low expression of ), low-to-moderate HER2 expression (IHC 2+/FISH- or IHC 1+) was observed in nearly 50% of BC (breast cancer) cases, thus suggesting that anti-HER2-ADCs also have a role in HER2-high BC Great therapeutic potential and opportunity.

Vidicitumumab (R&D code: RC48): an anti-HER2 antibody conjugated drug independently developed by Rongchang Bio, and the first ADC independently developed by a Chinese company. Its molecular structure includes a novel humanized HER2 antibody; its linker is cleavable in tumor cells; its small-molecule cytotoxic drugs have high toxicity and bystander killing effects.

On June 9, 2021, China's National Medical Products Administration (NMPA) announced that it has passed the priority review and approval process with conditional approval of vedicitumab for injection (trade name: Aidixi) Treatment of patients with HER2-overexpressing locally advanced or metastatic gastric cancer, including gastroesophageal junction adenocarcinoma, treated with 2 systemic chemotherapy. Data from a phase 2 registrational clinical trial showed that the objective response rate (ORR) was 24.4%, the median progression-free survival (PFS) was 4.1 months, and the overall survival was 4.1 months in patients with the above indications. The median duration (OS) was 7.6 months.

In early July 2021, Vidicitumab was officially launched nationwide. According to the data of Yaorong Cloud (www.pharnexcloud.com), the price of this product before entering the medical insurance negotiation is 60mg/support/box corresponding to 13,500 yuan/box. After entering the medical insurance catalog, it is 3800 yuan/box. At the 2022 JPM conference, Rongchang Biotech stated that the sales team of this HER2-ADC currently has 200 people, covering 400 hospitals and 405 pharmacies in 130 cities in 30 provinces.

On January 5, 2022, Rongchang Bio announced that the new indication of Vidicitumab for injection (trade name: Aidexi®) has been approved by the National Medical Products Administration (NMPA) for the treatment of patients with previously Patients with locally advanced or metastatic urothelial carcinoma who have undergone platinum-based chemotherapy and have overexpressed HER2, i.e., immunohistochemical findings of 2+ or 3+. The indication was submitted for approval on July 14, 2021, and it took 5 months to be approved quickly, becoming the first ADC drug targeting HER2 in the treatment of urothelial cancer in China.

Epidemiological data show that urothelial carcinoma is one of the common malignant tumors, and its morbidity and mortality are the first among male genitourinary tumors. According to the Sullivan report, the number of new cases of urothelial cancer in the world will reach about 662,000 in 2030, with a compound annual growth rate of 2.5% from 2025 to 2030; in China, the incidence rate of urothelial cancer is growing faster than At the global level, it is expected to reach about 106,000 cases in 2030. Statistics show that the recurrence and metastasis rates of the disease are relatively high. About 20% of patients have already metastasized or progressed to an unresectable stage at the time of diagnosis. The existing treatment methods are far from meeting the huge clinical needs.

It is worth noting that Rongchang Bio has reached an exclusive global license agreement with the internationally renowned biopharmaceutical company Seagen Inc. NASDAQ: SGEN in August 2021: for Rongchang Bio’s new ADC drug Vidicitumab Antibiotic (RC48, trade name: Aidixi), Seagen will pay an upfront payment of $200 million + up to $2.4 billion in milestone payments to obtain development and commercialization rights to the drug in parts of the world. A $200 million down payment has been received so far.

03

ADC domestic layout enterprise

According to Pharnexcloud data (www.pharnexcloud.com), domestic companies developing ADC drugs include: Hengrui Medicine, Rongchang Bio, Hansoh Pharmaceutical, CSPC, CStone Pharmaceuticals, Yilian Bio, Bio-Tech, Bailix Kang, Boan Bio, Baili Pharmaceutical, Wuxi Zhikang Hongyi Bio, Kai Tak Pharmaceutical, Anwita Biosciences, Innovia, Yin En Bio, Adcentrx Therapeutics, New Code Bio, Doxi Bio, Kelun Pharmaceutical Industry, BeiGene, Yehui Pharmaceutical, Antengene, Conway Bio, Shijian Bio, Yingshi Bio, Qilu Pharmaceutical, Meyake/Lepu Bio, Dashi Pharmaceutical, Tianguangshi, Pufang Bio ( ProfoundBio), Shangjian Bio, Livzon Bio, Guangzhou Lupeng Pharmaceutical, Heyuan Addis, Baohe Ante Bio, Nuo Ling Bio, Junshi Bio, Dong Yao Pharmaceutical, Shanghai Pharmaceutical, Fudan Zhangjiang, Jiahe Bio, New Idea, Lixin Medicine, Cumming Bioall, Tasly Bio, Lianning (Suzhou) Bio, Henlius, Tris/Zhenbao Island, Hisun Pharmaceutical, Sunshine Guojian, Takata Bio, Kangyuan Jiuyuan, Genting Xinyao, Hangzhou Acres, Boaoxin Biology, Puzhong Discovery, etc.

There are more than 120 ADC drug R&D pipelines in China, and nearly 70 R&D companies

04

ADC Oncology Market Forecast

In the 2021 Nature Reviews Drug Discovery, "The oncology market for antibody-drug conjugates", it is estimated that in 2026, the global sales of currently listed ADCs will exceed US$16.4 billion; among them, Enhertu may become the highest sales volume with US$6.2 billion. ADC; while T-DM1 sales will be $2.3 billion. Enfortumab vedotin, approved for previously treated metastatic urothelial carcinoma, is expected to generate $3.5 billion in global sales in 2026. The popular Trop-2 drug, Sacituzumab-govitecan, is expected to be worth $1.1 billion for breast and urothelial cancers, among others.