ADC drugs are mainly used in the field of anti-tumor, which is one of the hot research directions in recent years.
ADC is composed of three parts: monoclonal antibody (mAb), coupling chain (linker) and cytotoxic small molecule (cytotoxin/payload). tumor lesions.
Compared with traditional chemical drugs and biological drugs, the safety and effectiveness are significantly improved. The ADC field has made great progress in the past 10 years, and the therapeutic window has continued to expand. According to the forecast of Evaluate Pharma and BCG, the global ADC market is expected to reach US$12.9 billion in 2024, with a compound annual growth rate of about 35% from 2018 to 2024.
01 Global ADC drugs and market analysis
In the past year, foreign antibody-conjugated drugs (ADCs) have been hot spots. In September last year, Gilead acquired the ADC company Immunomedics at a premium of 108% and a total value of 21 billion US dollars, triggering an acquisition no less than 11.9 billion US dollars that year. KITE is highly concerned by the industry. Recently, Pfizer has transferred two ADC candidate products to Pyxis.
Currently, a total of 11 ADC drugs have been approved globally, including Mylotarg (Pfizer), Adcetris (Seattle Genetics/Takeda), Kadcyla (Roche), Besponsa (Pfizer), Lumoxiti (AstraZeneca), Polivy (Roche), Padcev (Seattle Genetics / Astellas / Merck), Enhertu (AstraZeneca / Daiichi Sankyo), Trodelvy (Immunomedics), Blenrep (GSK), Akalux (Rakuten Aspyrian).
From the perspective of R&D companies that have listed drugs, Pfizer, Seattle Genetics, Roche and AstraZeneca each have 2 models, and the other 3 companies have 1 model each.
Pfizer's Mylotarg is the earliest approved ADC drug, approved by the FDA in May 2000 for the treatment of patients over 60 years of age with first relapsed CD33-positive acute myeloid leukemia (AML), but Mylotarg has not shown significant clinical benefit based on late stage And there are certain safety issues. In 2010, Pfizer delisted Mylotarg until September 2017 before listing it again in the United States. In June 2020, the drug expanded its indications to newly diagnosed CD33-positive AML patients aged ≥1 month.
Kadcyla and Adcetris have gradually grown into "blockbuster" drugs, both breaking the $1 billion mark in 2019, reaching $1.081 billion and $1.572 billion, respectively. Kadcyla has become the international second-line standard treatment for HER2-positive breast cancer. In May 2019, Kadcyla was also approved by the FDA as an adjuvant treatment for patients with HER2-positive early breast cancer, further expanding the market space.
At present, the two drugs have been approved for marketing in China in January and May 2020, respectively, and Kadcyla (Hercele) has been included in the 2020 medical insurance catalog.
As third-generation ADCs, Enhertu and Trodelvy have strong momentum. The indication of Enhertu approved in December 2019 is HER2-positive breast cancer. Given its large patient population, the drug has a huge market prospect. At the same time, in January this year, Enhertu further expanded its indications, and the FDA approved it for the treatment of HER2-positive breast cancer. Patients with locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma. According to AstraZeneca's annual report, Enhertu will become the new standard in breast cancer, with sales of $200 million in its first year.
Trodelvy, approved in May 2020, is the world's first TROP-2-targeted antibody-drug conjugate therapy, and the first drug launched by Immunomedics since its establishment 37 years ago. Net sales of $20.1 million. SGEN tried to acquire Immunomedics for $2 billion but failed, and finally let Gilead start.
In September 2020, Gilead acquired Immunomedics at a premium of 108% and a total value of $21 billion, and also included Trodelvy in the bag. Industry analysts have previously stated that the peak sales of Trodelvy after its listing is expected to reach more than 1 billion US dollars, and Gilead's buy-buy-buy strategy has won a big cake for it on the ADC plate.
The launch meeting was held by Medicilon and DAC Biotech of the contract research on ADC preclinical study
Antibody-Drug Conjugate(ADC) Platform
Medicilon Assists - The first China-made targeting folic acid receptor FRα ADC injection BAT8006 was approved for clinical use
In addition, several other ADC drugs that have been launched in recent years have not achieved high volume, but according to Clarivate Analytics, there will be several annual sales of more than 1 billion US dollars by 2024, including Polivy and Enhertu.
In addition to the 11 ADCs already on the market, according to ClinicalTrials.gov data, as of March 19 this year, a total of 155 ADC drug clinical trials are underway around the world, and they are still growing. Constantly have to expand their ADC pipeline.
In November 2020, Merck acquired VelosBio for $2.75 billion, and in December Boehringer Ingelheim acquired NBE Therapeutics for 1.18 billion euros. In addition, Sterling announced plans to fully acquire ADC Biotechnology in the UK in the first quarter of 2021.
02 Major domestic ADC drugs and R&D companies
In China, thanks to the continuous improvement of the domestic innovative drug research and development level, domestic companies have also quickly followed up in ADC drug research and development.
Among them, Remegen's HER2 ADC drug RC48 has been officially accepted by the State Food and Drug Administration, and it is the fastest self-developed ADC drug in China; in addition, there are more than 20 ADC drugs in different stages of clinical trials under development, including Many companies such as TOT BIOPHARM, Hengrui Medicine, Kelun Pharmaceutical, Genting Xinyao, Bio-Tech, and Zhejiang Medicine have products that have entered the clinical stage.
In addition to most targets targeting HER2, others include c-Met, EGFR, Trop-2, CD20, BCMA, and others.
Domestic ADC drug research and development (Yigu tabulation) picture❖Remegen-Vidicitumab
Vidicitumumab (trade name: Aidixi®, research code: RC48) was developed by Remegen and is the first self-developed antibody-drug conjugate (ADC) drug to submit a new drug marketing application in China. It targets the HER2 protein on the tumor surface, can accurately identify and bind to cancer cells, penetrate the cell membrane and enter its interior, thereby killing cancer cells. The drug became the first ADC drug approved for clinical research in 2015.
On August 27, 2020, the State Food and Drug Administration has officially accepted the new drug marketing application of the drug for the treatment of patients with locally advanced or metastatic gastric cancer (including gastroesophageal junction adenocarcinoma), and has been included in the priority review and approval process. Acceptance No. : CXSS2000044 country. In addition, Vidicitumab (RC48) was also granted Breakthrough Therapy Designation by the U.S. FDA in September 2020 for the treatment of urothelial carcinoma.
❖TOT BIOPHARM TAA013
TAA013 is an ADC drug under investigation containing trastuzumab and maytansine derivative (trastuzumab-MCC-DM1) developed by TOT. By virtue of the targeting of trastuzumab, the drug binds to specific antigens on the tumor cell membrane, induces endocytosis, and allows the highly active cytotoxic drug DM1 to enter cells, thereby inducing apoptosis, and is used for the treatment of HER2-positive breast cancer. cancer patients.
The Phase III clinical study of TAA013 is currently underway, a multicenter, randomized, parallel-controlled, open-label study in patients with unresectable locally advanced or metastatic HER2-positive breast cancer who have failed trastuzumab therapy , to compare the efficacy and safety of lapatinib combined with capecitabine, so as to further verify the efficacy and safety of TAA013.
❖Hengrui Medicine SHR-A1811
As a leading domestic innovative drug research and development company, Hengrui Medicine also has a deep layout in the ADC field. At present, the company's ADC drug SHR-A1403 targeting c-MET, as well as SHR-A1201 and SHR-A1811 targeting HER2 are in clinical stage. In January this year, the clinical trial application of Hengrui Medicine's fourth ADC drug SHR-A1904 was also accepted by the State Food and Drug Administration.
SHR-A1811 for injection is a HER2-targeted antibody-drug conjugate (ADC) independently developed by Hengrui Medicine. It can bind to the cell membrane surface of HER2-expressing cells, and then be endocytosed into cells to reach lysosomes to release small molecules. Molecular toxins, which ultimately induce tumor cell apoptosis, have both the high targeting of antibodies and the powerful killing power of cytotoxic drugs on target cells.
❖Kelun Pharmaceutical SKB264
On April 8, 2020, the official website of CDE showed that SKB264, a class 1 new drug for injection of Sichuan Kelun Botai Biopharmaceutical Co., Ltd., received an implied clinical license and is intended to be used for the treatment of solid tumors.
SKB264 for injection is an ADC drug targeting human trophoblast cell surface antigen 2 (TROP-2), which is highly expressed in a variety of epithelial tumors. Its coupling method and toxin small molecule have independent intellectual property rights, and it is intended for the treatment of malignant tumors.
SKB264 for injection achieves high toxin load through a new coupling method, the process is stable and controllable, easy to scale up, and the product has good batch-to-batch consistency.
On August 23 this year, KLUS PHARMA INC, a subsidiary of Kelun Pharmaceutical Holdings, received a written notice issued by the FDA to allow its "SKB264 for injection" antibody conjugated drug (ADC) to conduct clinical trials in the United States. Up to now, Kelun Pharmaceutical has invested about 25 million yuan in research and development expenses on the drug.
In addition, Kelun Pharmaceutical's ADC drug also has A166 targeting HER2, which has submitted a key phase II application to CDE; the ADC drug targeting Claudin18.2 will enter the clinic in 2021.
❖CSPC SYS1801
The Claudin18.2-targeted ADC drug SYS1801 independently developed by CSPC is the first Claudin18.2-targeted ADC drug by a domestic pharmaceutical company. On November 26, 2020, the drug is used for the treatment of gastric cancer (including gastroesophageal junction cancer) The indications have been granted orphan drug designation by the FDA.
In addition, on July 25, 2019, CSPC's recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugated drug injection (DP303c) was approved for clinical use, and the indication is: advanced Her2-positive breast cancer.
❖Miracogen MRG003
The company currently has three self-developed innovative ADC drugs, MRG003, MRG002, and MRG001, which have obtained clinical approval from NMPA, and three phase I clinical studies are in progress.
❖Dacbiotech DX126-262
The new-generation ADC drug DX126-262 (DAC-001) developed by the company has been approved for clinical trials by the State Food and Drug Administration for the treatment of Her2 breast cancer and gastric cancer. U.S. clinical submissions are in progress.
❖Teruisipharm TRS005
TRS005, an ADC drug independently developed by Tris, is used for relapsed and refractory non-Hodgkin's lymphoma. In May 2018, TRS005 for injection was approved for clinical use, and phase I clinical research has been started, and it is planned to be used for relapsed and refractory non-Hodgkin's lymphoma. Non-Hodgkin's Lymphoma.
TRS005 is a national class 1 innovative drug, which has received rolling support from the National Twelfth Five-Year Plan and the Thirteenth Five-Year Plan for "Major New Drug Creation", and has applied for three Chinese patents and one PCT international patent. TRS005 has demonstrated excellent tumor inhibition in preclinical animal tumor models, and its efficacy is more than 8 times that of blockbuster monoclonal antibody drugs.
Whether at home or abroad, the ADC drug research and development track is hot, and its market space is huge. According to a research report released by CICC, the entire ADC drug market is expected to exceed $50 billion. It remains to be seen who can come out on top in this track.
评论
发表评论