Recently,About Trop2 ADCProgress in drug development continues to be made.February 22,The official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) announced,Trop-2 ADC Independently Developed by Qide Medical TechnologyDrugGQ1010 Injection Submitted for Clinical Trial.Recently,On February 19, AstraZeneca and Daiichi Sankyo announced a new Trop2 ADC drugDatopotamab Deruxtecan for the Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer Previously Treated with Systemic TherapyMarketing application accepted by FDA。If successfully approved, this product will become the world's first Trop2-targeted ADC for lung cancer treatment.
Introduction to Trop2 ADC Drug Targets
As a novel antibody drug,The热度 of ADC has been increasing from 2023 to 2024, showing no signs of slowing down.Looking at the current R&D pipeline layout of ADC drugs, the top three ADC drug targets in China are：HER2、TROP2、Claudin18.2，Following the classic popular target HER2, Trop-2 has become the second hotspot of interest for companies as a target without any ADC products currently on the market in China.。Trophoblast cell surface antigen 2 (Trop2), also known as Tumor-associated calcium signal transducer 2 (TACSTD2), is one of the members of the TACSTD protein family. It consists of a hydrophobic leader peptide, an extracellular domain, a transmembrane domain, a cytoplasmic tail, and the cytoplasmic tail contains a highly conserved PIP2 binding sequence, tyrosine, and serine phosphorylation sites.It is a cell surface glycoprotein that transmits intracellular calcium signals and extracellular signaling pathways, playing a crucial role in tumor cell proliferation, apoptosis, and invasion, thereby influencing the prognosis and treatment of cancer patients.Trop2By mediating E-cadherinThe downregulation of n leads to epithelial-mesenchymal transition (EMT), thereby preventing apoptosis and senescence, and promoting the invasion and metastasis of tumor cells.Global Trop2 ADC Market SizeTrop2 is highly expressed in a variety of malignant tumors such as gastric cancer, pancreatic cancer, ovarian cancer, colon cancer, prostate cancer, etc. It is a pan-cancer target with huge market potential.。
According to Frost & Sullivan's forecast,Global Trop2 ADC MarketThe scale is expected to reach 700 million US dollars in 2022Grow to USD 25.9 billion by 2030, with a compound annual growth rate of 57.6%.。
China Trop2 ADC MarketExpected to reach 200 million yuan by 2023Increase to 23.6 billion yuan before 2030,The annual compound growth rate is 103.0%.。
In terms of revenue from marketed products, currently, only one TROP2 ADC drug, Trodelvy from Gilead, has been approved globally, with a global income of $680 million in 2022.
Global Trop2 ADC Drug Development ProgressAs long as it's细分 enough, it will always be the best. BiopharmaceuticalsThe TROP2 ADC Sub-sectorIt is the same.According to the incomplete compilation by the Yaoyan Network team,Currently, there are 19 pipelines globally that have entered clinical stages or above, among which 1 has been approved for marketing, 2 are under marketing application, 1 has entered Phase III clinical trials, and the rest are in Phase I or Phase I/II.Swipe up on the image to view moreCurrently,Global Trop2-Targeted Drugs MarketOnly oneTrop2-Targeted Drugs Launched，That is, sacituzumab govitecan developed by Immunomedics, a subsidiary of Gilead.It has been approved in the United States for three indications: advanced TNBC (3L+), advanced UC (2L), and HR+/HER2-BC (3L+). In June 2022, it was approved by the National Medical Products Administration for marketing in China to treat unresectable advanced metastatic TNBC (3L+).And the current progress is at the forefrontTrop2 ADC DrugThere are 2 pipelines., respectively DS-1062 from Daiichi-Sankyo/AstraZeneca and SKB264 from the Chinese company Kelun-Biotech.Fig.|Trodelvy Structure (SourceHuaan Securities）
AstraZeneca/Daiichi Sankyo: DS-1062
DS-1062YesThe Trop2 ADC Drug with the Fastest Progress。DS-1062 is one of the three core DXd antibody-drug conjugates (ADCs) in Daiichi Sankyo's oncology pipeline.On February 19, AstraZeneca and Daiichi Sankyo announced the new Trop2 ADC drug DS-1062FDA Accepts Application for Datopotamab Deruxtecan to Treat Advanced Non-Squamous Non-Small Cell Lung Cancer Patients Who Have Undergone Systemic Therapy. If approved, this product will become the world’s first Trop2-targeted ADC for lung cancer treatment.The marketing authorization application is primarily based on the positive data from the pivotal Phase III TROPION-Lung01 study.An ongoing global, randomized, multicenter, open-label Phase 3 trial，Efficacy and safety of Dato-DXd (6.0mg/kg) compared with Docetaxel were evaluated in patients with locally advanced or metastatic NSCLC who had received at least one prior therapy and had no targetable genetic mutations.The dual primary endpoints are progression-free survival (PFS) and overall survival (OS) as assessed by blinded independent central review (BICR).
The results showed that, compared with the current standard treatment docetaxel, Dato-DXd demonstrated a statistically significant and clinically meaningful improvement in one of the primary endpoints, progression-free survival (PFS).In addition, Dato-DXd inAnother Primary EndpointIn terms of overall survival (OS), an advantage was also demonstrated, although it did not reach statistical significance. The median OS for the two groups was 12.4 months and 11.0 months, respectively.Particularly in the subgroup of patients with non-squamous histology, Dato-DXd demonstrated a clinically meaningful PFS benefit and a numerically favorable OS trend. Additionally, Dato-DXd showed a good safety profile, with the most common adverse events being stomatitis and nausea.SKB264 is the core ADC product of Kelun Biotech., with a high DAR value (7.4), the toxin selects a novel pyrrolobenzodiazepine-derived topoisomerase I (TOPO1) inhibitor, which has moderate cytotoxicity. The proprietary Kthiol design strategy uses a new carbonate linker to selectively release cytotoxic payloads into tumor tissue by leveraging the acidic tumor microenvironment.Preliminary clinical data from its global Phase 1/2 trial showed,SKB264 has demonstrated encouraging efficacy and potentially favorable safety in various types of heavily pretreated advanced solid tumors. SKB264 has currently been granted three Breakthrough Therapy Designations by the CDE for triple-negative breast cancer, EGFR-mutant non-small cell lung cancer, and HR+HER2- breast cancer.SKB264's differentiated molecular design is highly competitive:Compared with Trodelvy：Due to the irreversible linker-mAb conjugation and differentiated payload structure, the plasma stability of SKB264 has been improved.Comparison of DS-1062：Due to the stronger hydrophilicity of the CL2A linker, SKB264 still maintains good ADC hydrophilicity even with a higher DAR value. The risk of ILD toxicity associated with SKB264 and KL610023 is minimal.On December 9, 2023, the marketing application for SKB264 (MK-2870) in treating triple-negative breast cancer has been accepted by the NMPA and is expected to become the first domestically produced Trop2 ADC drug in China.
Applied for clinical trials todayGQ1010 Injection isIndependently Developed by Qide Medical TechnologyTrop-2 ADC Drug.
GQ1010Is based onQide PharmaceuticalA novel Trop2-targeted ADC drug developed with unique iLDC technology, cleavable "open-loop" linkers, and a new topoisomerase I inhibitor.
Figure | Qide Medical Technology Pipeline (Source: Official Website)Preclinical studies have shown, GQ1010 demonstrated stronger in vitro cytotoxicity and bystander killing effects than DS1062 across various Trop2+ cancer cell lines.Strong in vivo anti-tumor activity was further demonstrated across different CDX models, including TNBC, gastric cancer, head and neck (H&N), and pancreatic cancer, with efficacy superior to DS1062 and Trodvy, consistent with in vitro data.Compared with similar competing products, GQ1010 has demonstrated highly differentiated preclinical characteristics, with superior stability, safety, and efficacy, and is expected to become a First-in-class drug.In April 2023, Qide Medical Technology (Suzhou) Co., Ltd. exclusively licensed the global development and commercialization rights of GQ1010 (excluding Greater China: mainland China, Hong Kong, Macao, and Taiwan) to Pyramid, receiving an upfront payment of $20 million, potential milestone payments of up to $1 billion, and tiered royalties based on net sales.
Figure | Qide Medical Technology Pipeline (Source: Official Website)References:
1. Qide Medical Technology(Suzhou)Co., Ltd. Official Website
2. Deutsche Bank Securities Research, Huatai Securities
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