ADC research and development pipeline explosion non-cancer indications will become the next "blue sea"?

The ADC, a therapeutic model that targets antibodies to specific antigens, is known as a "magic bullet" that can accurately target tumor cells by connecting the linker to the drug payload.the idea was proposed as early as 1913, the first ADC was not approved by the FDA until 2000, and the development of the ADC has not been smooth since then.But as scientists continue to work, four innovative ADCs have been approved by the FDA in the past two years, doubling the number of ADCs approved.there are also many innovative therapies in the research and development pipeline, and the number of adaptive syds in the treatment has increased significantly., the treatment of ADC diseases has begun to develop in non-cancer areas, and the load of non-cytotoxic drugs is frequent in early research and development projects.Today, the pharmaceutical Mingkant content team will take stock of the research and development pipeline of this innovative treatment model in conjunction with public information.The U.S. and China approved antibody conjugate drug timeline (drug Mingcond content team mapping, data as of July 24, 2020) Oncology antibody conjugate drugs: long-term technical accumulation of the concept of antibody coupling drugs (ADC) is not difficult to understand, targeting specific antigens monoclonal antibodies by connecting to the binding strain and cell toxicity drugs and other loads, so that the load can only work in the expression of antigen-specific cells.the initial goal of this treatment model is to connect cytotoxic drugs with monoclonal antibodies that target blood tumors or solid tumors, and accurately target killer tumor cells.However, the development process to realize this concept requires the overcoming of a number of obstacles.ADCs to achieve safety, effectiveness, the specificity of monoclonal antibodies, the toxicity of cytotoxic loads, the stability of the connectors, and the number of loads that can be coupled to antibody molecules all put forward high requirements.early development of ADCs due to these technologies can not be perfected, resulting in a narrow drug treatment window.'s first approved ADC was also withdrawn due to toxic side effects.However, as scientists continue to work hard, ADC design technology is maturing.from the research and development pipeline in the research project can be seen, ADC's in-the-form indications since 2011, the explosive growth.the number of ADCs in the study of indications in the last 20 years (data source: Cortellis, non-radioactive-free drugs, the same drug may be used to treat multiple indications, as of July 14, 2020) From the clinical development stage, the growth of indications appears in the development phase of the research and development pipeline.by development phase, there are currently several in-therapy in Phase 1 clinical trials and Phase 2 clinical trials, which means that The ADC is the treatment model that is expected to continue to produce innovative therapies in the future. Another reason for the explosive growth ofADC research and development pipeline by development stage (data source: Cortellis, discovery phase: in vitro experimental phase; pre-clinical: in vivo animal experiment; drug Mingcond content team mapping) indications growth is that the same ADC can be used to treat multiple indications due to the maturity of ADC technology. One example ofis Enhertu, an antibody conjugate drug aimed at HER2, jointly developed by Astra Zeneca and Daiichi Sankyo, which was approved last year., the ADC, which has been approved for her2-positive breast cancer, has also had a welcome effect in the treatment of non-small cell lung cancer (NSCLC), stomach cancer, and colorectal cancer.AstraZeneca and I3 also plan to explore enhertu's effects in patients with low-expression breast cancer in HER2, as well as in patients with HER2-expressed non-limited cancer.these explorations need to be backed by a balance between the good efficacy and safety of this innovative ADC, allowing researchers to try HER2 expression cells with fewer cells, or HER2 expression low levels of cancer indications.The Expansion of Enhertu (DS-8201) by AstraZeneca (Picture: First Three Co., A.I.M.) this year' antibody-conjugated drug Trodelvy, which was approved this year, is also used in different clinical trials to treat other types of cancer, such as peepathic skin cancer, NSCLC, head and neck cancer, liver cell cancer, etc.non-cancer indications become the next "blue sea" of ADC At present, most aDC stoicisms in the clinical development stage are solid tumors or blood tumors, however, the maturity of ADC design technology has led many biomedicine and technology companies to explore the use of ADC to treat non-oncology indications, including ophthalmology, immunology, anti-infection, endocrine/metabolic disease areas.most of these treatments for non-cancer-adapted aDCs are still in the early stages of development, but their proportion in early development is significantly higher than in clinical development.this trend suggests that non-cancer indications could be the next "blue sea" of ADC drug development.the proportion of non-cancer indications and cancer indications at different stages of development (data source: Cortellis, discovery stage: in vitro experimental stage; pre-clinical: in vivo animal experiment; drug-based Conde content team mapping) In the treatment of these non-cancer areas, the pharmaco-linked drug load on the ADC is no longer limited to cytotoxic drugs.according to incomplete statistics, in the treatment of non-cancer indications, the vast majority of the load is non-cytotoxin drugs, accounting for 90% of research and development projects.these non-cytotoxic drug loads include immunomodulators, enzymes, and innovative treatment models such as antisense oligonucleotides and siRNA., for example, Adity last year partnered with Lilly to develop innovative treatments for immunological diseases using the company's antibody-conjugated oligonucleotide technology platform.using antibody coupling technology, oligonucleotide drugs can be delivered to more types of tissue shipping and the toxic side effects of using lipids to deliver oligonucleotides can be avoided. The ABBV-3373, developed byAbbVie, is in Phase 2 clinical development.this is an ADC that is a combination of antibodies that target TNF and glucocorticoid receptor regulators (Glucocoticoid Receptor Modulator, GRM).it can avoid systemic side effects of corticosteroids while regulating local inflammatory responses. it has shown welcome clinical activity in Phase 2a clinical trials for patients with rheumatoid arthritis. the results of this proof-of-concept study to support AbbVie's further development of the TNF-based ADC technology platform, which will be tested in clinical trials to test the effectiveness of this platform for other inflammatory diseases. concluded antibody conjugate dyser has experienced a tortuous path in the early stages of development, and in recent years, both in terms of the number of approved therapies and from the rate of expansion of therapy and indications, have shown an explosive growth trend. and carrying non-cytotoxic drug loads, the proportion of ADCs in the early stages of the development pipeline is increasing, demonstrating the potential of ADCs as a new treatment model for diseases other than cancer. in China, more than 20 Chinese biopharmaceutical companies have invested in the development of ADC, including Collon Pharmaceuticals, Hangzhou Polyju, Dongyu Pharmaceuticals, Hengrui Pharmaceuticals, Stone Pharmaceutical Group and other companies. most of the drugs developed by Chinese enterprises in the research ADC are still in the stage of clinical development and pre-clinical development in Phase 1/2. drug Mingcon content team mapping (data source: Cortellis, discovery stage: in vitro experiments; pre-clinical: in vivo animal experiments) Related reading: 3 ADC drugs approved in a year, "bio-missile" research and development to meet the climax, has covered four major cancer species! We look forward to the smooth progress of the ADC candidate therapy in the development and an early development of innovative treatment options that change the lives of patients. References: s1 How The Next Generation Antibody Drug Conjugates Expands Beyond Cytotoxic Payloads for Cancer Therapy. Retrieved July 26, 2020, from McPherson and Hobson. (2020). Pushing the Envelope: The Herald of ADCs Outside of Oncology. Methods Mol Biol., doi: 10.1007/978-1-4939-9929-3-2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Retrieved July 26, 2020, from original title: Deep Inventory: Antibody Conjugate Drug Development Pipeline Explosion, Non-Cancer Indications Will Be the Next "Blue Sea"?