Overview on Current Antibody-drug Conjugate Technology Providers

Posted by Candy Swift on January 3rd, 2019

There are a total of five antibody-drug conjugates that have been approved by the FDA for listing. Among them, Besponsa and Lumoxiti were approved late and there was no actual sales statistics. Mylotarg was approved after delisting without actual market situation in recent years. Therefore,  only Adcetris and Kadcyla can be observed temporarily. Due to the strict limitations of indications and the high cost of treatment, the two drugs grew rapidly in the early stage of the market, and both of them began to slow down in 2015.

The number of ADCs under research projects reported is constantly rising every year, and more than 80 are currently expected to be in the clinical stage. There are many companies that focus on providing ADC technologies services, and they also basically control the technical patents commonly used in this field. For example, Seattle Genetics, ImmunoGen, Immunomedics and Roche's Genentech are early start and leading companies. In recent years, a number of up-and-coming talents have made outstanding contributions to the breakthrough of ADC technology, such as Mersana, ADC Therapeutics.

Seattle Genetics, Inc. was founded in 1998 and is headquartered in Washington, DC, and is the developer of ADCETRIS. The main technology platforms are used for the development of ADCs-related antibodies, ADC linkers and small molecule toxins, as well as antibody structural modifications. Technology has been licensed to companies such as AbbVie, Astellas, Bayer, Celldex, Genentech, GlaxoSmithKline, Pfizer and Progenics, and has been developed in collaboration with companies such as Takeda, Astellas, and Genmab.

Creative Biolabs was established in 2004, of which current research and service capacity covers the entire new drug discovery and development pipeline, ranging from early discovery, pre-clinical evaluations, cGMP manufacturing, to clinical trials. The comprehensive one-stop-shop ADC development services extends from the starting point—antibody identification, to the final destination—creation and evaluation of the ADC, every step of the way.

Immunomedics was founded in Delaware in 1982. Its leading product, Sacituzumab govitecan (IMMU-132), is an antibody drug conjugate of a humanized mAb hRS7 and a topoisomerase inhibitor SN-38 coupled by a covalent bond. hRS7 is a monoclonal antibody against the trophoblast cell surface antigen (TROP-2), expressed on the surface of a large number of human tumor cell surface expression, such as breast cancer. Sacituzumab govitecan has received extensive attention because of its specificity. First of all, its average DAR is as high as 7.6, and in order to improve the water solubility of the ADC and avoid the sinking effect, a 7-polyethylene glycol is introduced between the drug and the antibody. The cleavage moiety is a chemical structure that is said to be unstable to acid; secondly, the activity of the small molecule toxin SN-38 carried by Sacituzumab govitecan is low, altering the usual perception of the cellular activity requirements for antibody conjugate preparation.

Genetic Engineering Technology (Genentech) was first established in 1976 and was acquired by Swiss pharmaceutical giant Roche in 2009 for approximately .8 billion. Genentech's research and development pipelines in the field of biologics range from cancer, Alzheimer's disease, sclerosis, autism, diabetes, kidney disease, asthma, to rheumatism, Crohn's disease and many other fields.

Mersana Therapeutics, Inc. was founded in February 2002 (formerly known as Nanopharma Corp.) and is headquartered in Cambridge, Massachusetts, USA. With Fleximer and Dolaflexin two technology platforms, the first development of polymer linker improved the DAR conjugation. It has established cooperative relationships with heavyweight biopharmaceutical companies such as Merck, Endo, Adimab and Takeda.

Founded in 2011, ADC Therapeutics is based in Lausanne, Switzerland, and uses PBD drug technology. The results of Phase I clinical trials of ADCT-502, an ADC drug that targets HER2, did not show clinical benefit in April 18, and there was a tolerance problem in the dose of the therapeutic effect, and the subsequent clinical trial of ADCT-502 was stopped.

The withdrawal of Mylotarg once hit the market's confidence in ADCs technology, but with the approval of the follow-up products and clinical performance, the attention of ADCs drugs rose again. Advances in technology have led to the expansion of the therapeutic window of ADCs, and the layout of the ADCs' R&D pipelines of major pharmaceutical companies has also been disclosed in recent years. The field has also received high attention from the capital market.