An important difference between Besponsa and Lumoxiti is the cytotoxic payload each carries – respectively calicheamicin, the same as that used in Pfizer’s Mylotarg, and Pseudomonas exotoxin A. And both drugs’ labels carry boxed warnings, respectively for liver damage and capillary leak syndrome, the toxicity that briefly derailed Stemline’s anti-CD123 conjugate SL-401. The next anti-CD22 asset to test the regulators could be Immunomedics’ epratuzumab, though as this is a standard . Antibody-drug conjugates (ADCs) represent one of the most promising and exciting areas of anticancer drug discovery. Five ADCs are now approved in the US and EU [i.e., ado-trastuzumab emtansine (Kadcyla (TM)), brentuximab vedotin (Adcetris (TM)), inotuzumab ozogamicin (Besponsa (TM)), gemtuzumab ozogamicin (Mylotarg (TM)) and moxetumomab . The technology is based on the concept of delivering a cytotoxic payload selectively to cancer cells by attaching it to an antibody targeted to antigens on the cell surfaces. This approach has several advantages including the ability to select patients as likely responders based on the presence of antigen on the surface of their cancer cells and a wider therapeutic index, given that ADC . While the needed monoclonal antibody falls in the domains of biology and biochemistry, the potent payload and the linker belong to the realm of chemistry. Naturally occurring molecules and their derivatives endowed with high cytotoxic properties have proven to be useful payloads for the first approved ADCs (i.e., Mylotarg, Adcetris, Kadcyla, and Besponsa). The latest approaches and intensifying activities in this new paradigm of cancer therapy demands a variety of payloads with different . Currently, there are four antibody-drug conjugates (ADCs) approved by US FDA: Mylotarg (2000, withdrawn in 2010), Adcetris (2011), Kadcyla (2013) and Besponsa (2017), while the second one Adcetris (the generic name is Brentuximab vedotin) is an auristatin-based ADCs. Adcetrisis formulated by the conjugation of brentuximab, an anti-CD30 (also known TNFRSF8) monoclonal antibody with payload . Notably, Besponsa’s cytotoxic payload ozogamicin is the same as that used in the company’s Mylotarg. This was pulled in 2010 after 10 years on the market owing to concerns about toxicity and lack of benefit in acute myeloid leukaemia, but recently earned a positive adcom vote that could see its US re-approval by September..