The Clinical Landscape of Antibody-drug Conjugates

Emerging formats for next-generation antibody drug conjugates

“…Can a high dose of a smaller ADC provide a short, sharp 'hit' to penetrate deeply and irreversibly damage the tumour followed by a quick exit to spare the side effects and will this give a wider TI compared to a longer acting, prolonged exposure from a larger format? It is possible that some solid tumours will benefit from the former, particularly if the correct target is addressed, but as only onethird of ADC clinical trials are for solid tumours, this data will be slow to come [3]. The pharmacokinetics of ADCs may eventually have to be tailored on a case-by-case basis to maximise the TI.…”

“…The idea of delivering a small molecule cytotoxic drug (payload) to a tumour cell using MAbs is almost as old as the idea of using MAbs as targeted therapeutics, but research approaches and technologies have re-invented themselves many times after repeated setbacks. At last, with two recently approved ADC drugs and a clinical development pipeline estimated at around 47 unique products in 228 clinical trials [3,4], the technology has firmly established itself in the biopharmaceutical arsenal driving R&D expansion, investment and technical approaches that would not have been feasible 10 or even 5 years ago.…”

Antibody-drug conjugates: Intellectual property considerations

“…Interestingly, of 47 ADC candidates in clinical studies as of 2014, 14 16 candidates use maytansinoids, while 22 candidates use auristatins. In most cases, a license, or a purchase of the respective toxin, from ImmunoGen, or Seattle Genetics, respectively, would be necessary, because these 2 companies are the major IP holders regarding these toxins, or toxin-linker combinations (see Table 7).…”

“…Other classes are in clinical or preclinical trials, 20 including pyrrolobenzodiazepines and other benzodiazepine derivatives, duocarmycins, tubulysins, a-amanitin or bouganin protein toxin (see Table 7). …”

“…More than 40 other ADCs are in clinical studies today. 2 ADCs combine an antibody, a linker and a toxin (often called "payload" or, more martial, "warhead"), and, for that reason, they are technically demanding to develop and pose challenges in manufacturing. 3 They can also raise regulatory issues.…”