Since the approval of the first antibody-drug conjugate or ADC, now more than 15 years ago, scientists and researchers have sent more than 50 ADCs to be clinically evaluated in ongoing clinical research programs. While some of the trial results have indeed been impressive, some of the results have been mixed. At a time when some may worry about a high rate of attrition, researchers have correctly pointed out that a high rate of attrition in phase I and II means that only the best trial drugs advance to phase III trials and beyond.
In reviewing the cause of failure of antibody-drug conjugates in clinical trials, researchers are looking at a great number of reasons, including the possibility of linker instability as one possible aspect causing systemic toxicity. But they are also asking if failure may be caused by safety concerns with maximum tolerable dose and low therapeutic index. Why does preclinical data not translate to clinical efficacy in human? Are these problems caused by an insufficient understanding of antibody-drug conjugate metabolism in vivo?
This year, from February 8 – 10, 2016, Hanson Wade’s World ADC Summit will be in Berlin, Germany, where leading Experts and Key Opinion Leaders from academia and companies, including Seattle Genetics, Genentech/Roche, Pfizer, MedImmune, Immunomedics and others, will present new antibody-drug conjugates research, insights and updates. During this meeting, researchers and scientists are expected to share their latest understanding and, above all, lessons learned from preclinical and clinical studies to see how this may help in the development of the next-generation antibody-drug conjugates, and move the industry forward in the right direction.
From discovery to clinic
Over a 3 day period and with more than 60 sessions the World ADC Summit is expected to cover every aspect of antibody-drug conjugate development from discovery, preclinical, clinical and market development. Furthermore, the latest advancements making the development of the next generation therapeutically successful antibody-drug conjugates will be presented.
The meeting is expected to cover how Seattle Genetics is developing high-DAR ADCs with superior in vivo performance using innovative linker designs. Other sessions will discuss how to enhance chances of successful regulatory approval by hearing views from the U.S. Food and Drug Administration (FDA), how to effectively scale up from clinical to commercial manufacturing and how to create and maintain a robust antibody-drug conjugate manufacturing CMO network.
During the meeting, researchers are also expected to discuss the successful develop of payloads with different mechanisms of action and specific lesson learned from the synthesis and development of novel pyrrolobenzodiazepine (PBD) dimers as potent anticancer agents with a broad spectrum anti-tumour activity in vivo.
Other topics to be discussed include how to overcome serum stability issues associated with thiol linked antibody drug conjugates using N-alkyl maleimides from MedImmune, how to identify novel antibody-drug conjugate targets which have improved internalisation at a higher frequency based on insight from Genmab, improving understanding of IgG limitations and discover validated alternative antibody formats with Roche.
The attendees can also expect to hear from experts from Pierre-Fabre discussing how to improve pharmacokinetic understanding using cutting edge analytical and bioanalytical characterisation approaches, listen to researchers from Bayer talking about maximizing the antibody-drug conjugate drug therapeutic window by learning how to effectively manage off-target toxicities and, finally, get a better understanding of the latest clinical outcomes by reviewing results for Immunomedics‘ clinical phase II trial with IMMU-132 in patients treated for solid cancers who have had multiple prior therapies.