Scientific Poster: Identification of New Classes of Maytansinoid Payloads for ADCs that Display In Vivo Activity

Introduction

Abzena is the leading Partner Research Organization for ADC research, development, and manufacturing.  With more than XYZ projects with leading pharmaceutical and biotech companies in the ADC field, Abzena has become an extension of its partners’ research teams leading to the successful delivery of the innovative ADCs needed to address unmet medical needs.

In the R&D space, Abzena is the best-equipped CRO to support research efforts in the design, synthesis and evaluation of payloads, linker-payloads, and ADCs.  The close collaboration with our partners, coupled with the skill and ingenuity of our scientists, have resulted in the discovery of novel cytotoxic payloads for all different families including maytansines, auristatins, camptothecins, duocarmycins, pyrrolobenzodiazepines, and others.

The maytansine scaffold has been used to generate ADCs which are at different stages of clinical trials, including an ADC that has been approved by the FDA.  Our talented team of scientists has generated several series of maytansine-based payloads through internal research efforts and in collaboration with numerous partners (Fig 1). Herein, we present the results of a successful collaboration between Abzena and Regeneron Pharmaceuticals.  The main goal of the project was the design and synthesis of novel tubulin inhibitors based on the maytansine core.  These payloads were designed to complement the cell impermeable amino-alkyl maytansinoids that had previously been developed.  The new designs were intended to be capable of cell permeation to increase the so-called “by-stander killer effect”.  Payloads that showed acceptable potency profile were later attached to cleavable linkers and further conjugated to mAbs specific for MUC16 (an ovarian cancer antigen).

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Poster authors include Francisco Velázqueza,*  Thomas Nittolib,*  Frank Delfinob, Marcus Kellyb, Serena Carossoa, Thomas Markotana, Arthur Kunzb, Zhaoyuan Chenb, Shu Maob, Jing Shanb, Elizabeth Navarrob, Feng Zhaob, Sosina Makonnenb, Carlos Hickeyb, Jan Spinka, William Olsonb, Jessica Kirshnerb, Gavin Thurstonb, Nicholas Papadopoulosb.

a- Abzena, 360 George Patterson Boulevard, Bristol PA 19007, USA.  b-Regeneron Pharmaceuticals, Inc.  777 Old Saw Mill River Road,  Tarrytown, NY 10591,  USA