A library of well-characterized, first- and second-generation low-toxicity ADC surrogates available at multi-gram scales will provide manufacturers, vendors and academics with access to materials for ADC process, formulation and analytical research and development efforts as well as for the training of personnel in the safe handling of ADCs without the severe exposure risk and containment burden. For manufacturers, this will permit faster process development and validation in less expensive development suites, outsourcing of process development efforts, greater experimentation and optimization, performance comparisons/validation among global manufacturing sites and/or CROs/CMOs and development of process and analytical performance standards for ADC regulatory filings.
A significant amount of preliminary work was completed in PC2.2-109, where two linker-fluorheads conjugates (LFCs) were successfully
synthesized and showed good agreement with the physical properties of their linker-drug counterparts. In the process of completing these tasks, we were able to assess supply chain issues, identify hazardous materials, evaluate costs to manufacture sADCs. The assays we propose to use here are taken directly from the literature. (Liu et al. 1996; Xu et al. 2011; Valliere-Douglass et al. 2012; Wagh et al. 2018; Procopio-Melino
et al. 2022) Additionally, there are literature reports of other non-toxic sADCs, including one using he NISTmAb as a substrate for linkers and surrogate payloads. (Agnew et al. 2021) This published report, along with our Final Report for PC 2.2-109, provides independent verification
of the sADC synthetic approach.
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Rensselaer Polytechnic Institute
Carnegie Mellon University
MilliporeSigma/EMD Serono
Pfizer, Inc.
