Earlier this year, a record number of 2,300 delegates attended the 13th edition of the “PEGS: The Essential Protein Engineering Summit,” held May 1 – 5, 2017 at the Seaport World Trade Center in Boston’s vibrant Seaport District. Among the many presentations focusing on innovating next generation ADCs by improving target selection, finding new cytotoxic drugs as payloads, engineering antibodies or discovering alternative effector moieties to increase half-lives and improve target specificity, optimizing linker-payload chemistry to produce stable and homogeneous ADCs, and overcoming the challenges of multi-drug resistance, Morphotek’s Principal Scientist Jared Spidel, Ph.D., presented the latest data about the company’s REsidue-SPEcific Conjugation Technology (RESPECT™).
RESPECT™ is a site-specific conjugation technology that targets select amino acid residues as a way of producing investigational homogeneous Antibody-drug Conjugates or ADCs with defined drug-to-antibody ratios.
The REsidue-SPEcific Conjugation Technology cysteine-specific conjugation method exploits a unique intrachain disulfide bond in the light chain of rabbit antibodies between cysteine residues at 80 and 171 of the variable and constant domains. Morphotek humanization strategy allows retention of the C80 with a free thiol group that is amenable for residue-specific conjugation. The company’s C-terminal lysine-specific linkage method employs the transglutaminase enzyme catalyzing formation of an isopeptide bond between the IgG C-terminal K447 and a variety of glutamine-based payloads. ADCs prepared using our RESPECT technology produced uniform drug-to-antibody ratios and were shown to be highly potent and specific in vitro and in vivo.
As such, the platform allows for site-specific conjugation of a single cytotoxic payload or two payloads with different mechanisms of action. Site-specific conjugation has shown to eliminate heterogeneity, improve conjugate stability, and increase the therapeutic window.
Morphotek’s RESPECT platform also employs a proprietary high-throughput screening system that can simultaneously evaluate hundreds of different ADC products consisting of variable antibody candidates linked to cytotoxic payloads to identify those optimal for client-desired biophysical properties, target-specific binding and therapeutic efficacy. As part of it’s ADC services, Morphotek, a subsidiary of Eisai, offers a proprietary payload, which incorporates eribulin modified with a chemical linker, as an option to develop investigational ADCs for companies interested in developing next-generation formats for their own antibodies.
“We were pleased to have this opportunity to present our proprietary RESPECT platform at the PEGS Summit,” noted Nicholas C. Nicolaides, Ph.D., the current President and CEO and a co-founder of Morphotek.
“[We’ve] highlighted the unique advantages that this platform offers to those interested in developing next-generation ADC-type products,” Nicolaides added.
Morphotek’s end-to-end ADC Services business was launched in early April 2017. The service allows for multiple entry points for clients, starting from development of a site-specific bioconjugate-ready monoclonal antibody and ADC to in vivo safety and efficacy validation. Additional options include manufacture of GMP clinical trial material, GLP toxicology studies and/or development of IHC companion diagnostics for patient screening.
Commenting on the launch of the company’s ADC Service, Nicolaides said: “Decades of expertise in antibody engineering and clinical development of biologics-based therapies, along with preclinical studies showing the potential of our new ADC formats, has enabled us to align these assets into a client-focused ADC business offering end-to-end services [and we] believe [that] this new service provides an opportunity to build a win-win strategy by increasing internal value through leveraging our proprietary platforms and development know-how, and customer value by developing ADCs to their strategic targets.”