Targeted protein degradation (TPD) has emerged as novel technology in drug development. This approach offers the potential to tackle disease-causing proteins that historically were very challenging to target with conventional small molecule therapeutics.[1]

In the 20 years since the first concepts of a targeted protein degradation were reported, TPD has moved from academic research to industry development, with numerous companies involved in preclinical and early clinical development. With the clinical proof-of-concept for targeted protein degradation molecules against estrogen receptors (ER) and the androgen receptors (AR), well-established targets anti-cancer drug development, the field op TPD research, designed to tackle ‘undruggable’ targets and other classes of difficult protein targets.[1]

A comprehensive toolkit
In the development of novel development tools Catalent has recently launched ProteoSuiteSM Oral suite, a comprehensive toolkit that offers the rational selection and  developability assessment specific to protein degrader candidates and their advancement into clinical trials.  The toolkit is especially designed to helps identify orally bioavailable drug candidates and leverages an array of specialized capabilities to select the right drug formulation to efficiently get to the clinic. [2]

These emerging therapeutic modalities are typically highly potent and present novel oral bioavailability challenges to formulators.

Catalent’s new ProteoSuite Oral platform leverages the company’s 90-year track record of advancing complex molecules for oral drug development, including experience with multiple protein degrader programs, together with the development of custom TPD-specific assays and physiologically based pharmacokinetic (PBPK) and developability models.

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Drug developers using the service benefit from the identification of those orally developable drug candidates with the greatest chance of success, and, in addition, a development path to the clinic with consideration of the necessary advanced formulation technologies such as lipid-based delivery and amorphous solid dispersions, as well as manufacturing, specialty handling, and integrated clinical supply capabilities to accommodate these highly potent molecules.

Significant promise
Targeted protein degraders show significant promise in therapeutic areas such as oncology and beyond, but because of their complex structures, and physico-chemical properties, achieving satisfactory oral exposure can be challenging. They also present additional formulation and handling challenges.

Julien Meissonnier is Vice President and Chief Scientific Officer at Catalent. Meissonnier is part of the company’s’ executive leadership team heading up the company’s scientific community and customer advisory partnerships and helping to improve formulation and adoption of new drug delivery technologies.

“Targeted protein degraders have the potential to revolutionize new small molecule therapies, but if they are to be successful oral treatments, they require a rational approach to development and a comprehensive toolkit of proven technologies to address their ‘not so small’ characteristics and potency,” explained Julien Meissonnier, Catalent’s Vice President and Chief Scientific Officer.

“This new service provides customers with a logical and comprehensive development path, access to Catalent’s multi-center manufacturing capabilities designed to handle highly potent compounds, and its experience in scaling up and advancing successful products to market.”

Early phase development
Catalent’s network of early phase development sites includes facilities in St. Petersburg, Florida, San Diego, and Somerset, New Jersey, in the U.S., as well as Nottingham, U.K., and Beinheim, France. Development of targeted protein degraders at these sites will be supported by analytical, scale up and commercial sites with specific capabilities in handling potent drug products in Greenville, North Carolina, Kansas City, Missouri, Winchester, Kentucky, St. Petersburg, Beinheim, and Schorndorf and Eberbach in Germany.

Reference
[1] Zhong Y, Chi F, Wu H, Liu Y, Xie Z, Huang W, Shi W, Qian H. Emerging targeted protein degradation tools for innovative drug discovery: From classical PROTACs to the novel and beyond. Eur J Med Chem. 2022 Mar 5;231:114142. doi: 10.1016/j.ejmech.2022.114142. Epub 2022 Jan 20. PMID: 35092900.
[2] Introducing ProteoSuite℠ Oral: A Comprehensive Oral Developability Assessment and Drug Delivery Solution for Targeted Protein Degraders. Catalent. Online. Last accesses on March 29, 2023

Featured image: Catalent Exhibition Booth/CPhI 2016 Photo courtesy: © 2016 – 2023. Sunvalley Communication/Evan Wendt. Used with permission.

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