Core B and Core C work synergistically to generate and provide highly drug-like antiviral test articles to be characterized for efficacy in the various AC/DC Projects. Composed in large part by members of the Emory Institute for Drug Development and the Dennis Liotta research group, this entity has collectively identified and developed:
- 2 FDA approved, oral antiviral therapies (Epivir® and Emtriva®)
- 1 FDA authorized, emergency use antiviral for SARS-CoVa infections (molnupiravir)
- 1 Phase 2 antiviral therapy for HBV (EIDD-2173)
- 1 Antiviral (HCV; Enterovirus) therapy (EIDD-2023) ready for IND submission in 2023
Drawing on 200+ years of collective experience in the design and development of drug, Core B provides:
- Design, synthesis and purification of nucleoside and nucleotide analogs and prodrugs.
- Synthesis and purification of nucleotide metabolites (including mono-, di-, and triphosphates) using ion-exchange chromatography to support the evaluation of nucleotide analogs in cell-free polymerase (RdRp) assays and to be used by Core C as bioanalytical standards to support in vitro metabolic studies and in vivo pharmacokinetic and tissue distribution evaluations. Core capabilities and synthetic experience also includes the preparation of 13C-labeled internal standards for bioanalysis.
- Existing, secure compound registry system and data management system, contracted through Dotmatics, inc., capable of tracking compound progression and data acquisition. This system was optimized and validated by regulatory consultants during the successful IND filing of molnupiravir.
- In-house scale-up and process lab and expertise capable of synthesizing kilogram quantities of test article to support advanced Chemistry, Manufacturing and Controls (CMC) and toxicology studies. The kilogram process developed for molnupiravir was transferred to a contracted pilot plant to prepare a 50kg batch of cGMP material with minimal alteration.
- Demonstrated expertise in the iterative synthesis, optimization and advancement of nonnucleoside-based allosteric antivirals arising from high-throughput screens.3-5
- Long-standing collaboration with CMC consultant, Alan Parr, and Emerson Resources, Inc. is in place and will be used to carry out pre-formulation and early CMC activities including polymorph characterization, stability, salt screening and excipient screening.