Recipient organisationThe Wistar InstituteSource-published name: Wistar Institute
Funding£1.9M
PeriodNov 2014 — Mar 2019
In plain English
AI plain-English summary
A single viral protein, EBNA1, keeps the Epstein-Barr virus alive inside infected cells, and this project aims to develop a drug that blocks it. Epstein-Barr virus infects most people and stays dormant for life, but in some cases it drives cancers such as nasopharyngeal carcinoma, Burkitt’s lymphoma, and gastric cancer, as well as autoimmune conditions like multiple sclerosis. Current treatments target the cancers themselves, not the underlying viral infection. EBNA1 is essential for the virus to persist and for tumour cells to keep dividing, making it a validated but untapped drug target. If successful, this project will produce a clinical candidate ready for first-in-human trials. The researchers plan to optimise existing lead compounds for better stability and exposure in the body, then run the full suite of safety and toxicology studies required for an Investigational New Drug application. A Phase 1 trial would test whether blocking EBNA1 can safely disrupt latent infection. That could eventually lead to a treatment that targets the root cause of several EBV-driven diseases, rather than managing their symptoms.
View original technical description
The primary objective of the proposal is to develop a safe and efficacious clinical candidate to treat oncogenic Epstein-Barr Virus (EBV) and associated disease. Infection of EBV is etiologically linked to several malignancies, including nasopharyngeal carcinoma, Burkitt's lymphoma, gastric carcinoma and lymphoproliferative disease of the immunosuppresed. EBV latent infection may also contribute to auto-immune disease, including multiple sclerosis. Maintenance of latent EBV depends on the continuous expression of one viral protein, EBNA1. EBNA1 is essential for tumor cell proliferation in EBV-associated malignancies and is a validated target for inhibition of EBV-dependent B-cell transformation and lymphomagenesis. In this advanced stage application, we propose three milestones: (M1) We will identify a clinical candidate by optimizing our advanced leads to maximize in vivo exposure, increase metabolic stability and decrease plasma protein binding. (M2) We will perform the necessary studies to support an IND application including formulation studies, GMP batch production, analytical methods development and GLP toxicology in 2 species. We will perform safety pharmacology studies including cardiovascular and respiratory safety studies and GLP genotoxicity studies. (M3) Using the information from the preclinical studies, we will plan and coordinate activities to begin clinical trial studies. We will identify a clinical trial sponsor, develop the protocols and set enrollment targets. We will also write and file an IND application to bring one pre-clinical candidate into Phase 1 first-in-human clinical trials.
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