Author: Zambriski, Jennifer A. ; Xiao, Linda ; Watson, Lucy C ; Manjunatha, Ujjini H ; Diagana, Thierry T. ; Gable, Jonathan E. ; Sarko, Christopher ; Young, Joseph M ; Chen, Ying-Bo ; Lu, Peichao ; Osborne, Colin S ; Gable, Jonathan E ; Aziz, Natasha ; Manjunatha, Ujjini H. ; Lakshminarayana, Suresh B ; Turner, Michael ; Luu, Catherine ; Zambriski, Jennifer A ; Patra, Debjani ; Galarneau, Jean-Rene ; Jumani, Rajiv S. ; Darrell, Kristen H. ; Watson, Lucy C. ; Mamo, Mulugeta ; Lakshman, Jay ; Cantwell, John ; Carney, Shannon K ; Chao, Alexander T ; Shaul, Jacob ; Young, Joseph M. ; Jumani, Rajiv S ; Osborne, Colin S. ; Chao, Alexander T. ; Lakshminarayana, Suresh B. ; Diagana, Thierry T ; Chan, Katherine ; Cuellar, Carlos ; Hanna, Imad ; Darrell, Kristen H ; Kulkarni, Upendra ; Knapp, Mark ; Carney, Shannon K.

Diarrhoeal disease caused by Cryptosporidium is a major cause of morbidity and mortality in young and malnourished children from low- and middle-income countries, with no vaccine or effective treatment. Here we describe the discovery of EDI048, a Cryptosporidium PI(4)K inhibitor, designed to be active at the infection site in the gastrointestinal tract and undergo rapid metabolism in the liver. By using mutational analysis and crystal structure, we show that EDI048 binds to highly conserved amino acid residues in the ATP-binding site. EDI048 is orally efficacious in an immunocompromised mouse model despite negligible circulating concentrations, thus demonstrating that gastrointestinal exposure is necessary and sufficient for efficacy. In neonatal calves, a clinical model of cryptosporidiosis, EDI048 treatment resulted in rapid resolution of diarrhoea and significant reduction in faecal oocyst shedding. Safety and pharmacological studies demonstrated predictable metabolism and low systemic exposure of EDI048, providing a substantial safety margin required for a paediatric indication. EDI048 is a promising clinical candidate for the treatment of life-threatening paediatric cryptosporidiosis.

100 Deals associated with EDI-048

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Cryptosporidiosis	Phase 1	GB	Novartis AG	29 Apr 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

EDI-048

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation