Delving into the Latest Updates on Eldec Pharmaceuticals, Inc. with Synapse

Overview

Basic Info

Introduction

Established by the entrepreneurial efforts of Drs. Saira Ahmad, Flori Sassano, and Robert Tarran, Eldec Pharmaceuticals Inc. emerged from UNC-CH in 2017. Research from Dr. Tarran's lab, focusing on SPLUNC1's impact on chronic lung inflammation, was pivotal in the company's inception. Dr. Tarran identified a key C-terminal SPLUNC1 sequence that regulates the Orai1 Ca2+ channel in immune cells, laying the foundation for Eldec's primary drug development initiative.

Tags

Respiratory Diseases

Infectious Diseases

Small molecule drug

Disease domain score

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Technology Platform

Most used technologies in drug development

Targets

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Disease Domain	Count

Infectious Diseases	1

Top 5 Drug Type	Count

Small molecule drug	1

Top 5 Target	Count

BPIFA1 x ORAI1	1

Author: Krajewski, Krzysztof ; Voeller, Alexis ; Goriounova, Alexandra S. ; Abdelwahab, Sabri H. ; Thickett, David R. ; Iskarpatyoti, Jason A. ; Moran, Timothy P. ; Rai, Mani ; Wrennall, Joe A. ; Mahida, Rahul Y. ; Sassano, M. Flori ; Ignar, Diane M. ; Ahmad, Saira ; Tilley, Stephen L. ; Sekhri, Malika ; Ghosh, Arunava ; Greenbaum, Alon ; Tarran, Robert

Rationale: Acute respiratory distress syndrome (ARDS) has an unacceptably high mortality rate (35%) and is without effective therapy. Orai1 is a Ca²⁺ channel involved in store-operated Ca²⁺ entry (SOCE), a process that exquisitely regulates inflammation. Orai1 is considered a druggable target, but no Orai1-specific inhibitors exist to date. Objectives: To evaluate whether ELD607, a first-in-class Orai1 antagonist, can treat ARDS caused by bacterial pneumonia in preclinical models. Methods: ELD607 pharmacology was evaluated in HEK293T cells and freshly isolated immune cells from patients with ARDS. A murine acute lung injury model caused by bacterial pneumonia was then used: mice were infected with Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant S. aureus, or multidrug-resistant P. aeruginosa and then treated with ELD607 intranasally. Measurements and Main Results: ELD607 specifically inhibited SOCE in HEK293T cells with a half-maximal inhibitory concentration of 9 nM. ELD607 was stable in ARDS airway secretions and inhibited SOCE in ARDS immune cells. In vivo, inhaled ELD607 significantly reduced neutrophilia and improved survival. Surprisingly, Orai1 inhibition by ELD607 caused a significant reduction in lung bacteria, including methicillin-resistant S. aureus. ELD607 worked as an immunomodulator that reduced cytokine levels, reduced neutrophilia, and promoted macrophage-mediated resolution of inflammation and clearance of bacteria. Indeed, when alveolar macrophages were depleted with inhaled clodronate, ELD607 was no longer able to resolve inflammation or clear bacteria. Conclusions: These data indicate that specific Orai1 inhibition by ELD607 may be a novel approach to reduce multiorgan inflammation and treat antibiotic-resistant bacteria.

100 Deals associated with Eldec Pharmaceuticals, Inc.

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100 Translational Medicine associated with Eldec Pharmaceuticals, Inc.

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Pipeline

Pipeline Snapshot as of 26 Dec 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

1

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