First-in-Class S. aureus α-Hemolysin Inhibitors for Lung and Skin Infections

Reference Number TO 02-00373

Keywords

Virulence factor, MRSA, HAP, VAP, α-hemolysin, small molecule, inhibitor, pathoblocker

Invention Novelty

First-in-class inhibitors of virulence factor α-hemolysin for the prophylaxis and treatment of lung (HAP/VAP) and skin infections (atopic dermatitis) caused by Staphylococcus aureus.

Value Proposition

Main target: α-hemolysin (Hla) is the dominant S. aureus virulence factor and a clinically validated target
Biomarker development: a biomarker is being developed to better stratify VAP/HAP patients to trial size
Target engagement: Hla inhibitor prevents cytotoxicity in human epithelial cells, as well as NK cells, restores endothelial cells integrity and adherent junctions in primary cultures, and prevents the formation of conduction channels (pore formation)
Funding: Successful CARB-X, INCATE, and other institutional funding applications
Highlighting the potential to meet an unmet medical need in Staphylococcus-associated lung and skin infection management.

Survival in a mouse model of S.aureus infection (Shekhar et. al., 2025).

Technology Description

In vitro activity: EC50 = 5-50 nM with negligible cytotoxicity
Binding activity: ligand pocket identified via NMR
In vivo activity: Reduction of bacterial lungburden (~3 log units) and plasma IL-6 vs vehicle
In vivo PoC: Pre-emptive and/or adjunctive treatment with linezolid shows complete recovery of mice with high disease scores

Commercial Opportunity

The technology is available for co-development and in-licensing partnerships.

Development Status

Initiating regulatory preclinical development in VAP and colonized skin lesions in atopic dermatitis.

Patent Situation

Patent family based on WO2023/280970, with subsequent WO2024/133220 as a follow-up application. Applications in the EU, US, CA, JP, and AU are pending.