Best-In-Class P. aeruginosa LasB virulence factor Inhibitors

Reference Number TO 02-00378

Keywords

Elastase, LasB, virulence inhibitor, pathoblocker, lung infections

Invention Novelty

Best-in-class inhibitors targeting the extracellular zinc metalloprotease LasB, demonstrating exceptional activity and safety profiles, to different Pseudomonas infections.

Value Proposition

Main target: LasB contributes to tissue damage and suppresses the immune system during infection
Adjunctive therapy candidate: Combining LasB inhibition with levofloxacin or meropenem significantly reduces bacterial burden without interfering with the antibiotic mechanism
Excellent safety profile: No cyto- or genotoxicity, no off-targets, nor activity towards the most relevant human metalloproteases and further 87 possible human off-targets
These features highlight the potential to meet an unmet medical need in Pseudomonas infection management.

Antibiotic efficacy in models of P. aeruginosa infection with two different delivery methods (Konstantinovic et. al., 2023).

Technology Description

In vitro activity: Low to sub-nM IC50 values
In vitro and in vivo ADME/T: Good solubility, excellent plasma- and metabolic stability, and good tolerability
In vivo target engagement: Reduction of cfu/g of tissue, circulating LasB, and clinical scores in two infection models. Prolonged survival of mice under adjunctive therapy
Anti-keratitis effect: Synergistic and significant effect when given in combination with meropenem (0.5 mg/ml)

Commercial Opportunity

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

Development Status

Proof-of-concept in Pseudomonas lung infections, as well as Pseudomonas keratitis mouse models.

Patent Situation

Two international PCT applications have been filed (WO2022043322A1 and WO2023166039). National phases were initiated in 2023 in EP, US, CN, JP, AU, IL, and CA. Another European-priority application was filed in May 2024 (EP24 178 040.2).