Sir Charles Tupper Medical Building, Dalhousie University Suite 1A-1; 5850 College Street Halifax, Nova Scotia B3H 4H7
Krembil Discovery Tower, 60 Leonard Ave 4KD473, Toronto, Ontario M5T 0S8
Our Discovery highlights DeNovaMed’s unique approach in targeting ACP synthase to disrupt lipid metabolism in bacteria. This approach is pivotal in the development of novel antibiotics to combat both Gram-positive and Gram-negative bacteria, addressing the critical issue of antibiotic resistance.
This is a lead compound identified as a first-in-class antibiotic from a de novo design campaign of over 750 new chemical entities. DNM0547 demonstrates high skin permeability, which provides high potential for topical treatment in Stage 1 and 2 Diabetic Foot Ulcers (DFUs). A mixture of DNM0547 and colistin is being studied for more advanced DFUs. DNM0547 has shown successful outcomes in several preclinical tests, including against many major multidrug-resistant bacteria. DNM0547 also finds potential use in the treatment of other conditions such as MRSA infections, cellulitis, drug resistant bacterial, ischemic limb and peripheral arterial infections.
DNM0547 works as follows:
Targeting ACP Synthase: DNM0547 works by targeting ACP synthase, a bacterial protein essential for life and not a target of current antibiotics. This unique mode of action disrupts a crucial process in bacterial lipid metabolism.
Computer-Aided Drug Design: The compound was developed through computer-aided drug design, which involved synthesizing and testing 750+ compounds to identify those with the most effective properties.
Selection for Topical Delivery: Out of the synthesized compounds, 80 showed activity against a broad spectrum of Gram-positive bacteria found in Diabetic Foot Ulcers (DFUs), leading to the selection of DNM0547 due to its unique properties, including high skin permeability and effectiveness for topical treatment of early-stage DFUs
Therapeutic Areas: Diabetic Foot Ulcers, Cellulitis, Skin Infections, Peripheral Arterial Disease Infections, Ischemic Limb Infections.
DNM0904 is a novel antibiotic developed by DeNovaMed effective against Gram-positive bacteria (such as MRSA) and Gram-negative bacteria in conjunction with colistin. It has shown to perform exceptionally well versus multi-drug and colistin resistant strains. In tests, we determined the Minimum Inhibitory Concentration (MIC) of DNM 0904 against various Gram-positive strains and DNM0904/colistin for battling E. coli, K. pneumoniae, and A. baumannii. The MIC results were 0.01 – 0.03 in all cases, indicating highly effective performance.
Our ultimate goal is to leverage the strength of stand alone DNM0904 and in combination with colistin to combat rising bacterial resistance and provide relief in terms of global economic loss and prevent potential setbacks in public health and industries. DNM0904 has been optimized for application in complex cases where other existing antibiotics are ineffective, bolstering our medical arsenal’s strength and responsiveness in future health-related crises.
DNM0904 works as follows:
Targets ACP Synthase, a new target for antibiotics, where the mechanism is to disrupt a crucial process in bacterial lipid metabolism.
Computer-Aided Drug Design: Over 750 compounds were synthesized and tested to arrive at those with the most effective properties.
Synergy with Colistin: DNM0904 demonstrates synergistic effects when used with colistin against multi-drug-resistant (MDR) Gram-negative bacteria. This synergy could enable the use of lower, non-toxic doses of colistin while maintaining treatment efficacy, especially important given the nephrotoxic nature of colistin
Therapeutic Areas: Gram-positive and Gram-negative systemic infections (multi-drug-resistant), Leprosy and Anthrax (bioterrorism applications).
Broad-Spectrum Effectiveness: DNM0904 is effective against a wide range of pathogens, including Gram-positive and a variety of Gram-negative bacteria.
Standalone Activity against Anthrax: Exhibits strong standalone antibiotic activity against various strains of B. anthracis, making it a potential key player in biodefense strategies.
Synergy with Colistin: Shows synergistic effects with colistin (polymyxin) against multi-drug-resistant (MDR) Gram-negative bacteria. This synergy could allow for lower, less toxic doses of colistin while maintaining treatment efficacy.
Efficiency Against Colistin-Resistant Strains: Demonstrates effectiveness even on colistin-resistant strains, indicating a potential for overcoming some existing antibiotic resistance hurdles.
Lead Optimization and Patent Protection: As of now, DNM0904 is at the lead optimization stage in animal models of infection, with provisional patents filed, ensuring intellectual property protection and paving the way for further development and commercialization