Crestone, Inc. and Praedicare Inc. Announce the Publication of Data on the Novel Antibiotic CRS0540 in the Hollow Fiber System Model of the Orphan Disease Disseminated Listeriosis
Small molecular drugClinical Result
DALLAS, Aug. 15, 2022 /PRNewswire/ -- A potential treatment for listeriosis has been found to be promising in Praedicare's hollow fiber preclinical model of the disease, caused by the bacteria Listeria monocytogenes. Listeriosis has been in the news recently as the bacteria was found in some ice cream and a vegan egg product which were sold to the general public. Listeriosis poses an elevated threat to the susceptible population that is immunocompromised or pregnant.
Crestone, Inc. has been developing a novel inhibitor of bacterial DNA replication, CRS0540, which is active against Listeria monocytogenes and other Gram-positive bacteria, including resistant strains. Praedicare, Inc. has developed a dynamic hollow fiber preclinical model for the disseminated bacteria inside human cells and then tested CRS0540 at concentration versus time profiles expected in patients. Crestone, Inc. and Praedicare Inc. today have announced a publication of the results in a joint publication entitled "Potency of the novel PolC DNA polymerase inhibitor CRS0540 in a disseminated Listeria monocytogenes intracellular hollow-fibre model" in the Journal of Antimicrobial Chemotherapy.
The authors found that CRS0540 demonstrated dose-dependent potency. At sufficient doses, the drug candidate also shut off the bacteria's ability to develop resistance to CRS0540, a major advantage given the current scourge of antimicrobial resistance. One other advantage was that unlike other treatments currently employed for listeriosis, CRS0540 was demonstrated to achieve more than thirty-fold higher concentrations inside infected human cells than outside. Simulations were then used to identify and predict human doses that would be effective in eradicating the disseminated listeria from the infected cells while minimizing antimicrobial resistance. The authors wrote that CRS0540 is one of the first new compounds in development for the treatment of listeriosis in several decades.
"Antibiotics with a novel mode of action and a good safety profile are essential to address the silent pandemic of antimicrobial resistance" said Urs Ochsner, PhD, co-Founder, Vice President of R&D and CEO at Crestone. "CRS0540 dosed orally has already demonstrated efficacy in various animal models of infection caused by drug-resistant staphylococci and streptococci, and now in a hollow fiber model of intracellular Listeria infection."
Tawanda Gumbo, President and CEO of Praedicare Inc. stated that with such impressive efficacy, further studies of CRS0540 were warranted and that "the results also demonstrate that new compounds can be tested rapidly in this preclinical model for sporadic as well as emergent infectious diseases, which can then be immediately translated to clinical scenarios."
This project has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93020C00020.
About CRS0540
CRS0540 is a mechanistically novel oral/IV antibacterial drug candidate that is intended for treatment of infections caused by antibiotic-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), macrolide-resistant Streptococcus pyogenes (Group A strep) and vancomycin-resistant enterococci (VRE), as well as treatment of food-borne illness caused by Listeria monocytogenes. CRS0540 derives from a series of thiadiazole urea compounds that exhibit potent inhibition of PolC, the catalytic subunit of the replicative DNA polymerase in Gram-positive bacteria. As a novel mechanism-of-action agent, CRS0540 has shown activity against all clinically relevant antibiotic-resistant Gram-positive pathogens.
About Crestone, Inc.
Boulder, Colorado-based Crestone, Inc. is a clinical stage biopharmaceutical company focused on inventing and developing novel-mechanism-of-action small molecule drugs for serious bacterial infections. The active pipeline includes antibacterial agents to treat Clostridioides difficile infection (CDI), resistant Gram-positive infections (MRSA, PRSP, and VRE), and chronic infections such as nontuberculous mycobacterial (NTM) disease. For more information please visit: https://www.crestonepharma.com
About Praedicare Inc.
Praedicare Inc. is an end-to-end drug development company, from drug discovery, through preclinical work, to phase IV clinical trials. Praedicare uses preclinical wet lab models mathematically mapped to patients for quantitative prediction of clinical trial outcomes for clinical trial design, significantly reducing clients' risk, time, and costs of developing safe and effective new drugs. For more information please visit: https://praedicareinc.com/
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