Curza Inc

A New Class of Broad-spectrum Antibacterial Agents to Treat Multi-drug Resistant Pathogens - Project Summary Curza Is Developing the CZ-02 Platform of Broad-spectrum Antibiotics as a New Class Focusing on Multidrug- Resistant (MDR) Gram-negative Pathogens That Will Also Be Efficacious Against Gram-positive Bacteria. CZ-02 Antibacterials Bind to a Unique Site on the Bacterial Ribosome That Is Not Targeted by Antibiotics Available Clinically Which Is Expected to Limit Cross-resistance to Other Antibiotics. the Initiation and Subsequent Development of the CZ-02 Program Represents a Strong Example for Revisiting the Use of Natural Products in Drug Discovery Which Has Fallen Out of Favor in Pharma. CZ-02S Were Inspired by the Natural Product Amicetin Which Selectively Inhibits Bacterial Protein Synthesis But Suffers From Limited Antibacterial Activity and Poor Drug-like Properties. Careful Engineering of the Natural Product Has Produced CZ-02S With Exquisite Selectivity for Bacterial Protein Synthesis, Potent Antibacterial Activity and Excellent Drug-like Properties That Have Demonstrated Efficacy Against MDR Pathogens in Multiple Animal Models of Infection While Sparing Mammalian Cells From Cytotoxicity. the Goal of This Direct-to-phase Ii Project Is to Develop a New Antibacterial Drug Candidate That Covers Gram- Negative Pathogens Found Among Enterobacterales and the Non-fermenters Acinetobacter Baumanni and Pseudomonas Aeruginosa as Well as Gram-positive Pathogens. the Initial Clinical Indication Will Be for Treating Urinary Tract Infections (utis), With Other Indications to Follow (e.g. Complicated Intra-abdominal Infections, Pneumonia, Bacteremia). at the Conclusion of This Phase Ii Sbir Will Be a Pre-clinical Development Candidate That Is Potent With Broad Spectrum Activity That Will Be Ready for Chemistry, Manufacturing and Controls (CMC) and Toxicology/safety Pharmacology Under Good Laboratory Practices (GLP). Advancement of This Antibacterial Lead Series Will Be Accomplished by the Following Aims. Aim 1 Will Expand the Spectrum of Activity for Advanced Leads That Have Shown Efficacy in Uti Animal Models With MDR Gram-negative Pathogens. Curza’s Proprietary Model for Producing Potent and Selective Inhibitors of Bacterial P-site Protein Synthesis, in Combination With a Battery of Biological/biochemical Activity Assays (biochemical, Microbiological, in Vitro Adme-tox), Will Be Used for Chemistry Efforts to Ensure Compounds Retain Activity While Expanding the Spectrum of Addressable Pathogens to Include a. Baumannii and P. Aeruginosa. Aim 2 Will Define Pharmacokinetics (PK) While Identifying the Maximum Tolerated Dose and Confirming Efficacy by Testing in Thigh Infection Models to Select CZ-02S for Evaluation in Uti Models. a Lead and Backup Drug Candidate Will Be Selected in Aim 3 by Evaluation in Uti Models of Antibiotic-resistant Bacteria Followed by Non-glp Toxicology in Rats to Nominate a Lead and Backup. Aim 4 Will Scale-up Production (non-glp) to Support in Vivo Studies While Aim 5 Will Establish the Optimal Dosing Strategy From Pk/pharmacodynamic (PD) Studies.