Melinta Therapeutics’ delafloxacin shows potent and rapid antimicrobial activity against Neisseria gonorrhoeae

NEW HAVEN, Conn.—Melinta Therapeutics today announced results from in-vitro studies that highlight the potential of delafloxacin, an investigational fluoroquinolone, to target Neisseria gonorrhoeae, the causative organism of gonorrhea. N. gonorrhoeae has developed resistance to all classes of antimicrobials previously recommended for treatment of the disease, leaving only one cephalosporin, ceftriaxone, as a recommended first-line treatment. The studies highlighted below demonstrate delafloxacin's rapid and potent in-vitro activity against N. gonorrhoeae, including isolates resistant to other fluoroquinolones, the company noted in a statement.

"Delafloxacin is the most active fluoroquinolone we've tested across bacterial species, including N. gonorrhoeae. As a whole, these studies highlight delafloxacin's robust in-vitro activity against even highly resistant N. gonorrhoeae strains. Importantly, this activity has been shown to be rapid and not thwarted by common resistance mechanisms," noted Dr. Erin Duffy, Melinta's chief scientific officer. "Delafloxacin is currently in Phase 3 to assess its potential to treat uncomplicated gonorrhea. The results of these in-vitro studies provide strong support for its clinical potential.

In a pair of studies with external collaborators at the University of Washington and the University of Alabama at Birmingham, Melinta scientists tested the robustness of delafloxacin against ciprofloxacin-resistant clinical isolates of N. gonorrhoeae. Delafloxacin demonstrated activity against all 50 of the ciprofloxacin-resistant isolates tested at the University of Washington, showing minimum inhibitory concentrations (MICs) between 0.004 and 0.125 µg/mL. Against the 100 isolates tested at the University of Alabama at Birmingham, the MIC range for delafloxacin was 0.016-0.0625 µg/mL, while the MIC range for ciprofloxacin was 0.06-16 µg/mL.

In a separate in-vitro study, delafloxacin was shown to be more rapidly bactericidal against both ciprofloxacin-susceptible and -resistant N. gonorrhoeae strains than was ceftriaxone. In this study, against three susceptible strains of N. gonorrhoeae, delafloxacin was bactericidal at two-to-four hours compared to six-to-eight hours for ceftriaxone. Importantly, delafloxacin showed rapid bactericidal activity at six hours against a resistant strain, against which ceftriaxone had no effect.

Finally, in collaboration with researchers at Emory University and the Cleveland VA Hospital, Melinta showed that delafloxacin has robust activity against strains of N. gonorrhoeae that have evolved two separate resistance mechanisms against other fluoroquinolones: a) mutations in the target binding site that are known to render ciprofloxacin inactive, and b) efflux mechanisms developed to eject fluoroquinolones. Efflux mechanisms are an adaptation used by bacteria to transport antibiotics through the bacterial membrane out of the cell.

Edward W. Hook III, M.D., professor and chief of the division of infectious diseases at the University of Alabama at Birmingham, added, "Delafloxacin's in-vitro data against ciprofloxacin-resistant strains are encouraging, especially considering the looming public health threat should ceftriaxone-resistant N. gonorrhoeae become widespread."

Complete results from these studies are being presented at the 54^th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), an American Society for Microbiology meeting, being held September 5-9, 2014 at the Washington, DC Convention Center.

Melinta Therapeutics, Inc. is dedicated to the discovery, development and commercialization of groundbreaking antibiotics to overcome drug-resistant, life-threatening infections. The need for new therapies for drug-resistant infections is widely recognized as one of the most serious public-health issues facing the world today. To meet this need, Melinta Therapeutics is rapidly progressing its late-stage investigational antibiotic, delafloxacin, which is currently in Phase 3 development for acute bacterial skin and skin structure infections (ABSSSI) and uncomplicated gonorrhea. Delafloxacin has been designated a qualified infectious disease product (QIDP) for ABSSSI, uncomplicated gonorrhea and community-acquired bacterial pneumonia by the U.S. Food and Drug Administration. A key initiative at Melinta is to develop, through the application of Nobel Prize-winning science, a new class of antibiotics designed to overcome the drug-resistant ESKAPE pathogens known to cause serious hospital-acquired infections. Melinta Therapeutics is privately held and backed by lead investor Vatera Healthcare Partners among others. The company is headquartered in New Haven, CT with offices in Lincolnshire, IL.