Summit Therapeutics plc (LSE:SUMM; NASDAQ:SMMT) identified two new types of narrow-spectrum antibiotics targeting new Neisseria gonorrhoeae targets that could help treat gonorrhea.
Summit presented its findings at the American Society for Microbiology Microbe (ASM Microbe) conference in Atlanta.
The incidence of N. gonorrhoeae resistance to existing antibiotics is increasing, suggesting a need for new classes of antibacterial therapies.
Using its Discuva platform, a transposon mutagenesis and bioinformatics-based system, Summit identified two new N. gonorrhoeae targets and bactericidal compounds dubbed SMT-571 and the DDS-03 series against those targets.
Summit found that the DDS-03 compounds act through N. gonorrhoeae electron transfer flavoprotein subunit A (N. gonorrhoeae ETF A), ETF B and ETF D. Summit COO David Roblin declined to disclose SMT-571's target.
Against N. gonorrhoeae clinical isolates from a World Health Organization panel, the minimum inhibitory concentration (MIC) of SMT-571 was 0.09 μg/mL and the MIC of DDS-03a, one of the DDS-03 series compounds, was 0.001-0.002 μg/mL. DDS-03b inhibited growth of a panel of 96 N. gonorrhoeae clinical isolates from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) with an MIC of 0.01 μg/mL.
Additionally, DDS-03c was effective against isolates of N. gonorrhoeae and N. meningitidis but not species from other bacterial genera, suggesting the compound has narrow spectrum activity.
Summit said SMT-571 and the DDS-03 compounds had favorable toxicity profiles in hemolysis and cytotoxicity assays and favorable pharmacokinetic profiles in mice. SMT-571 had an oral bioavailability of 96% and a maximum plasma concentration of 3017 ng/mL.
Summit plans to conduct IND-enabling studies of SMT-571 in 2H18, and Roblin told BioCentury that the company plans to start clinical trials in 2019.
Summit acquired the Discuva technology through its takeout of antibiotic company Discuva Ltd. (Cambridge, U.K.) in January.