Summit Therapeutics plc
(‘Summit’ or the ‘Company’)
Summit’s DDS-04 Enterobacteriaceae Programme Demonstrates In Vivo Efficacy in Sepsis and Pneumonia
Oxford, UK, and Cambridge, MA, US, 9 July 2019 – Summit Therapeutics plc (NASDAQ: SMMT, AIM: SUMM) today announces that it has demonstrated the potential of its DDS-04 series of new class antibiotics as an Enterobacteriaceae-targeted treatment through in vivo proof of concept data in sepsis and pneumonia animal models. These data build on the previously published proof of concept preclinical study for DDS-04 in urinary tract infections. Enterobacteriaceae are a family of Gram-negative bacteria that cause severe and often deadly infections.
“There is a great need to advance truly differentiated treatments for Gram-negative bacteria, where there have been no new classes of antibiotics discovered since the last century. In particular, the rise of untreatable and hard to treat Enterobacteriaceae infections is a frightening prospect,” said Dr David Roblin, President of R&D of Summit. “Our potential solution is DDS-04, a series of Enterobacteriaceae-targeted antibiotics for the treatment of resistant and non-resistant bacteria.”
In the sepsis infection model, mice were infected with E. coli. Intravenous treatment with a representative compound of the DDS-04 series cured the infection. For the pneumonia infection model, mice were infected with K. pneumoniae. Intravenous treatment with a representative compound of the DDS-04 series resulted in a significant reduction in bacterial burden in the lungs. Summit’s preclinical data indicate that DDS-04 compounds have the potential to treat Enterobacteriaceae infections in all three key infection sites of urinary tract, bloodstream and lung. However, it is the latter two where there is the greatest unmet patient need. Further details are expected to be published at an upcoming scientific meeting.
Dr Roblin added, “DDS-04 aligns with our strategy of targeting pathogenic bacteria and seeking to preserve patients’ good bacteria known to play an important role in overall patient health. Importantly, pathogen-targeted antibiotics could be a new front-line treatment to support good stewardship with broad-spectrum antibiotics being reserved.”
Today, Enterobacteriaceae infections are treated with a range of broad-spectrum antibiotics, where there is a high risk of treatment failure due to antibiotic resistance. Further, multi-drug resistance occurs in many of the severe hospital-acquired Enterobacteriaceae infections. Patients who receive multiple rounds of broad-spectrum antibiotics to treat these infections have increased risk for added complications, including C. difficile infection. A targeted, new class of antibiotics could have the benefit of not only being able to kill all strains of Enterobacteriaceae, regardless of resistance, but also could have the potential to preserve patients’ microbiomes.
The DDS-04 series is undergoing lead optimisation.
The DDS-04 series are targeted-spectrum compounds that act via a novel bacterial target, LolCDE. With its new mechanism of action, the DDS-04 series was rapidly bactericidal and highly potent across globally diverse Enterobacteriaceae strains in research studies, which included multi-drug resistant isolates. Importantly, the DDS-04 series also showed low propensity for resistance development and did not show cross-resistance with existing classes of antibiotics, suggesting that DDS-04 compounds have the potential to overcome known resistance mechanisms. This profile makes the DDS-04 series attractive for further development for the treatment of Enterobacteriaceae infections.
Enterobacteriaceae are a family of Gram-negative bacteria responsible for severe and often deadly infections. They account for a significant fraction of cases across conditions, including bloodstream infections, hospital-acquired pneumonias and complicated urinary tract infections. Summit estimates there are more than 1 million infections in the US annually caused by Enterobacteriaceae across these three settings. Increasing resistance of Enterobacteriaceae has rendered many marketed antibiotics ineffective against these bacteria. Two of the most alarming antibiotic resistance trends are extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and carbapenem-resistant Enterobacteriaceae (CRE). ESBL is an enzyme that allows bacteria to become resistant to a wide variety of penicillin and cephalosporin antibiotics. CRE are resistant to nearly all existing antibiotics, including carbapenems which are considered the antibiotics of last resort.
About Summit Therapeutics
Summit Therapeutics is a leader in antibiotic innovation. Our new mechanism antibiotics are designed to become the new standards of care for the benefit of patients and create value for payors and healthcare providers. We are currently developing new mechanism antibiotics for infections caused by C. difficile, N. gonorrhoeae and ESKAPE pathogens and are using our proprietary Discuva Platform to expand our pipeline. For more information, visit www.summitplc.com and follow us on Twitter @summitplc.
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