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NEWS

CARB-X is funding Summit Therapeutics to develop a new antibiotic to treat multidrug-resistant infections caused by carbapenem-resistant Enterobacteriaceae (CRE)

  • First-in-class antibiotic to treat serious infections caused by pathogens identified as a ‘critical priority’ by the World Health Organization (WHO) and as an ‘urgent threat’ by the US Centers for Disease Control and Prevention (CDC)

(BOSTON) – CARB-X is awarding Summit Therapeutics, (NASDAQ: SMMT) headquartered in Cambridge, MA, USA, with its Discuva subsidiary located in Cambridgeshire, UK, up to US$4.1 million in non-dilutive funding to develop a first-in-class antibiotic to treat multidrug-resistant infections, specifically carbapenem-resistant Enterobacteriaceae (CRE) infections including those caused by serious human pathogens such as Escherichia coli and Klebsiella pneumoniae. Under the award, Summit could receive additional funding of up to $3.7 million from CARB-X if project milestones are achieved, subject to available funds.  The award will help the company progress the SMT-738 antibiotic project through preclinical and Phase 1a clinical development.

“The world urgently needs innovative therapeutics to address life-threatening pathogens that are constantly developing new ways of resisting the effects of antibiotics that are designed to kill them,” said Erin Duffy, R&D Chief of CARB-X, a non-profit global partnership led by Boston University and dedicated to supporting the development of innovative antibiotics, vaccines, diagnostics and other life-saving products to address antibiotic-resistant bacterial infections. “Summit’s SMT-738 represents a novel class that has a new mechanism of inhibition of bacterial cell membrane biosynthesis.  These degrees of novelty combine to offer a potential advantage where antibiotic resistance is concerned.”

“Our mission at Summit is to create patient- and societal-friendly medicinal therapies that improve the quality and duration of patients’ lives, while resolving serious unmet needs,” said Robert W. Duggan, Executive Chairman and Chief Executive Officer of Summit.  “SMT-738 has the potential to save the lives of patients, as yet with untreatable infections through a novel drug class with a low propensity for resistance development.  We are excited and optimistic to take on the real challenge of antibiotic resistance and are grateful to CARB-X for partnering with us in support of this important mission.”

CRE are a family of bacteria that have been dubbed “Nightmare Bacteria” by health officials because they cause deadly infections that are difficult or impossible to treat, and spread rapidly. They can cause bloodstream infections, urinary tract infections, and hospital-acquired pneumonias.  Some strains of multidrug-resistant Enterobacteriaceae are resistant to all existing antibiotics.  CRE bacteria are more likely to emerge in healthcare settings, and infect patients using devices such as catheters or recovering from surgery. In the US, the CDC reports that CRE infections kill an estimated 1,100 patients every year.

Summit’s SMT-738 is the first of a novel class of antibiotics with a new mechanism of action that acts via the LolCDE complex, an essential lipid transport system in Gram-negative bacteria. Combining a novel antibiotic class (SMT-738) with a clinically unexploited target (LolCDE) is thought to mitigate the risk of pre-existing resistance, potentially allowing for the effective treatment of Enterobacteriaceae-related infections that currently have very limited treatment options due to resistance or toxicity of available treatments.

SMT-738 was discovered using Summit’s proprietary technology, the Discuva Platform.  The company expects to begin Phase 1 studies in 2023.

“With the growing threat of antibiotic resistance, particularly with respect to CRE infections, SMT-738 is clearly differentiated from all agents, including the beta-lactamase inhibitors, that are currently used to treat such infections,” adds David Powell, Ph.D., Summit’s Chief Scientific Officer.  “By leveraging the transposon libraries of bacteria within our Discuva Platform, we have identified the target to be the clinically unexploited LolCDE complex, an essential lipid transport system in Gram-negative bacteria.  SMT-738 has potent in vitro activity against clinical CRE isolates including difficult to treat metallo-beta-lactamase carrying strains encoding the New Delhi Metallo-beta-lactamase (NDM).  Having encountered no existing resistance in clinical isolates to the novel chemistry of SMT-738, the ability of our drug molecule to reset the clock against growing resistance is critical in our collective fight against these pathogens causing an urgent public health threat.”

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