Summit Presented In Vivo Proof of Concept Data for Targeted Enterobacteriaceae Antibiotics at ASM/ESCMID Conference

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Summit Therapeutics plc  (‘Summit’ or the ‘Company’)

Summit Presents In Vivo Proof of Concept Data for Targeted Enterobacteriaceae Antibiotic at ASM/ESCMID Conference

  • New Mechanism Antibiotic has Potential to Overcome Known Resistance Mechanisms

Oxford, UK, and Cambridge, MA, US, 5 September 2019Summit Therapeutics plc (NASDAQ: SMMT, AIM: SUMM) presented in vivo proof of concept data for its targeted Enterobacteriaceae antibiotics in animal models of sepsis, pneumonia and urinary tract infection ('UTI'). Efficacy data of Summit’s DDS-04 series of antibiotics was comparable to marketed antibiotics in all three disease models. These data were presented in a poster session at the ASM/ESCMID Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance held in Boston, MA, September 3-6, 2019. The findings build on previously reported in vitro studies that showed this new antibiotic class had high potency and specificity for multiple resistant and non-resistant Enterobacteriaceae strains.

“Currently marketed broad-spectrum antibiotics for Enterobacteriaceae infections are failing patients at an increasingly alarming rate due to rising antibiotic resistance,” said Dr David Roblin, President of R&D of Summit. “Our DDS-04 series works via a new mechanism which has the potential to successfully cure patients by overcoming all known bacterial resistance mechanisms. The data presented at ASM/ESCMID show the promise of our DDS-04 series in combatting Enterobacteriaceae infections that we estimate cause more than one million infections annually in the US alone.”

Increasing resistance has rendered many marketed antibiotics ineffective against Enterobacteriaceae. Two Enterobacteriaceae resistance trends seen in the clinic are on the US Centers for Disease Control and Prevention’s list of urgent and serious bacterial threats. Against the backdrop of increasing resistance to current antibiotics, there is a clear need for the development of a new class of antibiotics that could overcome all known resistance liabilities.

Dr Roblin added, “We designed our DDS-04 series of new class antibiotics with the aim of treating infections at all sites where resistance is a clinical issue. That way, we have the chance to make the greatest positive impact on patients. We are extremely excited by the initial proof of concept data our DDS-04 series has shown across sepsis, pneumonia and UTI, and the prospect of moving this series forward.”

The DDS-04 series is undergoing lead optimisation.

Details from the poster presentation:

Sepsis Model

  • Non-neutropenic mouse model (CD-1 mice) infected with E. coli
  • Mice dosed intravenously with DDS-04 series representative three times once every three hours, starting one hour post-infection
  • Tigecycline used as reference, dosed 40mg/kg, two times, once at each of one and six hours post-infection
  • After nine hours, bacterial burden was below the limit of detection in the blood, kidneys, liver, lungs and spleen for both the DDS-04 compound and tigecycline

Pneumonia Model

  • CD-1 mice infected with K. pneumoniae
  • Mice dosed intravenously with DDS-04 series representative three times, once every eight hours, starting two hours post-infection
  • Tigecycline used as reference, dosed 40mg/kg, three times daily every eight hours subcutaneously
  • After 26 hours, a 4.5 log10 reduction in bacterial burden was observed in the lungs for the DDS-04 compound and a similar reduction was observed with tigecycline

UTI Model

  • C3H/HeN female mice were infected with E. coli
  • Mice dosed intravenously with DDS-04 series representative three times daily every eight hours over three days
  • Ciprofloxacin used as reference, dosed 10mg/kg, three times daily every eight hours over three days
  • On day four, a significant reduction in bacterial burden was observed in the urine, bladder and kidneys for both the DDS-04 compound and ciprofloxacin

About DDS-04The DDS-04 series comprises 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 has also shown a low propensity for resistance development and did not show cross-resistance with existing classes of antibiotics, suggesting the DDS-04 series has the potential to overcome known resistance mechanisms. This profile makes the DDS-04 series attractive for further development for the treatment of Enterobacteriaceae infections.

About EnterobacteriaceaeEnterobacteriaceae 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.

Contacts

Summit    
Glyn Edwards / Richard Pye (UK office) Tel: 44 (0)1235 443 951
Michelle Avery (US office)   +1 617 225 4455
     
Cairn Financial Advisers LLP (Nominated Adviser) Tel: +44 (0)20 7213 0880
Liam Murray / Tony Rawlinson    
     
N+1 Singer (Joint Broker) Tel: +44 (0)20 7496 3000
Aubrey Powell / Jen Boorer, Corporate FinanceTom Salvesen, Corporate Broking    
     
Bryan Garnier & Co Limited (Joint Broker) Tel: +44 (0)20 7332 2500
Phil Walker / Dominic Wilson      
MSL Group (US) Tel: +1 781 684 6557
Jon Siegal   summit@mslgroup.com
     
Consilium Strategic Communications (UK) Tel: +44 (0)20 3709 5700
Mary-Jane Elliott / Sue Stuart / Sukaina Virji /   summit@consilium-comms.com
Lindsey Neville    

Summit Forward-looking Statements

Any statements in this press release about the Company’s future expectations, plans and prospects, including but not limited to, statements about the clinical and preclinical development of the Company’s product candidates, the therapeutic potential of the Company’s product candidates, the potential commercialisation of the Company’s product candidates, the sufficiency of the Company’s cash resources, the timing of initiation, completion and availability of data from clinical trials, the potential submission of applications for marketing approvals and other statements containing the words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials or preclinical studies will be indicative of the results of later clinical trials, expectations for regulatory approvals, laws and regulations affecting government contracts and funding awards, availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the "Risk Factors" section of filings that the Company makes with the Securities and Exchange Commission, including the Company’s Annual Report on Form 20-F for the fiscal year ended 31 January 2019. Accordingly, readers should not place undue reliance on forward-looking statements or information. In addition, any forward-looking statements included in this press release represent the Company’s views only as of the date of this release and should not be relied upon as representing the Company’s views as of any subsequent date. The Company specifically disclaims any obligation to update any forward-looking statements included in this press release.

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