Summit Presents Positive New Preclinical Data on Novel CDI

OXFORD, United Kingdom, June 05, 2017 (GLOBE NEWSWIRE) -- Summit Therapeutics plc (NASDAQ: SMMT ) (AIM:SUMM), the drug discovery and development company advancing therapies for Duchenne muscular dystrophy and Clostridium difficile infection (‘CDI’), announces new preclinical data on ridinilazole, a novel and highly selective antibiotic for the treatment of CDI, were presented at ASM Microbe 2017 that was held in New Orleans, US from 1-5 June 2017.

“These positive preclinical data presented at ASM Microbe highlight the potency of ridinilazole against a wide range of C. difficile clinical isolates from patients with CDI,” commented Dr David Roblin, President of Research and Development of Summit. “Combining potency and selectivity, ridinilazole has shown positive results in clinical trials that support its potential to treat patients with CDI and reduce the rate of recurrent disease. It is thought that the preservation and restoration of the patient microbiome is important in reducing recurrence and ridinilazole’s narrow spectrum is designed to achieve this. We believe ridinilazole has the potential to be a novel, and urgently needed, front-line treatment option for this serious disease.”

The results were detailed in two poster presentations given by L.A. McDermott and E. Bassères, respectively. Summaries of the presentations are as follows:

In-vitro Activity of Ridinilazole and Comparators against Isolates of Clostridium difficile Obtained from Stools of Patients as Part of US surveillance in 2014 DR Snydman, LA McDermott, CM Thorpe, J Chang, J Wick, SG Jenkins, EJC Goldstein, R Patel, BA Forbes, S Johnson, D Gerding, ST Walk  and R Vickers This study, funded by Summit, assessed ridinilazole against 200 clinical isolates of C. difficile collected from toxin positive stool samples during 2014 as part of a US surveillance programme. The results showed that ridinilazole was very active against all C. difficile isolates with overall minimum inhibition concentrations (MIC) distributed over a very narrow range of 0.12 to 0.5 µg/mL. Based on the MIC ₉₀ of 0.25 mg/mL, ridinilazole was more potent than vancomycin and metronidazole, two antibiotics commonly prescribed to treat CDI. Ridinilazole also maintained activity against 027 hypervirulent strains of C. difficile and retained activity against C. difficile isolates resistant to common antibiotics moxifloxacin, clindamycin, vancomycin and imipenem.

In vitro Selection of Clostridium difficile Resistance Mutants Exposed to Ridinilazole E. Bassères, T. Rashid, B. Endres, M. Alam, R. Vickers, and KW. Garey This in vitro study, also funded by Summit, was designed to understand the effects of ridinilazole on resistance development and further elucidate the mechanism of action of this highly potent yet selective antibiotic for the treatment of CDI. A low-level, stable ridinilazole mutant resistant strain was developed after multiple sub-MIC passages and this mutant will be used in future preclinical studies on mechanism of action.

Copies of the presentations given at ASM Microbe 2017 are available from the ‘Programmes’ section of Summit’s website, www.summitplc.com .

Ridinilazole successfully completed a Phase 2 proof of concept clinical trial where it demonstrated statistical superiority against vancomycin in sustained clinical response, an endpoint defined in the clinical trial as clinical cure at the end of treatment and no recurrence of CDI within 30 days of the end of therapy. Ridinilazole is currently being prepared for Phase 3 clinical trials, which are planned to commence during the first half of 2018.

About  C. difficile  Infection C. difficile  infection is a serious healthcare threat in hospitals, long-term care homes and increasingly the wider community with over one million estimated cases of CDI each year in the United States and Europe. It is caused by an infection of the colon by the bacterium  C. difficile , which produces toxins that cause inflammation and severe diarrhoea, and in the most serious cases can be fatal. Patients typically develop CDI following the use of broad-spectrum antibiotics that can cause widespread damage to the natural gastrointestinal (gut) flora and allow overgrowth of  C. difficile  bacteria. Existing CDI treatments are predominantly broad spectrum antibiotics, and these cause further damage to the gut flora and are associated with high rates of recurrent disease. Recurrent disease is the key clinical issue as repeat episodes are typically more severe and associated with an increase in mortality rates and healthcare costs. The economic impact of CDI is significant with one study estimating annual acute care costs at $4.8 billion in the US. 

About Ridinilazole Ridinilazole is an orally administered small molecule antibiotic that Summit is developing specifically for the treatment of CDI. In preclinical efficacy studies, ridinilazole exhibited a narrow spectrum of activity and had a potent bactericidal effect against all clinical isolates of  C. difficile  tested. In a Phase 2 proof of concept trial in CDI patients, ridinilazole showed statistical superiority in sustained clinical response ('SCR') rates compared to the standard of care, vancomycin. In this trial, SCR was defined as clinical cure at end of treatment and no recurrence of CDI within 30 days of the end of therapy. Ridinilazole has received Qualified Infectious Disease Product ('QIDP') designation and has been granted Fast Track designation by the US Food and Drug Administration. The QIDP incentives are provided through the US GAIN Act and include an extension of marketing exclusivity for an additional five years upon FDA approval.

About Summit Therapeutics Summit is a biopharmaceutical company focused on the discovery, development and commercialisation of novel medicines for indications for which there are no existing or only inadequate therapies. Summit is conducting clinical programs focused on the genetic disease Duchenne muscular dystrophy and the infectious disease C. difficile infection. Further information is available at www.summitplc.com  and Summit can be followed on Twitter (@summitplc).

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Forward-looking Statements Any statements in this press release about Summit’s future expectations, plans and prospects, including but not limited to, statements about the clinical and preclinical development of Summit’s product candidates, the therapeutic potential of Summit’s product candidates, and the timing of initiation, completion and availability of data from clinical trials, 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 on-going 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, availability of funding sufficient for Summit’s foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the "Risk Factors" section of filings that Summit makes with the Securities and Exchange Commission, including Summit’s Annual Report on Form 20-F for the fiscal year ended January 31, 2017. 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 Summit’s views only as of the date of this release and should not be relied upon as representing Summit’s views as of any subsequent date. Summit specifically disclaims any obligation to update any forward-looking statements included in this press release.

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