Resistance really is futile

European partnership aims to re-enable antibiotics against resistant bacteria

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HARLOW, United Kingdom—U.K.-based drug discovery servicescompany Argenta and French biopharmaceutical startup ANTABIO have announced acollaboration agreement geared toward identifying and developing compoundsaimed at countering resistance to common antibacterial agents.
Under the terms of the agreement, Argenta will offer itsintegrated drug discovery expertise and provide medicinal chemistry,computer-aided drug design and ADME/PK services to assist ANTABIO in theidentification of novel antibacterial agents and discovery of a developmentcandidate that can be progressed into clinical trials.
ANTABIO brings to the table its disease-area expertise inthe antibacterial field, as well as specific in-vitro assays that will be central to the discovery process.
The collaboration is funded by a Wellcome Trust Seeding DrugDiscovery award that provides about $6 million of funding over three years.
Alarmingly, drug resistance prevalence is growing worldwide,leaving researchers looking for new mechanisms to combat drug-resistantbacteria. Multidrug-resistant, Gram-negative bacteria account for mosthospital-acquired infections today. One of the most effective treatments is theuse of carbapenem antibiotics. However, their usefulness is becomingincreasingly compromised due to the rise of clinical resistance associated withthe spread of genes encoding various metallo ß-lactamase (MBL) enzymes.
The primary goal of this collaboration will be to develop asafe and effective pan-inhibitor of bacterial MBL enzymes, and to develop thesefrom current leads to preclinical candidate nomination. The research will alsoapply to developing compounds that will prevent infections caused by virulentand multidrug-resistant bacteria, including Escherichia coli (E. coli), that are responsible for severe hospital-acquiredinfections as well as other common conditions such as urinary tract infectionsand food poisoning.
"The drugs that we will develop will be co-administered witha carbapenem, thereby returning carbapenems to full clinical effectiveness,"says Marc Lemonnier, CEO of ANTABIO. "A feature of this paradigm is that oralactivity is not required—carbapenems are dosed intravenously, as would be theMBL inhibitor. This regimen simplifies the research and greatly increases thepossibilities for success."
In the United States and Europe, drug-resistant bacterialinfections are responsible for up to 75,000 deaths per year and 2.5 millionadditional days spent in the hospital at an average cost to the healthcaresystem of about $2 billion. The World Health Organization has identifiedinfections caused by drug-resistant bacteria as a disease requiring priorityattention and novel medicines.
"The medical need for MBL inhibitors remains critical," saysLemonnier. "A successful drug will alleviate patient suffering and reduceantibiotic failure in the clinic."
This antibacterial collaboration between Argenta and ANTABIOwill not be the first joint venture between the two organizations. Keyleadership at both companies have known each other for some time, and theorganizations have collaborated at a low level on smaller projects before fortwo or three years, says John Montana, managing director of Argenta.
"We talked(ANTABIO's leadership) into trying to get Wellcome Trust grant funding," saysMontana.
The Wellcome Trust is a global charitable foundationdedicated to achieving improvements in human and animal health throughbiomedical research and the medical humanities. It operates independently ofpolitical and commercial interests.
"ANTABIO strongly believes that partnering with the mostoutstanding players in the drug discovery arena will be key in advancing novelsolutions to defeat treatment failure," Lemonnier said in a statement on theANTABIO website. "We are proud to have the support of the Wellcome Trust onthis exciting discovery program whose success will benefit patients sufferingfrom severe bacterial infections."
"Getting projects into the right state to attract grantfunding hasn't been exploited well," says Montana. "Argenta decided to adoptthis strategy a few years ago, facilitating academic and small companies tomake use of the grant opportunities that are available."
Argenta is currently working on three such majorpartnerships: this antibacterial endeavor with ANTABIO, a collaboration withthe University of Cambridge in pain and a third partnership that is expected tobe formally announced to the public in the coming month.

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