Arixa Pharmaceuticals Completes $8 Million Seed Funding to Initiate Clinical Trial of Oral Avibactam Prodrug to Treat Drug-resistant Gram-negative Infections
Published: May 01, 2018
“The most successful antibiotics have been orally available compounds, such as Augmentin® and Zithromax®; however, there hasn’t been a good, new oral antibiotic for resistant Gram-negative infections in years, and resistance to current agents has become rampant,” stated John Freund, MD, co-founder and Chief Executive Officer of Arixa. “Increasing numbers of Gram-negative infections can no longer be treated orally, and patients must be treated in the hospital or in an outpatient infusion center. Our lead candidate holds promise in addressing this urgent and growing medical need.”
In preclinical, in vivo models, Arixa’s prodrugs of Avibactam have been shown to achieve oral absorption of over 70% in monkeys and 100% in dogs, well above the 30% threshold considered necessary in developing an oral antibiotic. Eric Gordon, PhD, Arixa’s co-founder and Chief Scientific Officer, stated, “Avibactam is a diazabicyclooctane, or ‘DBO’, and we have successfully surmounted the medicinal chemistry obstacles that have previously complicated creating prodrugs for this class of compounds. No oral beta-lactamase inhibitor has been approved since clavulanic acid in 1984, which together with amoxicillin was the BLI component in Augmentin. Importantly, of the projects we are aware of to create novel oral beta-lactamase inhibitors, ours is the only one whose active ingredient is an FDA-approved compound. We are excited with our progress to date and look forward to the potential initiation of our Phase 1 study.”
ARX-1796 is a proprietary prodrug of Avibactam, the first of a new class of BLI’s known as diazabicyclooctanes, or “DBOs”, that offer much broader coverage against beta-lactamase enzymes than clavulanic acid or tazobactam, the previously-approved beta-lactamase inhibitors. Like other BLIs, Avibactam is designed to protect beta lactam antibiotics like penicillins and cephalosporins from being destroyed by enzymes that bacteria produce to defend themselves. Unfortunately, very little of Avibactam is absorbed orally, making it unsuitable for oral administration. Avibactam was approved by the FDA in 2015 as a component in the intravenous-only antibiotic AvyCaz® in combination with the cephalosporin antibiotic ceftazidime.
Arixa’s technology has produced several prodrugs of Avibactam demonstrating oral absorption levels of more than 70% in monkeys and 100% in dogs. Importantly, unlike other programs in development to create novel beta-lactamase inhibitors, Arixa’s prodrugs have been shown to deliver an FDA-approved active ingredient into the bloodstream. The company has filed for broad composition of matter patent claims related to its unique prodrugs.
About Arixa Pharmaceuticals
Arixa Pharmaceuticals™ is developing oral antibiotics for resistant Gram-negative infections, an urgent need. The company’s lead candidate, ARX-1796, is a proprietary orally available prodrug of Avibactam®, a broad spectrum beta-lactamase inhibitor recently approved by the FDA. The company’s technology platform applies unique prodrug chemistry to existing intravenous-only antimicrobial agents to allow their active ingredients to be orally administered. ARX-1796 is anticipated to enter Phase 1 clinical testing in 2019. Arixa was founded by Eric Gordon, a well-known medicinal chemist and antibiotic expert, who founded Versicor/Vicuron, and John Freund, the founder of Skyline Ventures and co-founder of Intuitive Surgical, a $50 billion public company. For more information on Arixa, please visit https://www.arixapharma.com/.
Augmentin® is a trademark of GlaxoSmithKline LLC.
AvyCaz® is a trademark of Allergan, Inc.
Source: Arixa Pharmaceuticals