DUBLIN – Antibiotics developer Venatorx Pharmaceuticals Inc. raised $42 million in a series B round that will fund a registration trial of its lead program, VNRX-5133, which it has penciled in for the first half of next year.

It's a big leap for this little-known company, given that the therapy is still undergoing a phase I trial in healthy volunteers. But one component of VNRX-5133 is a known entity.

The Malvern, Pa.-based company is refining a decades-old strategy by pairing a novel broad-spectrum beta-lactamase inhibitor (BLI) with an approved beta-lactam antibiotic.

Venatorx has operated under the radar for the last eight years, but its founders include a trio of old industry hands: CEO Christopher Burns, Chief Development Officer Luigi Xerri and Senior Vice President of Biology Daniel Pevear. They previously led Protez Pharmaceuticals, a company focused on the problem of methicillin-resistant Staphylococcus aureus, to an acquisition by Basel, Switzerland-based Novartis AG in a deal worth up to $400 million. (See BioWorld Today, June 5, 2008.)

The main focus at Venatorx is on a treatment concept that dates back to the 1970s, when the first BLI, clavulanic acid, was introduced to prevent bacterial hydrolysis of beta-lactam antibiotics. Some newer variations on that theme include Avycaz (ceftazidime/avibactam) and Zerbaxa (ceftolozane/tazobactam), which are marketed, respectively, by London-based Astrazeneca plc and Dublin-based Allergan plc, and by Merck & Co. Inc., of Kenilworth, N.J.

Avycaz gained approval in February 2015 for treating complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI), including pyelonephritis (kidney infection). Zerbaxa was licensed in December 2014 for the same indications. Each has their shortcomings, however. Avibactam is active against class A and class C and some class D beta-lactamases, according to a paper published by Astrazeneca scientists in the October 2014 issue of Antimicrobial Agents and Chemotherapy. Tazobactam is active against some class A and class C enzymes but not against serine carbapenamases or metallo-beta-lactamases, according to Zerbaxa's FDA label.

Venatorx aims to extend the treatment concept further, by introducing a novel BLI that can selectively target the four major beta-lactamase classes. "No one's been able to come up with a product that can directly inhibit all four classes," CEO Burns told BioWorld.

His team has not yet reported any data in the scientific literature, but it has received ongoing grant support from the NIH and the Wellcome Trust in London to develop a series of compounds that are highly selective for a structurally diverse set of beta-lactamases but which do not hit mammalian enzymes.

"We've always been biased toward a chemistry-based approach rather than a screening-based approach," Burns said. "I think the key thing for us was to understand that multiple classes of enzyme were able to recognize the same substrate, which is beta-lactam."

Combating drug-resistant bacteria by discovering novel targets has been a challenge for other firms – given the apparent ease with which bacteria can "brush off" new agents. VNRX-5133 is being developed to tackle carbapenem-resistant Enterobacteriaceae and carbapenem-resistant Pseudomonas – its main indications are cIAI and cUTI, but the company will also conduct an open-label study in patients with multidrug-resistant infection.

It is not yet disclosing the beta-lactam component of the therapy. About one year behind is VNRX-7145, an oral combination of a BLI and beta-lactam antibiotic, which is currently nearing an IND filing. The company's third major program comprises a new antibiotic class that targets cell wall biosynthesis.

The current round was led by Versant Ventures, of San Francisco, with participation from London-based Abingworth and Foresite Capital, also of San Francisco.

The investment is one of several that antibiotics developers have secured this year. Others raising cash include Dublin-based Iterum Therapeutics Ltd., which took in $65 million to fund phase III development of sulopenem, an oral antibiotic for treating multidrug-resistant infections. Polyphor Ltd., of Allschwil, Switzerland, raised CHF40 million (US$42.3 million) to fund development of murepavadin for treating hospital-acquired pneumonia caused by Pseudomonas aeruginosa infection. And Cambridge, Mass.-based Spero Therapeutics LLC raised $51.7 million in a C round to progress development of a diverse pipeline.

"Antibiotics is a space that has come in and out of fashion," Versant partner Carlo Rizzuto told BioWorld. It has been an area of ongoing interest to Versant, he said, given the significant unmet need, but much of the industry pipeline has failed to excite. "We've been looking for the innovators," Rizzuto said. In Venatorx, he said, Versant believes it has uncovered "a hidden gem."

Rizzuto and Abingworth's Shelley Chu have joined the company's board.