When The Medicines Co. (MDCO) gained FDA approval in August 2017 for the antibiotic Vabomere (meropenem and vaborbactam), the win provided clear validation of the approach taken by new company Qpex Biopharma Inc., which has pulled down $33 million in series A money.

U.S. regulators cleared Vabomere to treat adults with complicated urinary tract infections (cUTIs), including pyelonephritis, caused by designated susceptible Enterobacteriaceae – Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae species complex. Vabomere is designed to attack the type of gram-negative bacteria that produce beta-lactamase enzymes that have spread in the U.S. and Europe – particularly the Klebsiella pneumoniae carbapenemase, or KPC, enzyme. KPC-producing bacteria are responsible for most of the carbapenem-resistant Enterobacteriaceae (CRE) in the U.S. and classified by the CDC as an important antimicrobial resistance threat.

Vabomere combines the antibacterial meropenem with the beta-lactamase inhibitor vaborbactam (previously RPX-7009). The agent originally was developed as Carbavance by Rempex Pharmaceuticals Inc., which MDCO acquired in 2013 for $140 million up front and milestones of up to $334 million. Vabomere's approval triggered a payment of $40 million to the former shareholders of Rempex. (See BioWorld Today, Dec. 5, 2013, and Aug. 31, 2017.)

Beta-lactamase inhibitors have reached the market already. Augmentin, from London-based Glaxosmithkline plc, pairs amoxicillin with clavulanate from the class for a variety of infections. Qpex aims for the "sweet spot of resistant gram-negative pathogens that occur in transplant patients," but CEO Michael Dudley noted that superbugs are "beginning to move into other settings than the transplant unit or the intensive care unit. They're in many countries one of the more frequent causes of UTIs in women," he said.

Dublin-based Allergan plc's Avycaz (ceftazidime and avibactam) was launched a couple of years ago, and "rapidly there was resistance reported in the clinic. One needs to be staying ahead of this, and we've been doing that at MDCO over the last four years," he said.

Upon closing of the series A transaction, Qpex, of San Diego, brought aboard preclinical-stage anti-infective assets of Parsippany, N.J.-based MDCO, including beta-lactamase inhibitor technology with a broad spectrum of coverage. Dudley, former chief scientific officer of MDCO, said there has been "a lot of discussion about going after new targets and new chemical classes of drugs. We and others have tried to do that for the last 25 years, but that's highly risky and challenging," he said. "The other approach has been to develop these drugs that aren't antibiotics but can be combined with proven antibiotics" to restore activity lost due to resistance.

"When I was in practice back in the 1980s, one of the things that revolutionized treatment in infections was the availability of oral fluoroquinolones. We lost those tools over the last 15 years. We think there's more on the table here that we can do with these new clinical [beta-lactamase] candidates that we'll be advancing," he told BioWorld. New Enterprise Associates led the financing syndicate and was joined by Adams Street Partners, Lyzz Capital, Hatteras Venture Partners and the Stanford University Draper Fund. More funding comes by way of an agreement with the Biomedical Advanced Research and Development Authority (BARDA).

"The BARDA contract is an outstanding example of a push incentive where BARDA as a partner with us and other companies is sharing the risks of drug development," Dudley said. Qpex has two BARDA deals, the most recent a portfolio agreement that lets the company advance multiple products. "We can move programs in and out of the portfolio according to how the research is taking you" as business and/or public health priorities change, he said. Only four such contracts have been made. The others involved pharma giants GSK, Astrazeneca plc and Pfizer Inc. The previous Qpex contract, signed in 2014, was – like many BARDA deals – specific to a product, in this case Carbavance. In terms of BARDA pacts, "we started behind companies like GSK, Tetraphase and Achaogen, but we got ahead of them and delivered Vabomere as the first approved product," he said.

In November of last year, MDCO, shifting its focus to cardiovascular care, struck a deal with Melinta Therapeutics Inc., of New Haven, Conn., which paid $215 million in cash, plus $55 million in common stock for the business and gained three marketed antibiotics in the deal, including Vabomere. The sale provided MDCO with fresh funds to advance its PCSK9 candidate, inclisiran, through the anticipated completion of pivotal trials and a make-or-break trial readout in the second half of 2019. Melinta benefited by expanding the breadth of its product portfolio with Vabomere, Orbactiv (oritavancin) and intravenous Minocin (minocycline), just as it prepared to launch its own antibiotic, Baxdela (delafloxacin). (See BioWorld, Aug. 10, 2017, and Nov. 30, 2017.)

Inappropriate use of antibiotics is "not good for companies, it's not good for patients and it's not good for clinicians," Dudley said. "But I want to remind everyone that we're not going to save ourselves" simply by cutting back on prescriptions. "Appropriate antibiotic use also can result in resistance."

The initial award from BARDA in 2016 was for $32 million, with up to $100 million more available if all options to extend the partnership are exercised by the agency. The series A money combined with BARDA funds will allow Qpex to "drive these programs deep into development," he said.