In another savvy acquisition for The Medicines Co., the Parsippany, N.J.-based firm nabbed 2-year-old antibiotics developer Rempex Pharmaceuticals Inc., gaining rights to a marketed product that should help lay the groundwork for the commercial launch of its own oritavancin antibiotic, anticipated next year, and a Phase III-ready combination beta-lactamase inhibitor/carbapenem candidate with blockbuster potential.

The deal also brings earlier-stage programs targeting antibacterial resistance, particularly in cases of gram-positive pathogens, with an aim at treating serious and multidrug-resistant infections in hospitalized patients. As Medicines Chairman and CEO Clive Meanwell put it: “We’re in infectious diseases in the hospital, and we’re here to stay.”

Terms of the potential $434 million deal call for Medicines to pay $140 million up front to Rempex equity holders, with milestones totaling up to $334 million – $214 million associated with development and regulatory events and $120 million linked to commercial achievements.

The initial payment is almost twice the venture capital raised by Rempex, of San Diego, which was formed in 2011 to acquire the non-Aeroquin assets from predecessor Mpex Pharmaceuticals Inc. following Mpex’s acquisition by Aptalis Pharma Inc. Launched with an initial $8.5 million Series A, Rempex closed a $67.5 million Series B round from investors Frazier Healthcare Ventures, Vivo Ventures, SV Life Sciences, Orbimed Advisors and Adams Street Partners. (See BioWorld Today, Nov. 10, 2011.)

Last year, Rempex added to its portfolio Minocin IV (minocycline for injection), which is marketed in the U.S. for resistant infections due to Acinetobacter, a pathogen that’s particularly prevalent in intensive care units. It’s the only marketed minocycline in the U.S.

“It’s a unique case,” Rempex’s president and CEO, Dan Burgess, explained to investors during the Wednesday conference call to announce the deal. He described minocycline as an “old drug” that had been pulled from shelves years ago simply because there was no need for a treatment for drug-resistant Acinetobacter infections.

But that changed in recent years, with the Department of Defense declaring Acinetobacter resistance a problem and demanding that minocycline be supplied as needed. But it was never actively promoted, and has recorded minimal sales, roughly $1 million per year.

“No one know it’s out there,” Burgess said. He added that Rempex has been “looking for the right partner to help us launch” in the U.S.

Medicines will take over those launch initiatives, during which it will reach out to many of the same providers and prescribers for oritavancin, a semisynthetic lipoglycopeptide antibiotic that met its endpoint in a confirmatory Phase III study earlier this year.

Oritavancin, which Medicines acquired in its 2009 buyout of Targanta Therapeutics Inc. following the drug’s troubled development history, is expected to be the subject of a new drug application later this year, with the company seeking approval in acute bacterial skin and skin structure infections. (See BioWorld Today, Jan. 14, 2009, and July 3, 2013.)

Meanwhile, Medicines will continue work on an improved version of Minocin, RPX602, for which it hopes to gain approval next year under a supplemental new drug pathway. If all goes well, the company’s hospital infection sales team would be launching both oritavancin and the revamped Minocin in 2014.

Blockbuster Potential

While Minocin offers an immediate revenue opportunity for Medicines, it’s Rempex’s late-stage Carbavance program that gained most of the attention during Wednesday’s investor call. Aimed at overcoming the resistance that has built up over the years with widely used carbapenem, Carbavance adds beta-lactase inhibitor (BLI) RPX7009. That component is designed to inhibit Klebsiella pneumonia carbapenemases, the enzyme that acts as the primary resistance mechanism to carbapenems.

Basically, “it restores the usefulness” of carbapenem, explained Jeff Loutit, Rempex’s chief medical officer.

The use of combo products to battle antibiotic resistance isn’t new. Glaxosmithkline’s Augmentin, for instance, combines penicillin with BLIs and has recorded about $2 billion per year in sales. Pfizer Inc.’s Zosyn, a first-generation BLI (tazobactam) with piperacillin, generates about $1 billion in sales. But Carbavance could be the first combo product involving carbapenem, a familiar and safe drug in the infection disease arsenal.

“Physicians have relied on these drugs for many years,” noted Michael Dudley, Rempex’s chief scientific officer.

More importantly, the rise in carbapenem-resistant infections, notably Enterobacteriaceae, has been identified by the Centers for Disease Control and Prevention as one of the most deadly gram-negative pathogens. (See BioWorld Today, April 22, 2013.)

Rempex had completed Phase I dose-escalation studies, and Medicines plans to take Carbavance into two “modest” registrational trials next year. Loutit said specific trial designs were still in the works, but the firm expects one to be a noninferior study against a standard drug in patients with complicated urinary tract infections. The second trial likely would involve carbapenem-resistant subjects with a range of infectious diseases.

Assuming positive data from both trials, Carbavance could be on the market as early as 2017.

“New drugs targeting gram-negative infections are largely expected to be blockbusters,” RBC Capital Markets analyst Adnan Butt wrote in a research note. “Furthermore, the new gram-negative pipeline will be synergistic with [Medicines’] infrastructure for oritavancin.”

Expanding Portfolio

Its acquisition of Rempex also brings Medicines a preclinical portfolio and an ongoing discovery program to identify additional BLI-based combination products for overcoming resistance mechanisms such as extended-spectrum beta-lactamase, serine carbapenemase and metallo beta-lactamase production in gram-negative organisms.

Medicines’ focus will continue on the hospital market. Its hospital infectious disease pipeline is one of three focus areas, along with acute cardiovascular care and surgery and perioperative care. The company already markets anticoagulant Angiomax (bivalirudin), hypertension therapy Cleviprex (clevidipine) and Recothrom (thrombin topical [recombinant]), a drug-device combo product for non-arterial bleeding during surgery.

The company has built up its portfolio through select acquisition and licensing deals over the years. In addition to oritavancin, it gained rights to intravenous antiplatelet candidate cangrelor under a 2003 license agreement with Astrazeneca plc. After a couple of clinical stumbles, Medicines completed Phase III testing, and cangrelor currently is under FDA review for use in patients undergoing percutaneous coronary intervention and those who require bridging from oral antiplatelet therapy to surgery.

Its 2012 buyout of Incline Therapeutics Inc. added rights to Ionsys, a patient-controlled analgesia system for short-term management of acute postoperative pain in the hospital setting. (See BioWorld Today, Dec. 13, 2012.)

Earlier this year, Medicines joined up with Alnylam Pharmaceuticals Inc., paying the RNAi expert $25 million up front for its candidate targeting PCSK9. (See BioWorld Today, Feb. 5, 2013.)

The firm will update financial guidance during its next quarterly call. As of Sept. 30, it had about $462.4 million in cash and equivalents.

Shares of Medicines (NASDAQ:MDCO) gained $1.15 to close Wednesday at $37.70.