Regado Biosciences Inc.'s hefty Series E round on the brink of a Phase III with its anticoagulant REG1 is one of the larger private financings of the year, and the $51 million bets mainly on an approach to clotbusting that the company hopes will get around the bleeding risks that have beset others.

The lead program in arterial thrombosis will test REG1 in percutaneous coronary intervention (PCI) for acute coronary syndrome. A parallel effort is exploring REG1 in open heart surgery, and other applications could include transaortic valve implants.

REG1 therapy involves the Factor IXa inhibitor pegnivacogin, given first for "the maximal physiologic anticoagulation possible," which is "only safe to do because we have a complementary reversal agent" – anivamersen – given at the end of the procedure, said David Mazzo, president and CEO of Basking Ridge, N.J.-based Regado.

"All of the hardware, including the arterial sheath, can be removed immediately without any risk of major bleeding," he said. "With the existing products, like heparin or Angiomax [bivalirudin, the Medicines Co.], at the end of the procedure, they turn off the intravenous drip. And then they have to wait for those products to be metabolized, until the anticoagulation levels get low enough to pull the hardware." REG1, by contrast, is given as a bolus.

The dose of pegnivacogin will be 1 mg/kg, with an 80 percent reversal dose of anivamersen, "which will allow for immediate sheath pull, and a bleeding benefit that we think we will be at least as good as the bleeding benefit afforded by bivalirudin. The additional 20 percent will be given at the discretion of the physician, within a certain period of time, based upon the physiology of the patient and the severity of the disease that's being treated. That's a sort of neat aspect of ours; it incorporates a personalized management approach as well."

A 650-patient Phase IIb study called RADAR tested REG1 against heparin. The Phase III trial, with 13,200 patients at 400 to 500 global sites, will use the same dosing scheme in the same patient population, with the same duration of follow-up, and endpoint, at a cost of about $120 million.

"While we have a substantial amount of cash, we don't have all the cash we need to complete [the trial]," Mazzo told BioWorld Today. "But, given the continued deep pockets of our investors, the interest from potential partners, and the possibility of an initial public offering, we have multiple options for raising the remainder of the money."

Three interim analyses along the way in the two-year trial will provide news flow that could open financial spigots. The trial starts in September of next year. After the first 1,000 patients are enrolled (around the end of the first quarter of 2014) comes the first interim peek. The second will happen after 25 percent enrollment (probably late second or early third quarter of 2014), and the third takes place after half the patients are enrolled (around September 2014). Full data should be available about a year later.

The Series E round was led by new investor RusnanoMedInvest, a subsidiary of the state-run Russian investment firm Rusnano, and included another new, U.S.-based funder, Baxter Ventures. Existing investors Edmond de Rothschild Investment Partners, Domain Associates, Quaker Partners, Aurora Funds and Caxton Advantage Life Sciences Fund also took part.

With Domain and others, the Russian firm put a total of $93 million into U.S. firms, including $21 million for Marinus Pharmaceuticals Inc., of Branford, Conn., and $20.6 million for San Diego-based Lithera Inc.

For Regado, "it all came together at the right time," Mazzo said. "Rusnano's affiliation with Domain helped make the introduction," which was followed by a "fairly lengthy diligence process." Because heart disease and PCI are prevalent in Russia, "it made sense for them on the medical application front and as well as from a financial perspective."

In other financing news:

• Arno Therapeutics Inc., of Flemington, N.J., issued and sold an additional $2.15 million of 8 percent senior convertible debentures and warrants to purchase 14.3 million shares of common stock. Arno previously announced the initial closing of the private placement on Nov. 27, 2012. With the completion of both closings, Arno has sold and issued convertible debentures in the principal amount of $14.9 million and warrants to purchase a total of 99 million shares of common stock. The proceeds from the private placement will support continued development of Arno's oncology pipeline. Arno is conducting clinical and preclinical studies of three drug candidates to treat a variety of cancers.

• MEI Pharma Inc., of San Diego, completed a private placement of common stock and warrants in a financing led by new investors Vivo Ventures and New Leaf Venture Partners. Gross proceeds from the private placement were $27.5 million, before deducting fees and expenses. The company intends to use the net proceeds primarily to advance the clinical development of its lead drug candidate, pracinostat, an oral histone deacetylase inhibitor. The company also effected a 1-for-6 reverse stock split of its common stock, decreasing the number of shares issued and outstanding from about 27.2 million immediately prior to the reverse stock split to about 13.7 million after giving effect to the reverse stock split and the closing of the private placement.

• NeRRe Therapeutics Ltd., of London, raised £11.5 million (US$18.4 million) to develop a portfolio of clinical and preclinical neurokinin receptor antagonists divested from GlaxoSmithKline plc, also of London.