Relypsa Loads $80M Series C to Fund Patiromer Phase III

Relypsa Inc. moved patiromer (RLY5016), its high-capacity nonabsorbed oral potassium binder, closer to the finish line in hyperkalemia by closing an $80 million Series C preferred stock financing to fund pivotal Phase III trials and submission of a new drug application (NDA).

The Santa Clara, Calif.-based biotech plans to initiate the Phase III studies this year and to use part of the proceeds to begin planning the drug's commercial launch.

The financing round included broad support from existing investors, including OrbiMed Advisors, 5AM Ventures, New Leaf Venture Partners, Sprout Group, Delphi Ventures and Mediphase Venture Partners, and attracted new investor Sibling Capital LLC.

"It's one of those rare opportunities where we can commercialize patiromer on our own, and we convinced ourselves and our investors that we have the ability to do that," Gerrit Klaerner, Relypsa's president, told BioWorld Today.

The size of the financing also underscored the pace of Relypsa's momentum. The company was formed in 2007 with a $33 million Series A and raised another $70 million in 2010. (See BioWorld Today, Oct. 31, 2007, and Sept. 14, 2010.)

Clinical development has chugged along just as quickly, with patiromer moving from a Phase I to pivotal studies in five years.

Relypsa was spun out from Ilypsa Inc. after it was acquired by Thousand Oaks, Calif.-based Amgen Inc. in July 2007 for $420 million. Relypsa's mission was based on the platform technology and early stage pipeline of Ilypsa, a firm founded in 2003 to develop polymeric drugs designed to improve safety by avoiding absorption into the bloodstream.

Amgen bought privately held Ilypsa primarily to gain rights to ILY101, a phosphate binder that had completed a dose-ranging Phase II study in chronic kidney disease (CKD) patients on dialysis. (See BioWorld Today, June 6, 2007.)

Relypsa's executive team – most of whom made the transition from Ilypsa – has made steady progress in seeking to offer a safer alternative to treating hyperkalemia, which can lead to arrhythmia or sudden cardiac death. The condition often is triggered by drugs that interfere with the kidney's ability to excrete potassium – especially drugs that block the renin-angiotensin-aldosterone system (RAAS), such as angiotensin-converting enzyme inhibitors or aldosterone antagonists.

While RAAS treatments have been shown to reduce deaths in patients with CKD and congestive heart failure (CHF), they can cause potassium retention, resulting in hyperkalemia and limiting their use. Patiromer has been shown to lower serum potassium and prevent hyperkalemia in patients with CKD or congestive heart failure with reduced kidney function, potentially giving prescribers more treatment options.

Patiromer works in the lower gastrointestinal tract, binding to potassium in the colon rather than to dietary potassium. That reduces the amount of free potassium in the colon, causing additional potassium to move from the serum into the colon.

In 2010, Relypsa completed a 104-patient multicenter, randomized, double-blind, placebo-controlled Phase IIb study, PEARL-HF, which showed that RLY5016 significantly reduced the incidence of hyperkalemia in patients with heart failure, compared with placebo.

Patiromer is in an ongoing Phase IIb study, AMETHYST-DN, which in May enrolled the last of 306 patients at approximately 50 sites. The study is evaluating the efficacy of the drug in an initial eight-week treatment period, followed by the long-term evaluation of safety and tolerability in a subsequent 44-week extended treatment period.

In November 2011, the company held an end-of-Phase II meeting with the FDA to gain consensus on patiromer's clinical development plan, including the design of Phase III trials. Based on guidance from that meeting, the company expects the Phase III to be smaller and shorter than AMETHYST-DN, Klaerner said.

Relypsa expects to file the NDA in 2013, seeking a broad label comprising treatment of acute and chronic hyperkalemia regardless of etiology or patient population, and to launch patiromer on its own in early 2014 "in a U.S.-centric strategy, for now," Klaerner said.

In addition to the new funding, the structure is in place to execute the Phase III program and complete regulatory filings, capped by the addition in February of Lance Berman as senior vice president of commercial strategy and medical affairs. Depending on the final details and timetable for patiromer's launch, over the next 24 months to 36 months Relypsa expects to hire a specialty sales force of 50 to 100 reps, targeting nephrologists.

Despite a potential opportunity that Relypsa estimated as more than $1 billion in the U.S., where 1 million patients annually are diagnosed with hyperkalemia, "it's a very focused market, and that's one of the reasons we feel we have the ability to take patiromer to market on our own," said Jim Johnson, the company's senior vice president and chief financial officer.

In the meantime, Relypsa is evaluating additional indications for patiromer and looking toward early human trials for follow-on compound RLY106, which remains in preclinical development.

In other financings news:

• Neuralstem Inc., of Rockville, Md., priced an underwritten public offering of 6 million shares of common stock at 40 cents per share, seeking to raise $2.4 million. The company granted the underwriter a 45-day option to purchase up to an additional 900,000 shares of common stock to cover overallotments, potentially generating another $360,000. The offering is expected to close on or about Aug. 20. Aegis Capital Corp. is acting as sole book-running manager.