Just five years after its founding and after raising approximately $100 million across four venture rounds, ZS Pharma Inc. followed the well-trod path toward an initial public offering (IPO), where it will seek to raise up to $86 million. The Coppell, Texas-based firm has a single asset, ZS-9, designed to treat hyperkalemia, a life-threatening condition that affects patients with chronic kidney disease (CKD), hypertension, diabetes and/or chronic heart failure (CHF).
ZS closed a $55 million series D in March, telling BioWorld Today at the time that CEO Robert Alexander and president Al Guillem were not elaborating on the development timetable and commercialization strategy for its ion-trap therapy. Instead, the company is letting its S-1 statement do the talking.
ZS-9 is a microporous, fractionated, protonated zirconium silicate designed to selectively bind and remove potassium, providing a mechanism to treat hyperkalemia without affecting other electrolytes. The company's first-in-man phase II study, ZS002, was completed in May 2012, followed by an initial phase III study, ZS003, completed in November 2013. Both trials met their pre-specified primary and secondary efficacy endpoints with statistical significance. Those included change in serum potassium levels from baseline during the first 48 hours, after administering ZS-9 three times a day, and identification of an optimal dose to normalize serum potassium levels (3.5 to 4.9 mmol/l) without causing serious adverse events.
The ZS003 study, which enrolled 750 adults with mild to moderate hyperkalemia, also evaluated change in serum sodium, magnesium, calcium and blood urea nitrogen from baseline during the first 48 hours after administering ZS-9 three times a day, according to Thomson Reuters Cortellis Clinical Trials Intelligence. In the acute portion of the phase III trial, 99 percent of patients were normokalemic after receiving 10 grams of ZS-9 three times a day for 48 hours. The extended portion of the trial demonstrated that reductions achieved in the acute phase could be maintained using 5 g or 10 g of ZS-9 administered once daily. In comparison, patients on placebo saw potassium levels revert to near pretreatment levels.
ZS-9 showed a favorable safety profile and was well tolerated across populations that included patients with CKD, HF and diabetes and those taking renin-angiotensin-aldosterone-system (RAGAS) therapy. The most common adverse events were mild to moderate gastrointestinal symptoms, including nausea, vomiting, constipation and diarrhea, which occurred at similar rates and severity as placebo. No serious adverse events were attributed to ZS-9.
A second phase III study (ZS004) is under way. The global multicenter, multidose, prospective trial is enrolling patients with hyperkalemia (potassium levels > 5 mEq/L), including those with CKD, HF and diabetes, and those on RAAS therapy. In the open-label induction phase, approximately 275 patients will receive 10 g of ZS-9 administered three times daily for 48 hours. Patients who achieve normokalemia are eligible to be randomized in a double-blind fashion to one of three doses of ZS-9 (5 g, 10 g or 15 g) or placebo administered once daily for 28 days.
The primary efficacy endpoint of ZS004 is the mean serum potassium level of each ZS-9 treatment group compared with that of placebo.
In conjunction with ZS004, ZS Pharma also will conduct ZS004E, an extension study designed to generate longer-term open-label safety, tolerability and efficacy data in patients who participated in ZS004. In ZS004E, patients will receive up to an additional 60 days of treatment, resulting in a combined potential of 90 days of treatment with ZS-9 over the course of both studies.
In addition, the company expects to initiate a long-term safety study (ZS005) in the second quarter.
TOE TO TOE WITH PATIROMER?
ZS004 data are expected to report by year-end. Provided the study confirms earlier findings, ZS Pharma plans to submit a new drug application (NDA) to the FDA and a marketing authorization application to the EMA in the first half of 2015. The company intends to go to market alone in the U.S., indicating in its SEC filing that proceeds from the IPO will be used for regulatory filings, manufacturing scale-up to support commercial launch, pre-commercialization marketing activities and the development of a U.S. specialty sales force targeting nephrologists and non-interventional cardiologists. ZS plans to strike one or more commercial deals for ZS-9 outside the U.S.
The company holds multiple patents on the ZS-9 formulation, providing exclusivity to at least 2032, according to Cortellis.
In its S-1, ZS reported $23.8 million in cash and equivalents and an accumulated deficit of $60.8 million as of March 31. The company said 29.8 million common shares were outstanding. The company's investors include Adage Capital, Alta Partners, Devon Park Bioventures, Novo A/S, RA Capital, Rivervest Venture Partners, Salem Partners, Sofinnova Ventures and 3x5 Special Opportunity Partners.
Filing as an emerging growth company, ZS Pharma plans to list on Nasdaq as ZSPH. J.P. Morgan and Credit Suisse are joint bookrunners on the deal, which is not yet priced.
In its filing, ZS maintained that its primary competition is Relypsa Inc., which also is racing to market with a phase III candidate, patiromer, for hyperkalemia. Indeed, the two biotechs are the only companies directly targeting hyperkalemia.
Relypsa filed for its IPO at the end of September 2013 and closed the offering two months later, pricing 7.8 million shares at $11 apiece to garner $85.8 million. (See BioWorld Today, Oct. 1, 2013, and Nov. 18, 2013.)
Last month, the Redwood City, Calif.-based firm topped off its IPO proceeds by adding another $101 million through a public offering of 4.1 million shares, including overallotments, at $24.50 apiece. Last week, Relypsa disclosed, in conjunction with its first quarter financial results, that it expects to file its NDA for patiromer in the third quarter, following a successful meeting with the FDA to review results from its clinical program and discuss a potential product label.
On Thursday, with the broader market rocked by disappointing economic news, Relypsa's shares (NASDAQ:RLYP) gained $1.25, to close at $23.24 after the company reported positive findings from an onset-of-action study of patiromer.