Thrasos Therapeutics Inc.'s $21 million series D financing will let the firm push further into chronic kidney disease (CKD) with a separate compound while pursuing acute kidney injury (AKI) in patients undergoing major surgery with lead compound THR-184.

"We've got some work to do," Richard Andrews, CEO of the Montreal-based firm, told BioWorld Today. Staging of development for the second candidate – TH-575 for diabetic nephropathy, a leading cause of CKD – is still being determined, and two more prospects are positioned behind it, also in the renal space, he said. Meanwhile, THR-184, given fast track status by the FDA, is the subject of a 450-patient phase II trial for patients at risk of AKI who are undergoing cardiac surgery at 40 sites in Canada and the U.S.

The AKI experiment "was originally conceived as an adaptive study," Andrews said. "We started with three doses as well as a control, and we took that to an interim analysis last August. Now we're continuing with two doses," and the company should have data in the first half of next year. AKI, which causes a sudden loss of kidney function, afflicts more than 1.2 million people each year in the U.S. BDC Capital and SR One led the series D round, with participation by all current investors. Ela Borenstein, managing partner at BDC, is joining Thrasos' board.

THR-184 was invented by scientists at the company, founders of which were "able to generate a series of peptides that showed activity" in the bone morphogenetic (BMP) pathway, Andrews said. More specifically, the lead compound works in the BMP/small mothers against decapentaplegic (Smad) pathway, Smads being the signaling molecules involved.

BMP is "well known and well documented to affect first of all the generation and development of the kidneys," Andrews said. "It's also been shown in many studies that the protein can protect the kidney from insult, whether it's acute or chronic. The protein is very hard to use and very expensive, and can only be delivered intravenously. It also promotes bone growth. Our peptides have no bone growth [effect], act on the pathway and preserve all those beneficial effects – cell protection, cell development and organ protection." About one in 10 American adults has kidney disease, most of them with diabetes or hypertension.

Cardiac surgery "of course is a fairly significant intervention" and can, like any major surgery, lead to AKI, "either [in the form of] a reperfusion injury or the result of a significant amount of inflammation that comes from the surgical procedure," Andrews said. No preventive or therapy is available for AKI now. "There's a small degree of mortality [with the condition], and certain patients have renal failure and need dialysis," he said. "Frankly, some may remain on dialysis. That incidence rate is fairly low. The real severe problem is much extended time in the hospital, a lot more care that goes into them. Their rate of progression toward kidney failure is increased."

Cortellis Clinical Trial Intelligence lists 209 studies in renal injury, 16 having reached the phase III stage, of which seven are still recruiting. For Thrasos, partnership discussions likely will happen down the road. "We know that pharma is very interested in this space, and that the commercial opportunity is huge," Andrews said. "There are over 3 million major surgeries [in the U.S.] every year, and there's a fairly significant event rate for AKI. We've had a lot of interest from [pharma firms], and so I expect we're going to be talking to them over time. The phase at which we partner really depends on the partner, what they bring to the table and how we work together." In October 2012, Thrasos raised $35 million, intended to get through the phase II experiments with THR-184. (See BioWorld Today, Oct. 26. 2012.)

Abbott Park, Ill.-based Abbott in mid-2012 paid $110 million in cash to acquire from privately held Aarhus, Denmark-based Action Pharma A/S a first-in-class alpha-MSH peptide derivative, AP214, designed to prevent AKI during major cardiac surgery in patients at increased risk. The pharma giant has completed a phase II trial with fenoldopam and N-acetylcysteine in cardiac surgery AKI, both drugs having previously been shown to protect kidney function in circumstances that cause kidney stress. (See BioWorld Today, May 9, 2012.)

Also busy in the AKI space is AM-Pharma BV, of Bunnik, the Netherlands, which has recombinant alkaline phosphatase (recAP) in an adaptive phase IIa/IIb test to investigate the effect of recAP in patients with sepsis-associated AKI in 50 sites in the U.S. and in Europe, recruiting 290 patients altogether. The first four-arm stage, with 120 patients, will identify the most effective of three different doses of recAP. In the second stage, 170 additional patients will be recruited in two arms of 85 each to receive either the best dose of recAP as identified in stage one or placebo. (See BioWorld Today, Sept. 23, 2013.)

Thrasos takes its name from the classical Greek word meaning "boldness." Aficionados of James Bond movies may recall the dialogue from 1981's "For Your Eyes Only," in which one of the characters tells Bond he has "what the Greeks call 'thrasos' – guts." Series D co-leader SR One is the independent corporate venture capital arm of London-based Glaxosmithkline plc, and has a portfolio of more than 35 public and private firms. BDC Capital is a subsidiary of the Business Development Bank of Canada, and has more than $1 billion under management.