LONDON – Genkyotex SA has raised CHF25 million (US$26 million) as an extension to its Series C, with the existing investors all following on to fund Phase II development of the lead compound, GKT137831 in diabetic nephropathy.

That follows the initial results of the Phase I trial of the first-in-class NOX inhibitor, published last month, which returned positive findings on safety, tolerability and pharmacokinetics.

The Phase I development has now progressed to a Phase Ib multi-ascending dose study in which volunteers will be dosed for 10 days.

"We now know we've got something we can dose once or twice a day," Ursula Ney, CEO, told BioWorld Today. "We knew we would have to raise money for the Phase II development, and the investors in the Series C all wanted to invest again in this [follow-on], which we did as an extension to the Series C, because it was simpler."

With the cash on hand, it is expected to complete Phase Ib and start the Phase II program before the end of 2012.

The funding was led by Edmond de Rothschild Investment Partners, with the Swiss bioincubator Eclosion, Vesalius Biocapital and MP Healthcare Venture Management. In the first tranche of the Series C in May 2011, Geneva-based Genkyotex raised $20.4 million.

Gilles Nobecourt, Partner at Edmond de Rothschild, said Phase I demonstrated Genkyotex is in the lead in translating NOX inhibition – nicotinamide adenine dinucleotide phosphate oxidases to give the enzymes their full name – to the clinic, laying the ground for an entirely new class of therapy.

"We believe targeting NOX is very promising, with many potential therapeutic indications," Nobecourt said.

GKT137831 is an inhibitor of NOX-1 and NOX-4, enzymes that are responsible for generating reactive oxygen species (ROS) that modify biological pathways and cause tissue damage that is the hallmark of a number of metabolic, cardiovascular, pulmonary and neurodegenerative diseases.

Attempts have been made to develop scavenger drugs to mop up ROS after they are generated, but Ney contended that by preventing the production of ROS in the first place, NOX inhibition will have a greater effect.

The complete NOX enzyme family consists of five isoforms and two analogues. As Genkyotex's technology allows it to selectively screen for different inhibitors, there is much riding on the progress of GKT137831 in terms of validating the platform as a whole.

The Phase II placebo-controlled randomized study will recruit three dose groups with 30 to 50 patients in each group who will be treated for three months, with the primary endpoint of a reduction in proteinuria. Ney noted this is a "very accepted" clinical measure of impaired filtration by the kidneys and an easy endpoint to assess. In addition, the company has preclinical data from a mouse model indicating that albumin in urine is a clear indicator that GKT137831 is having a clinical effect.

Results of the Phase II are expected in early 2014, and the new funding will last until well into 2014.

"This gives us time to get to the end of Phase II, providing proof of concept for the molecule and the platform, and look for partners," Ney said.

Ney was prospecting for potential partners at the BIO Convention in Boston last month and said there is a lot of interest. That arises from two directions. First – pharma companies are paying attention to the fast rate at which basic research in oxidative stress is now getting translated through to the clinic, and are keen on targeted approaches for preventing it. Second – the whole field of fibrosis is attracting interest.

"Companies are looking for new opportunities in this field. Nephropathy is a fibrotic disease, and it's been shown the NOX-4 enzyme is implicated in other forms of fibrosis," Ney said. That includes liver and lung fibrosis.

NOX-1, on the other hand, is involved in angiogenesis, atherosclerosis and other diabetic co-morbidities, and has shown an effect in disease models of those pathologies.

Overall understanding of NOX enzymes, the different roles of the various isoforms, and the part the enzymes play in disease, is advancing rapidly. Alongside progressing clinical development of GKT137831, Genkyotex will continue to screen for, and advance, a backup compound and to identify other inhibitors. The company is involved in one publicly funded research program that is looking for NOX-1 and NOX-2 inhibitors, with neurodegenerative diseases as the target application.

"We've really been expanding high-throughput screening and the chemistry base of the company. It's still early days with other molecules, but we are beginning to see other patents coming through," Ney said.

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