BioWorld International Correspondent

Noxxon Pharma AG added €37 million (US$50.3 million) to its coffers in a Series C round that will enable the company to take its two lead programs, NOX-E36 and NOX-A12, into development for lupus nephritis and diabetic retinopathy, respectively, through clinical proof of concept.

Noxxon's preclinical pipeline is based on its proprietary Spiegelmer platform, originally developed at the Free University of Berlin by company co-founder Sven Klussmann, who is now both CEO and chief scientific officer at the Berlin-based firm.

The name derives from "spiegel," the German word for mirror. A Spiegelmer is a synthetic aptamer - or protein-binding oligonucleotide - whose individual nucleotide residues contain L-sugar moieties instead of the D-sugars found in naturally occurring nucleotides.

The new funding round pushes Noxxon's total funding to €80 million since its formation in 1997. "I believe platform technologies are back in the game, and this certainly helped us," Klussmann said.

Recent acquisitions, such as those of San Francisco-based Sirna Therapeutics Inc. and Cambridge, UK-based Domantis Ltd. by Merck & Co. Inc., of Whitehouse Station, N.J., and London-based GlaxoSmithKline plc, respectively, underline the revival. "These were quite significant platform M&A deals," he said.

Noxxon's most advanced Spiegelmers target extracellular proteins that also are targeted by monoclonal antibodies, but the company also has demonstrated in vivo efficacy of Spiegelmers directed against intracellular targets, such as transcription factors.

"We need a good delivery system to make it work," Klussmann said. At present, Spiegelmers are delivered systemically via injection, although in time, the company would like to explore the potential for nasal or pulmonary delivery.

The company claims that unlike conventional aptamers, Spiegelmers offer high levels of stability, while avoiding the problems with aggregation and immunogenicity that can hamper the efficacy of monoclonal antibodies and other protein-based drugs. It was unable to raise antibodies against several Spiegelmers, Klussmann told BioWorld International, and assays against Toll-like receptors, which can be activated by foreign DNA or RNA, "were totally silent."

NOX-E36, which is slated to enter the clinic in late 2008, binds the pro-inflammatory chemokine monocyte chemotactic protein-1 (MCP1), which is involved in the recruitment of monocytes to sites of inflammation. It has potential application in a range of autoimmune conditions, including multiple sclerosis and rheumatoid arthritis, Klussmann said.

Lupus nephritis was attractive because the condition is well understood, although poorly served by existing therapies. "There's a lot of data around kidney inflammation and the target," he said.

The condition affects about half the systemic lupus erythematosus patient population, which in the U.S. numbers 900,000 people.

Next up is NOX-A12, which targets a chemokine involved in promoting angiogenesis. That compound is due to enter the clinic in early 2009. In parallel with those two lead programs, Pfizer Inc. is developing an anti-ghrelin Spiegelmer, NOX-B11, as an anti-obesity therapy, following a deal struck between the two firms last year. New York-based Pfizer also took an equity position in Noxxon at the same time and has an ongoing research relationship with it as well. "It was quite an important deal for us - a validation deal if you like," Klussmann said.

Munich-based TVM Capital GmbH and Soffinova Partners, of Paris, co-led the new round. Edmond de Rothschild Investment Partners, also of Paris, was another major participant in the investment syndicate.

Jena, Germany-based Deutsche Effectenund Wechsel-Beteiligungsgesellschaft (DEWB) AG also participated, although its previous majority stake has been reduced to approximately 28 percent. It remains Noxxon's largest shareholder, however.

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