BioWorld International Correspondent

Apeiron Biologics AG licensed its lead program APN01, a recombinant form of human angiotensin converting enzyme 2 (ACE2), to London-based GlaxoSmithKline plc in a deal valued at up to €236 million (US$329.4 million).

That figure includes an initial payment of €13.5 million, which consists of an up-front payment and an equity investment in the Vienna, Austria-based firm, as well as milestone payments. The company also would receive double-digit royalties on eventual product sales.

Apeiron completed the deal without any venture capital investment, having raised almost €7 million from founders, friends and angel investors.

"That's very unusual," CEO Hans Loibner told BioWorld International. "It's never happened in Austria, that's for sure. I'm not sure how often it's happened in Europe."

Then again, Apeiron is not a run-of-the mill start-up. Its founder Josef Penninger is probably the country's best-known biomedical scientist.

He was a high-profile young researcher at the Amgen Research Institute in Toronto from 1994 to 2002, before returning to Vienna to lead the newly created Institute of Molecular Biotechnology (IMBA), a joint initiative between the Austrian Academy of Sciences and Boehringer Ingelheim GmbH, of Ingelheim, Germany.

Penninger has made important discoveries in several areas, including pinpointing the role of Rank Ligand (RANKL) in bone resorption. Apeiron is developing three programs based on his work. APN01, the most advanced, is based on his finding that ACE2 has a role in preventing lung injury.

The enzyme reduces levels of angiotensin II, the main effector molecule in the renin angiotensin system, which plays a central role in controlling blood pressure and electrolyte balance. Underexpression of ACE2 is associated with a pathological phenotype in a range of conditions, Loibner said.

Administering the protein offers an alternative route to modulating the pathway currently targeted by inhibitors of ACE, the enzyme responsible for angiotensin II production.

The company has developed a GMP production process for the 110 KDa protein, which is biologically active as a homodimer.

It also has amassed promising preclinical data on APN01 in a range of disease models, including acute respiratory distress syndrome (ARDS), diabetic nephropathy, live fibrosis and hypertension.

In ARDS, for example, it has shown that the protein leads to an improvement in lung function and an increase in blood oxygenation, Loibner said. Preclinical data also indicated that the protein does not cause a drop in blood pressure, which had been a theoretical concern. "You bring down elevated blood pressure to normal, but you never go below normal," he said.

The company has already completed a dose-escalation Phase I trial in healthy volunteers in Switzerland. No side effects were observed, Loibner added.

The GSK deal, which covers all potential indications for APN01, offers significant validation for Apeiron.

Its other programs are at an earlier stage of development. That includes a program for a pain target called downstream regulatory element antagonistic modulator, which inhibits synthesis of the endogenous opioid dynorphin.

Published  February 10, 2010