BioWorld International Correspondent

If at first you don't succeed, try, try again.

GlaxoSmithKline plc has taken that old adage to heart. Undeterred by the previous failure in Phase II trials of a candidate antidepressant it had licensed from the Danish firm NeuroSearch A/S, it has returned to the well in search of a fresh source of triple-action compounds that block reuptake of the neurotransmitters dopamine, noradrenaline and serotonin.

The companies entered a new collaboration focused on the discovery and development of mixed monoamine reuptake inhibitors for treatment of depression and other mood disorders. Ballerup-based NeuroSearch could receive up to US$27 million in milestone payments, plus product royalties, on the first compound derived from the program that reaches the market. It would receive additional milestones and potential royalties on subsequent molecules that enter clinical development.

The agreement effectively replaces an earlier accord between the companies, which hit a bump when they decided to withdraw the Phase II-stage candidate antidepressant NS2389 from clinical development this year, following the observation of unexplained hyperplasias in animal species in receipt of high doses of the compound. They originally planned to focus on backup candidates, said Finn S rensen, NeuroSearch's director of licensing and business development, but they subsequently decided to screen several new chemical series instead.

London-based GlaxoSmithKline paid US$10 million up front to gain access to the NS2389 development program, at which point it had already reached Phase II clinical trials. The total value of that agreement was US$57 million, plus royalties. The new deal is structured differently, to take into account the fact that it is at a different stage of maturity. "In this deal there is no signing fee," S rensen said. "It's early stage."

The endgame is unchanged, however. The companies believe they can find a drug that will have a faster onset of activity and a wider population of responders compared to depression drugs that are on the market. "We need to prove that in clinical studies," S rensen said.

The discovery and development of triple-action monoamine reuptake inhibitors is a core activity at NeuroSearch. Those compounds have potential application in a broad range of neurological disorders. One, NS2330, is at the Phase II stage for treatment of Alzheimer's and Parkinson's diseases. It was the subject of an agreement worth up to US$80 million with Boehringer Ingelheim, of Ingelheim, Germany.

"It is, of course, not that easy to partner at an early stage when you do not have specific compounds," S rensen said. In the company's favor, he said, was its good cash position and its strength in medicinal chemistry. "It is easier for us since we're talking products," he said.

Investors responded positively to the news Monday, pushing up NeuroSearch's share price by 9.3 percent to DKK53. It ended the day as the third biggest gainer on the Copenhagen Stock Exchange.