Third time lucky for Parkinson's drugs?

Only six weeks ago, Brane Discovery was spun out of Nikem Research, itself a 2001 spin off from GlaxoSmithKline (GSK). The Italian-based speciality pharma company will focus on central nervous system (CNS) drugs, and, as such, has now bought a preclinical programme off Nikem that targets the Opioid Receptor Like-1 (ORL-1) - a G-protein-coupled receptor (GPCR). This programme actually originates from GSK, which out-licensed the programme to Nikem in January 2004. So, ORL-1 finds itself in the hands of a third company in as many years, but one person who has followed the programme all the way is Brane's new CEO, Dr Carlo Farina, who also used to be the CEO at Nikem. He explained to DrugResearcher.com that he has been researching ORL-1 since the late 90s and that the reasons the programme had changed hands were very simple. When, in 2000, GSK was formed from the merger of Glaxo Wellcome and SmithKline Beecham, the pharma giant decided to close its facility in Milan and relocate to Verona. At that time, some of the people in Milan took the opportunity to propose a spin off and soon Nikem was born. Farina went on to say that the original idea of the company was to provide medicinal chemistry services to the pharma industry and the money was used to fund internal R&D. However, these services were the company's only source of income - there were no investors - and as the internal programmes advanced towards the clinic, the costs grew and it was decided to separate the two arms of the business through a second spin out. "Nikem Research's collaboration on ORL-1 with GSK has been extremely productive in the past years, and we sincerely thank GSK for the recognition of Nikem's success in identifying a preclinical candidate,"​ continued Farina. "The spin-off of all IP from NiKem to Brane, and the creation of a highly competent clinical development team, led by Ruggero Farriello at Brane, makes us the ideal developer for this lead candidate, and will ensure success in taking the project timely and effectively to clinical proof of concept." ​​A pipeline of NCEs ​ The ORL-1 research has already produced one preclinical drug candidate, dubbed BND-001, which has a novel mechanism of action. By interacting with ORL-1, it causes inhibition of adenylate cyclase and of the voltage sensitive Ca2+ channels, and increases the outward K+ conductance. The receptor is found across the CNS, but particularly in the forebrain, brainstem, and in both dorsal and ventral horns of the spinal cord. It is also expressed in the periphery in smooth muscles, peripheral ganglia and the immune system. Drugs for this target could also, therefore, potentially treat depression, neuropathic pain, learning and memory, as well as Parkinson's Disease. BND-001 is a New Chemical Entity (NCE) - also called a New Molecular Entity (NME), which is defined as a molecule that contains no active part that has been previously approved by the US Food and Drug Administration (FDA). These innovative drug candidates are much rarer than the 'me-too' drugs that make up the majority of chemicals tested by the FDA. Out of 40 new drugs approved by the FDA so far this year, only seven have been classed as NCEs, and one of those had already been approved in Europe over a year ago. Farina said that BND-001 is scheduled to begin Phase I clinical trials by the third quarter of 2008, as the company still has to complete preclinical tests of the drugs efficacy in primates before moving into humans. Brane also has several 'backup' drug candidates in the BND-001 programme, leading to two NCE patents, explained Farina. In the company's others research programmes, there are 6 NCE patents and 3 patents associated with using existing drugs in new therapeutic indications, leaving it owning 12 patents overall. Farina believes that BND-001 could be worth hundreds of millions of dollars per year and could even become a blockbuster drug - especially since it could treat some symptoms of Parkinson's not addressed by current therapies and so become a first-line treatment in combination with other drugs. Its most advanced programme is BND-003, a pyrrolidinone derivative that is concerned with the treatment of neuropathic pain. A much bigger market than Parkinson's, Farina is confident a successful drug would be a blockbuster - an assertion matched by Brane's chief scientific officer, Dr Ruggero Fariello. Fariello continued: "Brane's two lead products [001 and 003] have substantial and robust IP protection and established preclinical proof-of-concept." ​ Farina believes that BND-003 will be ready to enter the clinic in the fourth quarter of this year for the orphan indication of anti-viral induced neuropathic pain. If successful, the drug would then go on to two Phase II trials, one in the same indication and one for osteoarthritis induced pain. A second lead compound, to treat chemotherapy induced pain, could enter Phase I trials in the middle of 2008, he said. However, before this happens, Brane is currently addressing issues regarding the compound's pharmacokinetic profile. While many companies, such as Roche, Schering and Johnson & Johnson, have conducted research into ORL-1 activator drugs in the past, fewer companies have looked at blocking the receptor. Of those that have, there are no drugs currently in clinical testing. The German pharmaceutical company Grünenthal is one company looking at ORL-1 inhibitors, as are Japan Tobacco and Merck & Co's Japan subsidiary, Banyu Pharmaceuticals. The third major part of Brane's pipeline contains oncology drug candidates, specifically v-ATPase inhibitors (BND-002). Brane is currently seeking licensing or co-development partners. As well as these three more advanced programmes, Brane has a fully operational discovery programme with a number of CNS Exploratory Projects undergoing early validation. The sale of the ORL-1 programme to Brane has allowed Nikem to rid itself of the last of its internal research programmes and concentrate its efforts solely on providing drug discovery services. These proprietary programmes were formerly perceived as a potential "conflict of interest" issue by some of NiKem's clients "Our decision to spin-off our R&D pipeline into Brane maximises our chances to become an even more successful Drug Discovery service company, and ensures a proper environment for the CNS-related IP and projects in Brane. The transfer of NiK-001, now BND-001, into Brane is a logical consequence of our strategic decision,"​ said Giuseppe Giardina, CEO of Nikem.