West Coast Editor

Ceregene Inc. is keeping U.S. and Canadian rights to its Phase II drug for Parkinson's disease and getting $25 million up front plus as much as $125 million in milestone payments, along with 50 percent of worldwide Phase III costs covered, through a deal with Genzyme Corp, which will pay royalties on sales in other territories.

Genzyme "appreciates the ups and downs of gene therapy," said Jeffrey Ostrove, president and CEO of San Diego-based Ceregene. Those have been "mostly down, no question about it," he added - but Ceregene might have found something that works.

"We deliver extremely small volumes of our product, as measured in microliter amounts, to very targeted regions, in a protected space," Ostrove said. Others have infused larger volumes into the bloodstream or tumors, prompting unfavorable immune responses to the vectors and, in some cases, the products themselves.

Not so - at least so far - with Ceregene's lead compound CERE-120, made up of an adeno-associated virus (AAV) vector carrying the gene for neurturin (NTN), a member of the same protein family as glial cell-derived neurotrophic factor, patents for which are owned by Amgen Inc., of Thousand Oaks, Calif.

"We don't believe we're growing new nerves," Ostrove said. "We're rescuing existing nerves from death." CERE-120 fits well with Cambridge, Mass.-based Genzyme gene-therapy portfolio, including a Phase I/II therapy for Parkinson's disease, gained in the buyout of AAV technology from Avigen Inc., of Alameda, Calif. (See BioWorld Today, Dec. 22, 2005.)

That candidate is designed to restore therapeutic oomph of levodopa by boosting the brain's ability to convert it into dopamine. Unlike CERE-120, used in mid-stage patients, the Avigen compound is for late-stage disease. "At this point we don't know enough about it" to determine whether the Avigen drug might be used in some form along with CERE-120, Ostrove said.

In April, at the meeting of the American Association of Neurological Surgeons, Ceregene presented 12-month follow-up data from an open-label Phase I trial, showing the drug well tolerated, with patients demonstrating a 36 percent (p<0.001) reduction in Parkinson's symptoms at 12 months after getting CERE-120. "It would have to be a pretty big placebo affect, if that's what it was, but you never know," Ostrove noted.

The study was partially funded by The Michael J. Fox Foundation for Parkinson's Research, which has also chipped in $1.9 million to support Phase II work. In April, Ceregene started enrolling the Phase II trial, aiming for 51 patients with advanced Parkinson's. Two-thirds will get CERE-120 via stereotactic neurosurgery and one-third placebo. Patients will be followed for 12 months for safety and efficacy results. Ostrove expects to unblind the trial in the fall of next year, and "get a very good indication of whether this works in man," Ostrove said.

Nothing is approved for Parkinson's. Unlike previous methods of similar therapy that have been tried - which involved infusion into ventricles or a canula in the striatum - Ceregene's delivery is designed to mimic natural expression in the striatum. (See BioWorld Today, March 12, 2007.)

"Ceregene didn't set out to be a gene therapy company," Ostrove said. "The idea was to deliver growth factors in a safe and effective means, but you can't just inject them intravenously. We settled on gene delivery as the only way to get the protein where it needed to be."

Ceregene, with 41 employees, stands in good shape financially, Ostrove said. The firm closed a Series C round in January, selling $21.8 million in shares, and has spent frugally. A previous round raising $32 million closed in August 2004, and "we still had some of that money left" at the start of this year, Ostrove said.

News-making events ahead for the firm include the kick-off of Phase II trials early next with CERE-110 for Alzheimer's disease. In early May, at the American Academy of Neurology meeting, Ceregene offered positive interim Phase I data with the gene therapy. "We may be dosing some additional patients" in that trial, Ostrove said.

Genzyme's stock (NASDAQ:GENZ) closed Thursday at $64.69, up 28 cents.

Gene therapy in systemic disease is "a little difficult," said Stephen Dunn, analyst with Dawson James, dryly understating the case. Dunn covers Introgen Therapeutics Inc., of Austin, Texas, which at this year's meeting of the American Society of Clinical Oncology reported encouraging Phase II data in head and neck cancer with Advexin, which combines the p53 tumor suppressor gene with a non-replicating, non-integrating adenoviral gene-delivery system.

"They're the Microsoft of gene-therapy companies," Dunn said of Introgen. Enthusiasm for the firm on Wall Street generally is not great, but "they're going to have the first gene-therapy filing in the Western world this year," he said. Seattle-based Targeted Genetics Corp. has done less well, he added. The company discontinued development of its lead cystic fibrosis drug in March 2005 after a disappointing Phase IIb study.

Others pursuing aspects of Parkinson's include San Diego-based Acadia Pharmaceuticals Inc., which just over a week ago started the first of two pivotal Phase III trials planned for pimavanserin in Parkinson's psychosis, which afflicts up to 40 percent of the 1.5 million Americans with the ailment and often is what puts them in nursing homes. Doctors typically try backing off the dopamine agonist therapy used to control tremors, but this can result in a loss of motor control. Atypical antipsychotics are prescribed off-label. (See BioWorld Today, June 12, 2007.)

Earlier in the month, Faust Pharmaceuticals SA, of Strasbourg, France, said at the Movement Disorder Society meeting that Phase IIa trial results of its small-molecule glutamate release inhibitor, FP0011, demonstrated tolerability, as well as improved Parkinsonian symptoms and motor fluctuations. Eight mid- to late-stage Parkinson's disease patients with L-dopa-induced motor complications took part.