West Coast Editor

SAN FRANCISCO - Early arrivals for Tuesday night registration at the Biotechnology Industry Organization's InvestorForum conference got a rainy taste of the Bay Area's autumn turning to winter, but by noon of the first full day of the meeting, skies had cleared.

Seattle-based Cell Therapeutics Inc., which presented to attendees Wednesday, is making plans for a similarly sunny turnaround with Zevalin (ibritumomab tiuxetan), the non-Hodgkin's lymphoma therapy CTI is buying from Biogen Idec Inc. for $10 million plus as much as $20 million in milestone payments and royalties. (See BioWorld Today, Aug. 17, 2007.)

Zevalin, consisting of a monoclonal antibody linked with the radioisotope Yttrium-90 to target the CD20 antigen on mature B cells and B-cell tumors, won FDA clearance in 2002 for relapsed or refractory low-grade, follicular or transformed B-cell non-Hodgkin's lymphoma, including those with disease not responding to therapy with Rituxan (rituximab, also from Biogen Idec).

The drug ran into adoption problems right away, and it soon became clear that the compound's once-anticipated blockbuster status would not soon pan out. "There are logistic issues that need to be addressed in how clinics can apply Zevalin," as James Bianco, president and CEO of CTI, told BioWorld Today before speaking at the conference. Clinics need to establish community access programs, "getting sites set up so they have radioactive material licenses," he said.

Physicians didn't want to send patients to hospitals for treatment, and treated them with chemotherapy and Rituxan instead. Co-promoted in the U.S. with South San Francisco-based Genentech Inc, Rituxan sold $4 billion last year. CTI aims to expand the label for Zevalin, moving it into a front-line setting, Bianco told conference attendees.

The drug can be used in equipped clinics since it doesn't require any special shielding and is provided as a "shake and shoot [therapy], ready to load for administration." And Zevalin could work after a one-time infusion - compared to a half-dozen chemo regimens followed by Rituxan.

"We think it's the right time now for radiopharmaceuticals," Bianco said. The Zevalin deal with Biogen Idec is expected to close at the end of this month, and Bianco has said he expects peak sales of the compound - which brought in only $18 million worldwide last year for Biogen Idec - to reach $250 million.

Another conference presenter that might be due for more good news shortly: Acadia Pharmaceuticals Inc., of San Diego, expected by analysts to garner a big pharma deal by the end of the year for pimavanserin in schizophrenia, while keeping other North American rights. Known also as ACP-103, the compound targets the 5-HT2A receptor, and acts an inverse agonist rather than an antagonist.

Thomas Aasen, chief financial officer of Acadia, said the compound has "ideal drug-like properties" for once-per-day oral dosing. Though schizophrenia hits up to 3 million people in the U.S. and about 1 percent of the world's population, he said, existing drugs "leave a lot to be desired. They're not effective in all the patients [and] they don't treat all the symptoms of the disease."

Available therapies help with such problems as hallucinations and delusions, Aasen said, but do little for social withdrawal and cognitive deficits, while bringing severe side effects that result in "extremely poor compliance" by patients.

Mark Monane, analyst with Needham & Co., looked forward in a research report last month to Acadia's full Phase IIb data, due for disclosure at a medical conference, and said the drug's Phase II success in two indications "significantly de-risks the program," boosting the chances of a partnership before 2007 finishes. Acadia started a Phase III trial with pimavanserin in Parkinson's disease psychosis this summer. (See BioWorld Today, June 12, 2007.)

"With encouraging proof-of-concept data in hand and a strengthened balance sheet, we believe Acadia is in a strong negotiating position with big pharma," Monane wrote, repeating his "buy" rating and $17 price target. Ajim Tamboli, analyst with Lehman Brothers, sounded even more optimistic, tagging Acadia with an "overweight" rating and upping the target price from $18 to $28.

Acadia also has ACP-104, an active metabolite of clozapine (N-desmethylclozapine), an atypical antipsychotic approved in the U.S. in 1990 for schizophrenia. Clozapine works, but a few patients - as much as 1 percent of the treated population - develop agranulocytosis, which can be fatal, so their blood must be tested regularly. About 8 percent of clozapine patients end up with neutropenia.

ACP-104, is a partial agonist against D2 and D3 receptors, while most antipsychotics are full agonists. ACP-104 is an M1 agonist as well, while clozapine is an M1 antagonist and a D2 antagonist.

Acadia kicked off a 42-day, three-armed Phase IIb proof-of-concept trial in schizophrenia in June 2007, enrolling 240 patients, with data possibly available in the second half of this year.

Antipsychotic drugs sell more than $15 billion worldwide, Aasen said, and all of the market leaders bear a "relatively limited patent life," most losing protection before or during 2011.

The firm has a Phase II neuropathic pain drug and preclinical ophthalmologic drug partnered with Allergan Inc., of Irvine, Calif., as well as a muscarinic receptor discovery deal with Sepracor Inc., of Marlborough, Mass.

The BIO InvestorForum, expecting about 1,150 attendees, continues through today at the Palace Hotel.