Ardea Biosciences Inc. (formerly IntraBiotics Pharmaceuticals Inc.) is back from the brink, sporting a new name, a new management team and a new suite of preclinical programs in HIV, cancer and inflammatory disease.
Some may remember the troubled history of IntraBiotics: Back in 2002, lead drug iseganan failed a Phase III trial in oral mucositis, causing the company's stock to drop 70 percent. Then in 2004, the company discontinued a trial of the drug in ventilator-associated pneumonia due to safety issues, sending the stock down another 69 percent. In 2005, the company terminated all regular employees and discontinued operations. (See BioWorld Today, Oct. 1, 2002 and June 24, 2004).
Late last week, an almost unrecognizable Ardea Biosciences rose from the ashes of IntraBiotics and announced its acquisition of preclinical programs in HIV, cancer and inflammatory disease from Valeant Pharmaceuticals International Inc.
Under the terms of the deal, Ardea will assume development of the programs and will pay Valeant clinical milestones as well as royalties on future sales. Milestone payments could total $67 million if a product from all three programs is commercialized, but there are no milestones tied to subsequent products developed in the programs. In each program, the first milestone will be due after the completion of a proof-of-concept clinical trial, and more than half of the milestone payments will follow regulatory approval. Royalties will be in the mid-single digits.
In exchange for paying the milestones and royalties, Ardea gets the intellectual property, preclinical data, product inventory, research equipment and development and commercialization rights for all three programs. It intends to market the resulting products in the U.S., the UK, France, Spain, Italy and Germany.
Aliso Viejo, Calif.-based Valeant retains the option to evaluate the first HIV candidate to complete Phase IIb trials and may reacquire commercialization rights outside of the U.S. and Canada. If Valeant exercises that option, Ardea will complete Phase III trials and regulatory filings before handing the product back, and will then receive a $10 million option fee, up to $21 million in milestone payments and a mid-single digit royalty.
The most advanced of the three programs is the 800 Series, which is in late preclinical development. Lead candidate AR806 is a non-nucleoside reverse transcriptase inhibitor (NNRTI) for HIV treatment and has been shown in in vitro testing to inhibit a wide range of HIV viral isolates, including isolates that are resistant to efavirenz (Sustiva, Bristol-Myers Squibb) and other marketed NNRTIs. Early preclinical data also indicate that AR806 could be formulated as a once-daily pill and may have limited pharmacokinetic interactions with other drugs. Ardea plans to begin clinical trials in the second quarter of 2007.
Just behind AR806 is the 100 Series, led by AR119, a small-molecule inhibitor of MEK (Mitogen-activated ERK Kinase) for cancer and inflammation. Also in preclinical development is the 900 Series, a class of NNRTIs that Ardea believes may be able to improve on the 800 Series, offering greater activity against a wide range of drug-resistant viral isolates. Ardea hopes to move AR119 into the clinic in the third quarter of 2007 and follow it up with a clinical trial for the lead compound in the 900 Series in the fourth quarter.
While the three programs now serve as the foundation of Ardea's pipeline, off-loading them was an important step in Valeant's restructuring initiative. After two Phase III failures with hepatitis C drug Viramidine earlier this year, Valeant announced a plan to trim expenses and focus on late stage programs, including a Phase IIb trial of higher doses of Viramidine and a Phase III trial of retigabine for epilepsy. As part of its restructuring, Valeant out-licensed hepatitis B drug pradefovir to Schering-Plough Corp., of Kenilworth, N.J., earlier this month. (See BioWorld Today, March 22, 2006, and Dec. 15, 2006.)
In a separate agreement, Valeant signed a one-year extendable deal in which Ardea will advance a preclinical program in neuropharmacology in exchange for $3.5 million in fees annually and up to $1 million in milestones. For Ardea, the extra cash will supplement the $48.3 million the company expects to have on hand as of Dec. 31, 2006, providing it with funding into 2008.
In addition to the changes in its name and pipeline, Ardea announced that it hired Barry Quart as president and CEO. Quart previously served as president of Napo Pharmaceuticals Inc., of South San Francisco, and in senior positions at New York-based Pfizer Inc. Ardea also added Zhi Hong, formerly of Valeant, as executive vice president of research and chief scientific officer, and Kimberly Manhard as senior vice president of regulatory affairs and operations. Denis Hickey resigned as CEO but will remain chief financial officer. The company is also hiring approximately 50 additional employees.
Ardea is leaving Palo Alto, Calif., relocating its corporate headquarters to San Diego and its research facilities to Costa Mesa, Calif. The company expects to shed its pink sheet listing for a Nasdaq ticker "in the near future," according to its press release.
Neither company returned calls seeking comment.