XenoPort Announces Initiation of Clinical Trials

XenoPort, Inc. (Nasdaq:XNPT) announced today that it has initiated separate Phase 2 clinical trials of XP19986 in patients with gastroesophageal reflux disease, or GERD, and in spinal cord injury patients with spasticity. In addition, XenoPort announced the initiation of the first clinical trial of XP21279, a drug candidate designed to treat Parkinson’s disease. Ronald W. Barrett, Ph.D., chief executive officer of XenoPort, stated, "We are pleased to report these advancements in our XP19986 and XP21279 clinical development programs. Given our earlier positive results with single doses of XP19986 in GERD patients, we believe this new GERD clinical trial will enable us to identify effective doses of XP19986 when administered for one month. We will also be able to examine XP19986’s potential for once-a-day treatment of GERD patients. The spasticity clinical trial will offer a first look at the potential of XP19986 to treat patients with spasticity associated with spinal cord injury. The XP21279 clinical trial in healthy subjects is designed to help us to understand if our Transported Prodrug of L-Dopa will enable a more optimal pharmacokinetic profile with the potential to avoid side effects and periods of ineffectiveness that are associated with current L-Dopa therapy.” XenoPort also confirmed plans to release top-line data from two Phase 3 clinical trials of XP13512 in patients with restless legs syndrome, or RLS, in the first quarter of this year. XenoPort also stated that GlaxoSmithKline, or GSK, its partner for XP13512 in the U.S. and other countries worldwide, excluding certain Asian countries, plans to file a new drug application for XP13512 for RLS with the U.S. Food and Drug Administration in the third quarter of 2008. GSK has stated that it also intends to initiate two polysomnography studies of XP13512 in RLS patients in the second half of 2008 to explore XP13512’s potential benefits in sleep. XenoPort also reiterated GSK’s plans to initiate additional clinical trials of XP13512 in other central nervous system related disorders. GSK has announced that it intends to initiate separate dose-ranging, Phase 2 clinical trials of XP13512 in post-herpetic neuralgia, or PHN, and painful diabetic neuropathy, as well as a Phase 2 clinical trial in PHN patients who have not responded to treatment with gabapentin, all in the first quarter of 2008. In addition, GSK has announced that it expects to initiate, after discussion with the FDA, two pivotal dose-ranging efficacy studies and an open-label, long-term study of XP13512 for migraine prophylaxis in the second half of this year. XP19986 Phase 2 Clinical Trial in Patients with GERD XenoPort’s randomized, parallel-group, double-blind, placebo-controlled Phase 2 clinical trial of XP19986 is designed to evaluate the efficacy, safety and tolerability of a sustained-release formulation of XP19986 (designated as SR3) in patients with symptomatic GERD. The clinical trial is being conducted in approximately 150 patients at multiple study centers in the United States. Eligible subjects must be diagnosed by a gastroenterologist as suffering from GERD and have symptoms (heartburn and/or regurgitation) at least three days a week and have either no history of taking proton pump inhibitors, or PPIs, or a history of at least a partial symptom response to PPI therapy. Enrolled subjects must discontinue any prior therapy for GERD other than rescue antacids during a two-week washout period. During the second week of the washout period, baseline data regarding frequency and severity of GERD symptoms are assessed. Subjects are then randomized to one of five treatment arms: placebo; three dose levels of XP19986 (20 mg, 40 mg or 60 mg) administered once a day in the morning; or a fifth arm of XP19986 administered twice daily (30 mg BID). The treatment period is four weeks. The primary endpoint of the GERD Phase 2 clinical trial is the difference in the total number of episodes of heartburn experienced by each subject over the entire treatment period for the combined XP19986 dose groups versus the placebo group. XP19986 Phase 2 Clinical Trial in Spinal Cord Injury Patients with Spasticity XenoPort’s multiple-dose, randomized, placebo-controlled, crossover Phase 2 clinical trial of XP19986 is designed to evaluate the efficacy, safety and tolerability of a sustained-release formulation (designated as SR1) of XP19986 in patients with spasticity due to spinal cord injury. XenoPort believes that the SR1 formulation of XP19986, which provides sustained drug exposure over 12 hours, could provide improved therapy when dosed twice a day in spasticity patients who are underserved by current therapies that require dosing three or four times per day. The Phase 2 clinical trial is being conducted at multiple study centers in the United States. Three doses of XP19986 are being assessed in a randomized crossover comparison versus placebo. Twelve subjects will be enrolled in each dose level. Eligible subjects undergo a washout and baseline period, followed by XP19986 (10 mg, 20 mg or 30 mg) or placebo, administered twice a day in the first treatment segment. After a washout period, each subject receives the other treatment in the second treatment segment. The primary outcome measure in this study is the Ashworth Scale assessment of muscle tone. XP21279 Phase 1 Clinical Trial XenoPort’s randomized, double-blind, placebo-controlled single dose Phase 1 clinical trial is designed to assess the safety and pharmacokinetics (PK) of a prototype sustained-release formulation of XP21279 administered with carbidopa and to compare its PK profile to that of Sinemet (L-Dopa/carbidopa). Twelve healthy subjects will participate in a three-period study. Each subject receives two 250 mg tablets of XP21279 (216 mg-equivalent of L-Dopa) or placebo under fasted and fed conditions during the first two periods, followed by Sinemet (two 100 mg L-Dopa/25 mg carbidopa tablets) administered in an open-label manner in the same subjects in the third period. Subjects dosed with XP21279 receive two 25 mg Lodosyn (carbidopa) tablets every 12 hours on the day prior to, and on the day of, each treatment (except on the morning of Sinemet dosing). Blood and urine will be collected to determine the PK profile of XP21279, L-Dopa, L-Dopa metabolites and carbidopa. Preliminary PK results are expected in the first quarter of 2008. About XP19986 XP19986 is designed to overcome certain deficiencies of baclofen, a currently marketed generic drug approved for the treatment of spasticity. Baclofen is a racemic drug (a 50:50 mixture of R- and S-isomers). Studies have shown that the beneficial therapeutic properties of baclofen are attributable to the R-isomer of baclofen only. R-baclofen is a selective agonist of GABA-B receptors. Baclofen has a short half-life in blood after oral dosing, which necessitates frequent daily dosing and is associated with unwanted side effects. Absorption of baclofen in the colon is limited, which has prevented the development of a sustained-release formulation that could address these deficiencies. XP19986 is a new chemical entity that is a Transported Prodrug of R-baclofen. XP19986 is designed to engage natural nutrient transport mechanisms found on intestinal cell membranes, thereby gaining efficient entrance into the bloodstream. XP19986 is then rapidly converted to R-baclofen by high-capacity enzymes. In addition to R-baclofen, the metabolic breakdown products of XP19986 are natural substances with favorable safety characteristics. About XP21279 XP21279 is a Transported Prodrug of levodopa, or L-Dopa, one of the most effective therapies for reducing symptoms associated with Parkinson's disease, particularly in patients with severe Parkinson's disease. In spite of some improvements in L-Dopa therapy through co-administration of drugs designed to slow L-Dopa metabolism, L-Dopa therapy remains suboptimal due to fluctuations in L-Dopa blood concentrations between doses. To date, a satisfactory sustained-release formulation of L-Dopa has not been possible due to poor colonic absorption. XP21279 is a new chemical entity that is a Transported Prodrug of L-Dopa. XP21279 is designed to engage natural nutrient transport mechanisms located throughout the length of the gastrointestinal, or GI, tract, and then be rapidly converted to L-Dopa by the body's endogenous enzymes. In addition to L-Dopa, the metabolic breakdown products of XP21279 are substances with favorable safety characteristics. Because XP21279 is designed to be well absorbed from the lower GI tract, we believe it can be formulated for sustained release, thus reducing fluctuations of L-Dopa levels in the bloodstream. About XenoPort XenoPort, Inc. is a biopharmaceutical company focused on developing a portfolio of internally discovered product candidates that utilize the body’s natural nutrient transport mechanisms to improve the therapeutic benefits of existing drugs. XenoPort’s most advanced product candidate, XP13512, has successfully completed a pivotal trial in its Phase 3 clinical program for the treatment of RLS and has successfully completed a Phase 2a clinical trial for the management of PHN. XenoPort has also reported positive results from a Phase 2a clinical trial of its second product candidate, XP19986, in patients with GERD. To learn more about XenoPort, please visit the web site at www.XenoPort.com. Forward-Looking Statements This press release contains "forward-looking” statements, including, without limitation, all statements related to our and our partner’s future clinical development of XP13512 and the timing thereof; our future clinical development programs for XP19986 and XP21279 and the timing thereof; the release of additional clinical trial data and the timing thereof; the therapeutic and commercial potential of XP13512, XP19986 and XP21279; the suitability of XP19986 as a treatment for GERD and spasticity; the suitability of XP21279 as a treatment for Parkinson’s disease; the timing of future regulatory submissions, including the filing of a new drug application for XP13512 for RLS with the U.S. Food and Drug Administration; and our and our partner’s future clinical trials. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes,” "plans,” "expects,” "will,” "intends,” "potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon our current expectations. Forward-looking statements involve risks and uncertainties. Our actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks related to the uncertain results of clinical trials; our ability to successfully conduct the clinical trials for XP13512, XP19986 and XP21279 on the anticipated timeframes, or at all; our dependence on our current and additional collaborative partners; the uncertainty of the FDA approval process and other regulatory requirements and the uncertain therapeutic and commercial value of our compounds. These and other risk factors are discussed under the heading "Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2007, filed with the Securities and Exchange Commission on November 9, 2007. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based. XenoPort and Transported Prodrug are U.S. trademarks of XenoPort, Inc. Source code: XNPT2C