XenoPort Announces Results of a Phase 1 Clinical Trial and Plans for Additional Phase 2 Clinical Trials of XP19986

XenoPort, Inc. (Nasdaq:XNPT) today announced results of a placebo-controlled, dose-escalating, repeat-dose Phase 1 clinical trial of XP19986 formulated in a sustained-release tablet, designated as SR3. The trial demonstrated sustained levels of XP19986 over 24 hours and enabled identification of suitable doses for further clinical studies of XP19986. XenoPort plans to initiate a Phase 2 clinical trial of the XP19986 SR3 formulation in gastroesophageal reflux disease (GERD) patients later this year. In addition, XenoPort plans to initiate later this year a Phase 2 clinical trial in patients with spasticity that will be conducted with a second formulation of XP19986, designated as SR1. Ronald W. Barrett, Ph.D., XenoPort's chief executive officer, stated, "We are very pleased to be reporting these advancements in our XP19986 program. This Phase 1 clinical trial with the SR3 formulation of XP19986 has furthered our understanding of the steady-state drug levels that we are able to obtain with XP19986 and has positioned us to test this formulation in a GERD symptom study.” Phase 1 Clinical Trial Results The objective of the Phase 1 clinical trial was to assess the safety, tolerability and pharmacokinetics of the SR3 formulation of XP19986 dosed once (QD) or twice (BID) daily in healthy adult volunteers. The trial was conducted sequentially in four separate cohorts of 12 subjects, three of whom received placebo per cohort. Following an up-titration period, the first cohort received 30 mg QD of XP19986 for seven days, followed by 30 mg BID for seven days and ending with a down-titration period. Subsequent cohorts received 60 mg and 90 mg QD and BID following a similar protocol. The final group of subjects received 120 mg QD only. Subjects were monitored for adverse events, and blood and urine were sampled to determine pharmacokinetic profiles and bioavailability. The trial demonstrated that repeated QD dosing of XP19986 resulted in sustained levels of R-baclofen in blood over 24-hours, which reached steady-state within three days. Repeated BID dosing reduced the steady-state peak-to-trough ratio of R-baclofen by approximately 50% compared to QD dosing. Exposure to R-baclofen increased linearly with dose. The Phase 1 clinical trial also indicated that XP19986 was well tolerated under the tested conditions. All reported adverse effects were consistent with those previously reported for racemic baclofen. The most commonly reported adverse events were somnolence, dizziness and nausea that were generally mild in severity and generally increased in incidence compared to placebo with daily doses above 60 mg. In the 120 mg cohort, one subject experienced episodes of slurred speech and tremor, which are reported side effects of baclofen. This subject received medical treatment, discontinued dosing and was reported as a serious adverse event case. "We are encouraged by the results of this repeat-dose Phase 1 clinical trial of the SR3 formulation of XP19986," said Dr. Barrett. "The steady-state pharmacokinetic data from this study reinforces our belief that once-a-day treatment with the XP19986 SR3 formulation may be possible. While this study was conducted in healthy subjects, the data suggests that a sustained-release formulation of XP19986 could deliver therapeutic exposures of R-baclofen in GERD and spasticity patients while maintaining good tolerability.” Planned XP19986 Phase 2 Clinical Trial in Patients with GERD XenoPort plans to initiate later this year a randomized, parallel-group, double-blind, placebo-controlled Phase 2 clinical trial of the efficacy, safety and tolerability of the SR3 formulation of XP19986 in subjects with symptomatic GERD. The study is expected to be conducted in approximately 150 patients at multiple study centers in the United States. In this planned study, eligible GERD patients will have been diagnosed by a gastroenterologist and have symptoms (heartburn and/or regurgitation) at least three days a week. Patients will have either no history of taking proton pump inhibitors (PPIs), or a history of at least a partial symptom response to PPI therapy. Patients will 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 will be assessed. Patients will then be randomized to one of five treatment arms: placebo; three dose levels of XP19986 administered once-a-day in the morning; and a fifth arm of XP19986 administered twice daily. The treatment period will be four weeks. The planned primary endpoint of the GERD Phase 2 clinical trial will be the difference in the total number of episodes of heartburn experienced by each patient during the entire treatment period for the combined XP19986 dose groups versus the placebo group. Planned XP19986 Phase 2 Clinical Trial in Patients with Spasticity XenoPort also plans to conduct a multiple-dose, randomized, placebo-controlled, crossover Phase 2 clinical trial of the efficacy, safety and tolerability of a BID formulation (SR1) of XP19986 in subjects with spasticity due to spinal cord injury. XenoPort believes that the SR1 formulation of XP19986, that 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 study is expected to be conducted at multiple study centers in the United States. In this planned study, three doses of XP19986 will be assessed in a randomized crossover comparison versus placebo. Each dose level will be evaluated in 12 subjects. Eligible patients will undergo a washout and baseline period, followed by XP19986 or placebo twice a day in the first treatment segment. After a washout period, each patient will receive the other treatment in the second treatment segment. The planned primary outcome measure in this study will be the Ashworth Scale assessment of muscle tone. About XP19986 XP19986 is designed to overcome the 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. XP19986 is the subject of an issued composition-of-matter patent in the United States, which expires in 2025, and patent applications throughout the world. About GERD GERD is a digestive system disorder caused in many patients by inappropriate relaxations of the lower esophageal sphincter, which is a combination of muscles that controls the junction between the esophagus and the stomach. GERD is characterized by the frequent, undesirable passage of stomach contents into the esophagus that results in discomfort and potential damage to the lining of the esophagus. More than $10 billion is spent worldwide each year on GERD and heartburn medications, and approximately 6% of the global population experiences GERD symptoms daily. Conventional treatment for GERD includes medications that suppress stomach acid, including proton pump inhibitors and H2-receptor antagonists, as well as over-the-counter antacids. However, these treatments are not effective in all patients, and there is a subset of patients who suffer from reflux of stomach contents that are not acidic who do not respond to these acid suppression treatments. Preclinical and clinical data conducted with racemic baclofen or R-baclofen suggests that activation of GABA-B receptors may be effective in treating GERD. Unlike acid suppressing agents, R-baclofen exerts its effects on the function of the lower esophageal sphincter that controls passage of material between the esophagus and the stomach. R-baclofen reduces the frequency of transient lower esophageal sphincter relaxations and, therefore, passage of gastric contents into the esophagus, and may potentially be effective, alone or in combination with acid suppressants, in providing symptomatic relief. About Spasticity Spasticity is a widespread and debilitating condition that is associated with some common neurological disorders, such as spinal cord injury, multiple sclerosis, stroke and cerebral palsy. Spasticity is a condition in which certain muscles are continuously contracted, causing stiffness or tightness of muscles that interferes with movement or speech. Reports indicate that the prevalence of spasticity due to multiple sclerosis, stroke and cerebral palsy in 2002 was approximately 5.2 million patients in the United States and six other major pharmaceutical markets, collectively. For the 12 months ended June 30, 2007, there were approximately 3.6 million prescriptions written for baclofen in the United States. According to data on baclofen prescriptions, multiple sclerosis, spinal disease/injury, pain conditions and spasm conditions accounted for 80% of baclofen use. Besides baclofen, treatments for spasticity include diazepam, tizanidine and dantrolene sodium. Although these medications may provide symptomatic relief in some people, they are often only partially effective and generally require dosing three or more times a day. In addition, these medications are often associated with unwanted side effects, such as sedation and weakness, as well as issues with bladder, bowel and sexual function. 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 restless legs syndrome and has successfully completed a Phase 2a clinical trial for the management of post-herpetic neuralgia. XenoPort has also reported positive results from a Phase 2a clinical trial of its second product candidate, XP19986, in patients with gastroesophageal reflux disease. 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 future clinical development of XP19986 and the timing thereof; the therapeutic and commercial potential of XP19986; the suitability of XP19986 as a treatment for GERD or spasticity; and our 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,” "anticipates,” "plans,” "expects,” "will,” "intends,” "suggests,” "potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon XenoPort’s current expectations. Forward-looking statements involve risks and uncertainties. XenoPort’s 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, the ability of the company to successfully conduct clinical trials for XP13512 and XP19986 and the uncertainty of the timing and results thereof; the uncertainty of the FDA approval process and other regulatory requirements; our dependence on our current and additional collaborative partners; and the therapeutic and commercial value of the company’s 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 June 30, 2007, filed with the Securities and Exchange Commission on August 9, 2007. XenoPort expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in the company’s 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. XNPT2C