Product Candidates

XP19986
GERD
Spasticity

XP19986 is a patented new chemical entity discovered internally at XenoPort. It is in clinical development for the treatment of gastroesophageal reflux disease, or GERD and is also a potential treatment for the symptoms of spasticity. XP19986 is a Transported Prodrug of the R-isomer of baclofen. Baclofen is a generic drug that is currently approved to treat spasticity and has been shown in investigator-led studies to be effective in the treatment of GERD. XP19986 is designed to overcome the deficiencies of baclofen by targeting high-capacity nutrient transporter mechanisms expressed throughout the length of the entire GI tract, including the colon. By targeting these transporters, we believe that XP19986 can be formulated in a sustained-release pill and thereby require less frequent dosing than baclofen. Moreover, XP19986 produces only the R-isomer of baclofen, known as R-baclofen, while generic baclofen is racemic (contains a 50:50 mixture of the R- and S-isomers).

Once absorbed, XP19986 converts to R-baclofen and natural substances that have well-studied, favorable safety characteristics. We believe that the inherently safe nature of the metabolic breakdown products of XP19986 should provide XP19986 with a safety profile that is at least comparable to, and potentially better than, that seen with baclofen.

We have developed sustained-release formulations of XP19986 that may be suitable for once-daily or twice-daily dosing. We believe that XP19986, if successfully developed, may offer reduced dosing frequency, improved patient compliance, improved efficacy and/or reduced side effects.

Clinical Trials

We have reported positive preliminary data from a single dose Phase 2a clinical trial of XP19986 as a treatment for gastroesophageal reflux disease, or GERD. Our Phase 1 clinical trials showed that XP19986 was well tolerated under the tested conditions and that adverse effects were similar to those that have been previously reported for racemic baclofen. The trial also demonstrated that XP19986 was well absorbed and rapidly converted to the R-isomer of baclofen.

About Baclofen

Baclofen is an antispasticity agent that was originally approved in 1977 to ease the symptoms of spasticity in patients with multiple sclerosis and spinal cord injury. Although baclofen has acceptable oral bioavailability, its short plasma half-life necessitates dosing three to four times per day. This dosing regimen can produce peaks and troughs in a patient's exposure to the drug, which may result in side effects such as drowsiness and weakness during peak drug levels, and diminished efficacy during trough blood levels. Because baclofen is poorly absorbed in the colon, it cannot be effectively administered via a sustained-release dosage form since sustained-release systems rely on absorption of drug in the lower GI tract.

Recent studies have indicated that baclofen may be effective in treating GERD, through a novel mechanism of action. In many patients GERD is caused by inappropriate relaxation of the sphincter muscle that separates the stomach and esophagus, allowing stomach contents to enter the esophagus. Current approved drugs that treat GERD, such as proton pump inhibitors and H2 antagonists, reduce the acidity of stomach contents, thereby reducing the symptoms of GERD, especially heartburn. By contrast, we believe that XP19986 has the potential to reduce the inappropriate relaxation of the lower esophageal sphincter, and thereby reduce the reflux itself. As such, XP19986 may successfully treat symptoms associated with reflux of non-acidic stomach contents, for which proton pump inhibitors and H2 antagonists are ineffective.

We believe that XP19986 may treat the symptoms of GERD through an entirely new mechanism of action not currently used in GERD treatment today. It could also improve treatment of spasticity through improved pharmacokinetics over racemic baclofen.



XP19986
FACT SHEET