Product Candidates
Patient Information

XP13512
Restless Legs Syndrome
Neuropathic Pain

XP13512 is a patented new chemical entity internally discovered at XenoPort. It is in clinical development for the potential treatment of restless legs syndrome, or RLS, and neuropathic pain.

XP13512 is our most advanced product candidate. It is a Transported Prodrug of gabapentin, a drug that has been sold by Pfizer Inc as Neurontin since 1993 and is currently sold as a generic drug by a number of companies. We believe that XP13512 addresses the deficiencies of gabapentin by targeting high-capacity nutrient transporter mechanisms expressed throughout the length of the intestines. We believe that this approach can overcome the variable and suboptimal exposure to gabapentin experienced by patients. In addition, by targeting transporters expressed throughout the length of the intestines, we have been able to develop a sustained-release formulation of XP13512 that we believe has overcome the need for frequent dosing of gabapentin.

XP13512 is designed to rapidly convert to gabapentin once absorbed from the GI tract, resulting in limited systemic exposure to the intact Transported Prodrug. In addition to producing gabapentin, XP13512 is metabolized to release other components with well-studied, favorable safety characteristics. We believe that XP13512 will have a favorable safety profile in humans, due to the inherently safe nature of gabapentin and the other metabolic breakdown products of XP13512.

Clinical Trials

Our Phase 1 clinical trials in healthy volunteers have demonstrated that, in contrast to gabapentin, oral administration of XP13512 produces dose-proportional blood levels of gabapentin across a broad range of doses. Additional Phase 1 clinical trials with a sustained-release formulation of XP13512 have demonstrated that, compared to equivalent doses of gabapentin, XP13512 produced higher levels of gabapentin in the blood for a longer period of time. XP13512 was well tolerated in all Phase 1 clinical trials. Furthermore, XP13512 was well tolerated at all doses tested with no serious adverse events.

We have successfully completed our Phase 2 clinical program of XP13512 for the treatment of RLS. We have also completed a successful Phase 2a trial of XP13512 for the management of post-herpetic neuralgia, or PHN, which is a type of neuropathic pain. This trial showed favorable results compared with both placebo and Neurontin (the tradename of gabapentin in the U.S. market), which is widely used to treat PHN. We have initiated Phase 3 clinical trials for the treatment of RLS that we believe could support an NDA filing and potential market approval of XP13512 for the treatment of RLS.

About Gabapentin

Gabapentin, a drug that is sold by Pfizer Inc as Neurontin, is approved for the management of post-herpetic neuralgia (PHN) and for the treatment of partial seizures. It is often prescribed by doctors to treat other neuropathic pain conditions, such as painful diabetic neuropathy, and is considered by many to be the gold standard for the treatment of neuropathic pain. Worldwide sales of Neurontin in 2004 were $2.7 billion. In late 2004, gabapentin became a generic drug.

Despite its commercial success, we believe that gabapentin therapy can be substantially improved. Studies have shown that as many as 70% of post-herpetic neuralgia patients do not respond to gabapentin therapy. Gabapentin absorption after oral administration is highly variable among patients, and there is a ceiling on the amount of gabapentin that can be absorbed due to a limitation of the absorption mechanism of the drug. XenoPort believes the limited and variable absorption of gabapentin contributes to lack of efficacy in some patients.

In addition, gabapentin's short half-life requires that it be administered three or four times a day, which may lead to poor compliance and reduced efficacy in some patients. Attempts to develop sustained-release formulations of gabapentin have failed because the drug is poorly absorbed in the colon, where sustained-release systems reside for the majority of time in their transit through the intestine.

XenoPort was recently issued U. S. Patent No. 6,818,787 covering composition of matter of XP13512.

We believe that XP13512 addresses the deficiencies of gabapentin by targeting high-capacity nutrient transporter mechanisms expressed throughout the length of the intestines.



XP13512
FACT SHEET