SD-809: A VMAT-2 Inhibitor for the Treatment of Hyperkinetic Movement Disorders—Lead Program (Phase 3 Ongoing)

Our lead product candidate, SD-809, is in a Phase 3 registration clinical trial for the treatment of chorea (abnormal involuntary movements) associated with Huntington’s disease. Tetrabenazine (marketed as Xenazine® in the United States) is the only therapy approved by the U.S. Food and Drug Administration, or FDA, for this indication. Using our deuterium technology, we made chemical modifications at specific positions in the tetrabenazine molecule to create the novel drug candidate SD-809 (dutetrabenazine). Deuterium is a non-toxic, naturally occurring form of hydrogen. The substitution of deuterium (2H) for hydrogen (1H) at specific positions, in the case of SD-809, attenuates the breakdown of the drug’s active metabolites resulting in a differentiated pharmacokinetic profile compared to tetrabenazine. This profile should enable less frequent dosing, improved tolerability, reduced interpatient variability in drug metabolism, as well as reduced drug interactions and reduced need for genotyping for drug-metabolizing enzymes. We believe that this profile will allow SD-809 to address unmet needs in a variety of hyperkinetic movement disorders.

We have completed several Phase 1 clinical trials for SD-809 which demonstrate that, compared to tetrabenazine, it has a differentiated pharmacokinetic profile. Our ongoing development program for SD-809 for the treatment of chorea associated with Huntington’s disease is in Phase 3 development. Our Phase 3 registration clinical trial in this indication, which we refer to as First-HD, is designed to evaluate, and generate label information for, the safety, tolerability and efficacy of SD-809 for treating chorea associated with Huntington’s disease. We expect that data from First-HD will be available in the second half of 2014. We have also initiated an open-label clinical trial, which we refer to as ARC-HD that will evaluate long-term safety as well as provide guidance on how to switch patients who are currently on tetrabenazine to SD-809. We are also planning a Phase 2/3 efficacy clinical trial of SD-809 for the treatment of tardive dyskinesia and a Phase 1b clinical trial of SD-809 for the treatment of tics associated with Tourette syndrome.

Deuterium-containing pirfenidone analog (SD-560)

SD-560 is intended for the treatment of idiopathic pulmonary fibrosis. Pirfenidone is marketed in Japan and the European Union for this indication but has limited efficacy, significant side effects and must be taken three times daily. Auspex believes that SD-560 will have significant benefits over pirfenidone in efficacy as well as safety and compliance.

Deuterium-containing ticagrelor analog (SD-970)

SD-970 is intended for the treatment of acute coronary syndrome. Ticagrelor (Brilinta®) is AstraZeneca’s new anti-platelet drug that was recently approved in the EU and US. Auspex believes that SD-970 will combine the reversible inhibition of Brilinta with the once-daily dosing schedule of its competitor Plavix, to create the best-in-class drug for acute coronary syndrome.

Deuterium-containing tofacitinib analog (SD-900)

SD-900 is intended for the treatment of rheumatoid arthritis (RA). Tofacitinib is Pfizer’s oral JAK inhibitor that has recently been approved by the FDA for the treatment of RA. It is generally taken twice daily and has a limited therapeutic window. Auspex believes that the increased half-life of SD-900 may enable the development of a once-daily compound with the potential for enhanced safety compared to tofacitinib.

Deuterium-containing venlafaxine analog (Effexor™) (SD-254)

SD-254 is a selective serotonin-norepinephrine reuptake Inhibitor (SSNRI). SD-254 has several important advantages over venlafaxine, and Auspex is primarily interested in developing the compound for the treatment of neuropathic pain. SD-254 has completed phase 1 clinical testing and demonstrates a major increase in drug exposure together with less metabolic variability compared to venlafaxine itself.