Pipeline

INDICATION:

Spinocerebellar ataxias (SCA) are a group of rare and ultra-rare progressively debilitating and fatal genetic conditions with no treatments available. SCA are characterized by progressive ataxia affecting coordination of hands, arms and legs as well as balance and speech. Patients experience significant morbidity, including progression to a wheelchair, impaired gait leading to falls, inability to communicate due to speech impairment, difficulty swallowing, and premature death. The range of symptoms and rate of progression of disease depend on the type of SCA, age of onset, and other factors. More than 40 different types of SCA are now recognized. SCA3 (Machado-Joseph Disease) is the most prevalent form of SCA worldwide, representing 30 to 50% of patients.

RATIONALE:

Troriluzole is a new chemical entity (“NCE”) and tripeptide prodrug of the active metabolite, riluzole. Troriluzole is optimized for improved bioavailability, pharmacokinetics, tolerability, and dosing compared to its active metabolite. Based on its mechanism of action, preclinical data and clinical studies, troriluzole has potential for therapeutic benefit in a range of neurological and neuropsychiatric illnesses. Initial development focused on SCA, based on two prior randomized controlled trials conducted by third parties that demonstrated preliminary efficacy of riluzole in the treatment of patients with ataxia.

Troriluzole has received orphan drug designation from the U.S. Food and Drug Administration for the treatment of SCA.

INDICATION:

Obsessive-Compulsive Disorder (OCD) is a chronic neuropsychiatric disorder characterized by symptoms of obsessions (intrusive thoughts) and compulsions (repetitive behaviors) that can interfere with patients’ functional abilities. According to the National Institute of Mental Health, the 12-month prevalence of OCD is 1% of the U.S. adult population, and approximately half of these cases are characterized as severe. Despite the significant public health burden, no novel mechanisms of action have been approved by the FDA for OCD in over two decades. First-line treatment for OCD includes cognitive behavioral therapy, selective serotonin reuptake inhibitors and adjunctive use of atypical antipsychotics. Nonetheless, up to 60% of patients have an inadequate response to conventional intervention strategies and some seek invasive neurosurgical procedures to ameliorate symptoms.

RATIONALE:

Troriluzole is a new chemical entity (“NCE”) and tripeptide prodrug of the active metabolite, riluzole. Troriluzole is optimized for improved bioavailability, pharmacokinetics, tolerability, and dosing compared to its active metabolite. Based on its mechanism of action, preclinical data and clinical studies, troriluzole has potential for therapeutic benefit in a range of neurological and neuropsychiatric illnesses. The rationale for use of troriluzole in OCD is supported by clinical data with its active metabolite, riluzole, in populations with OCD in open-label and placebo-controlled clinical trials as well as in preclinical, genetic and neuroimaging studies implicating the glutamatergic hyperactivity in the pathogenesis of OCD.

Phase 2/3 study results demonstrated that troriluzole administered once daily as adjunctive therapy in OCD patients with inadequate response to standard of care showed consistent numerical improvement over placebo on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) at all study timepoints (weeks 4 to 12). While the primary outcome measure at week 12 (p = 0.22 at week 12) was not met, it was significant at week 8 (p = 0.05). Given the strong signal in the Phase 2/3 proof of concept study, a Phase 3 program was initiated.