MILWAUKEE, Wis.—Promentis Pharmaceuticals announced that it has completed Phase 1 single ascending dose and multiple ascending dose studies for its lead compound, SXC-2023, which has demonstrated a compelling profile across a range of non-clinical studies. Promentis is developing SXC-2023 and other compounds that engage System xc-, a central nervous system (CNS) target addressing glutamatergic imbalance and oxidative stress, in order to treat impulse control disorders, obsessive-compulsive disorder and other neuropsychiatric diseases.
The aim of the Phase 1 studies was to evaluate the safety, tolerability and pharmacokinetic (PK) profile of single and multiple ascending oral doses of SXC-2023. In the first study, single ascending doses were evaluated in six cohorts, with a total of 48 subjects. In the second study, SXC-2023 was administered daily for 14 days within four different dose groups. SXC-2023 proved to be safe and well-tolerated over a wide dose range in healthy volunteers in both the SAD and MAD studies, and demonstrated a very consistent PK profile. There were no significant adverse events and no treatment-related discontinuations in either study.
“We are very pleased with these results, which show SXC-2023 to be very safe and well-tolerated, and to possess a very well-behaved PK profile,” said Dr. Tom Beck, CMO of Promentis. “We believe that the mechanism and excellent safety profile of the drug are consistent with potential applications in a wide variety of impulse control disorders, both as monotherapy and in combination with other treatments. These results reinforce our interest and enthusiasm in SXC-2023 as we look to the near-term commencement of our Phase 2 program.”
Glutamatergic dysfunction is a hallmark feature of many neuropsychiatric indications, including a broad range of impulse control disorders (ICDs), which is Promentis’s initial therapeutic focus.
Promentis’s first ICD monotherapy indication is trichotillomania, a disabling and under-recognized condition characterized by recurrent hair pulling. Trichotillomania is more common in women than men, and has been estimated to affect approximately 1% of the US population. No medications are approved by the US Food and Drug Administration for the treatment of this chronic disorder.
Obsessive-compulsive and related disorders, as defined by DSM-5, represents a broad category of neuropsychiatric disease, including OCD, excoriation (skin-picking) disorder and trichotillomania. Trichotillomania is characterized by recurrent hair pulling despite repeated attempts to stop the behavior, leading to noticeable hair loss. Trichotillomania is associated with a range of psychosocial problems, including low self-esteem, social anxiety, avoidance of intimacy, occupational impairment and an overall decrease in quality of life. In addition, a significant number of trichotillomania patients ingest their hair after pulling, which can lead to life-threatening gastrointestinal blockages which require surgery.
Alterations in glutamate signaling within brain regions implicated in urge control and executive function have been proposed to contribute to the underlying pathology of trichotillomania, as well as other obsessive-compulsive disorders, addictive disorders and other CNS conditions. Obsessive-compulsive disorder is the Promentis’s first add-on indication, and the company is also exploring additional CNS indications where glutamatergic imbalance and oxidative stress contribute to impaired functioning.