NS2359 is a triple monoamine reuptake inhibitor, which blocks the reuptake of dopamine, norepinephrine, and serotonin and may displace the dopamine reuptake inhibitor cocaine. NS2359 dissociates slowly from the transporters and has a long human half-life (up to 10 days) which makes frequent dosing unnecessary. NS2359’s pharmacological profile means that it may be able to reduce cocaine withdrawal symptoms, reduce cocaine craving and reduce cocaine-induced euphoria. In preclinical trials, NS2359 has been shown to reduce the reinforcing effects of cocaine and may have effects on cue induced drug craving. In a NIDA sponsored Phase 1 human laboratory interaction study, NS2359 was able to reduce the rewarding valence of 20 or 40 mg of cocaine, and it attenuated the cardiovascular effects of IV cocaine. Thus NS2359 does not show adverse interactions with cocaine. Furthermore, other human trials with NS2359 have shown that NS2359 has little or no abuse potential.
Cocaine dependence is a significant public health problem. In 2012, the National Survey on Drug Use and Health revealed that in the US 1.1 million persons were classified as dependent on or abusing cocaine. Cocaine abuse and dependence leads to significant morbidity and mortality. Other problems associated with cocaine use include increased rates of crime, violence, poverty, and family disruption. The standard treatment for cocaine dependence consists of individual and group psychotherapy and self-help groups. Although progress has been made in developing new psychosocial treatments, psychotherapy alone does not provide substantial benefit for many patients. Dropout rates in outpatient treatment programs are very high. Even among patients who complete treatment, relapse is common. Thus, medications have been sought to augment psychosocial treatment. Currently, there are no medications approved for the treatment of cocaine dependence. According to The Treatment Research Center (TRC) at University of Pennsylvania, the market value for an effective medication for cocaine addiction may exceed USD 1.8 billion in the U.S.
TRC is conducting an investigator-initiated clinical Phase 2a proof-of-concept study with NS2359 for treatment of cocaine addiction. The study is funded by non-dilutive grants from the Dana Foundation and the Groff Foundation. In January 2019, Saniona reported that based on an interim analysis of the blinded data for the first 50 patients enrolled, TRC plans to continue the cocaine addiction study with NS2359 at a higher dose. NS2359 appears to be well tolerated and data from other studies support the use of higher doses to exploit the full potential of the drug in this indication.
Saniona retains the commercial rights to NS2359 and the salt products are covered by issued patents in the U.S. expiring in 2028. In addition, the company expects to obtain data exclusivity, which provides protection in five years in the U.S. and ten years in Europe after market approval.
The Treatment Research Center (“TRC”) is a clinical outpatient treatment center that is part of the PENN/VA Center for the Studies of Addiction (CSA). TRC has a modern treatment facility with a fully certified clinical laboratory and a state of the art data management unit. The Investigators have been leaders in addiction pharmacotherapy research for over 35 years and highly experienced clinicians and research associates staff the center. TRC has an active recruitment process and network in place for cocaine addiction. The center screens about 250 cocaine dependent patients per year of which about 100 cocaine dependent patients are randomized into research protocols. TRC offers a comprehensive biopsychosocial evaluation in relation to clinical programs comprising a physical exam and ECG, an outpatient medical detoxification stabilization unit, and daily individual and group therapy sessions that are made available to patients eligible for one of the treatment-research studies.