Saniona AB: Saniona's partner TRC initiates Phase 2a study for NS2359 in cocaine addiction

9 juni 2016

PRESS RELEASE

June 9, 2016

Saniona, a leading biotech company in the field of ion channels, today announces that the University of Pennsylvania Treatment Research Center (TRC) has initiated recruitment of patients in a Phase 2a study for Saniona's compound, NS2359, for treatment of cocaine addiction. Today there are no approved drugs to treat cocaine addiction. The trial comprises a total of up to 80 patients.

"We are very excited about the initiation of this important Phase 2a study. TRC is world class within clinical trials on drug addiction. The two principal investigators are recognized leaders in addiction research. Dr. Berrettini is an internationally-recognized expert in the genetics of addiction and Dr. Kampman is a highly respected top researcher in conducting clinical studies of cocaine addiction. TRC has secured funding for initiation of this trial which demonstrates their commitment and belief in the concept" says Jørgen Drejer, CEO of Saniona.

"Cocaine addiction is a significant public health problem, responsible for substantial medical, psychiatric, and economic costs. There are no medications proven efficacious for the treatment of cocaine addiction. The development of an effective pharmacotherapy for cocaine-addicted patients has the potential to significantly impact the public health by addressing the needs of hundreds of thousands of Americans," says Kyle M. Kampman, MD, Medical Director of the TRC.

"We are eagerly looking forward to test NS2359 for treatment of cocaine addiction. The scientific rational is clear and supported by preclinical and clinical evidence. We believe that NS2359 may be able to reduce cocaine craving and blunt the euphoric effects of cocaine without causing euphoria itself. Therefore, NS2359 represents a very promising candidate, which would be the first approved drug to treat cocaine addiction," says Dr. Wade Berrettini, principal investigator at University of Pennsylvania.

The study is conducted by TRC at the University of Pennsylvania's treatment facility at the PENN / VA Center for the Studies of Addiction (CSA). The primary objective of the Phase 2a study is to examine whether NS2359 leads to abstinence from cocaine during the last 2 weeks of treatment. The secondary objective is to investigate whether NS2359 provides a reduction in craving for more cocaine, a reduction in withdrawal symptoms, a reduction in alcohol consumptions and smoking and whether NS2359 provides improved cognitive ability. The double blind, placebo controlled study comprises a total of up to 80 patients, where half of the patients will receive NS2359 and half of the patients will receive matching placebo for a total of 8 weeks.  All patients will be offered weekly individual therapy sessions in relation to the trial. Further details about the trial will be made available at https://clinicaltrials.gov/.

The study is supported by grants from the Dana Foundation and the Groff Foundation.

For more information, please contact

Thomas Feldthus, EVP and CFO, Saniona, Mobile: +45 2210 9957, E-mail: tf@saniona.com

About Saniona

Saniona is a research and development company focused on drugs for diseases of the central nervous system, autoimmune diseases, metabolic diseases and treatment of pain. The company has a significant portfolio of potential drug candidates at pre-clinical and clinical stage. The research is focused on ion channels, which makes up a unique protein class that enables and controls the passage of charged ions across cell membranes. Saniona has ongoing collaboration agreements with Upsher-Smith Laboratories, Inc., Productos Medix, S.A de S.V and Saniona's Boston based spinout Ataxion Inc., which is financed by Atlas Venture Inc. and Biogen Inc. Saniona is based in Copenhagen, Denmark, where it has a research center of high international standard. Saniona is listed at Nasdaq First North Premier and has about 4,400 shareholders. Pareto Securities is Certified Advisor for Saniona. The company's share is traded under the ticker SANION. Read more at www.saniona.com .

About NS2359

NS2359 is a triple reuptake inhibitor, which blocks the reuptake of dopamine, norepinephrine, and serotonin in a similar manner to cocaine. However, NS2359 dissociates slowly from these transporters and has a long human half-life (up to 10 days) which makes frequent dosing unnecessary. NS2359s 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. Furthermore, human trials with NS2359 have shown that NS2359 has little abuse potential and does not have adverse interactions with cocaine.  Thus, NS2359 is a very promising medication for the treatment of cocaine dependence.

About the Treatment Research Center at the University of Pennsylvania, TRC

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 screen 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.

Further details about NS2359 and cocaine addiction

Cocaine addition

Cocaine dependence continues to be a significant public health problem. In 2012, the National Survey on Drug Use and Health revealed that in the US 639,000 persons used cocaine or crack cocaine for the first time, 1.6 million people had used cocaine at least once during the month prior to the survey, and 1.1 million persons were classified as dependent on or abusing cocaine. Cocaine abuse and dependence leads to significant morbidity and mortality. Medical problems associated with cocaine use include an increased risk of HIV, hepatitis, and serious pulmonary and cardiovascular disease ^[i] . Other problems associated with cocaine use include increased rates of crime, violence, poverty, and family disruption ^[ii] . 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 for cocaine dependence, psychotherapy alone does not provide substantial benefit for many patients ^[iii] . Dropout rates in outpatient treatment programs are very high ^[iv] . Even among patients who complete treatment, relapse is common ^[v] . Thus, medications have been sought to augment psychosocial treatment. Currently, there are no medications approved for the treatment of cocaine dependence.

Mode of action and rationale for treatment of cocaine addiction

NS2359 is a triple reuptake inhibitor, which blocks the reuptake of dopamine, norepinephrine, and serotonin in a similar manner to cocaine. Compared to cocaine, NS2359 has greater affinities at the three transporters. However, in contrast to cocaine, NS2359 dissociates slowly from all three transporters and it has a very long human half-life (up to 10 days). Therefore, NS2359 has the potential to block binding of cocaine to these transporters and blunt cocaine reward, even with episodic non-compliance. Furthermore, it may be able to blunt cocaine withdrawal symptoms, which have been associated with reduced dopamine and serotonin activity in newly abstinent cocaine dependent patients ^[vi] . In addition, as a long acting medication with a mechanism of action similar to that of cocaine, NS2359 may be able reduce cocaine craving and blunt the euphoric effects of cocaine without causing euphoria itself.

Effective medications exist for the treatment of nicotine addiction and opioid addiction. These effective medications have the ability to do one or more of three things: 1) reduce drug withdrawal symptoms, 2) reduce drug craving, and 3) reduce the euphoria associated with the abused drug. The pharmacological profile of NS2359 suggest that NS2359 may fulfil all three characteristics for an effective medication for cocaine addiction. NS2359 has the potential to reduce cocaine withdrawal symptoms (characterized by deficient mono-amine transmission in key brain areas); reduce cue-induced drug cravings; and prevent the euphoria induced by cocaine. NS2359 has a unique long human half-life (up to 10 days) which makes frequent dosing unnecessary. 

Preclinical and clinical evidence for treatment of cocaine addiction

In preclinical studies, NS2359 has demonstrated clear efficacy against cocaine craving behavior in cocaine dependent rodents and monkeys. Preclinical studies have shown that NS2359 reduces cocaine self-administration in Rhesus monkeys and substitutes for cocaine in both rat and monkey drug-discrimination.

NS2359 was originally developed under an agreement with NIDA for the treatment of cocaine addiction.   NeuroSearch discontinued the agreement with NIDA in relation to the outlicense of NS2359 to GlaxoSmithKline in 2004. GlaxoSmithKline performed additional non-clinical and clinical studies under the name GSK372475 in order to investigate NS2359's potential as an antidepressant agent and for the treatment of adults with ADHD. NeuroSearch regained the rights to NS2359 from GlaxoSmithKline in 2009 since the Phase 2 studies indicated that NS2359 had no advantage over current treatment for major depression disorders and adult with ADHD. In total NS2359 has been administered to more than 600 individuals as part of eleven Phase 1 studies (5 single dose and 6 repeat-dose studies) and three Phase 2 studies. These studies indicate that the drug is safe and well tolerated in humans for administration up to 10 weeks. These studies provide also promising evidence for using NS2359 as a treatment for cocaine dependence. NS2359 did not cause euphoria in any of the multiple Phase 1 studies or the Phase 2 clinical trials for major depressive disorder ^[vii] and adult attention deficit disorder ^[viii] . Furthermore, in a human laboratory drug discrimination study, NS2359 exhibited no abuse liability in comparison with 15 or 30 mg of amphetamine. 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.

Saniona development strategy for NS2359

Based on NS2359's pharmacological profile and the promising preclinical and clinical studies, the University of Pennsylvania's Treatment Research Center (TRC) intend to perform a clinical proof-of-concept study with NS2359 for treatment of cocaine addiction, where the rationale is very strong, the medical need substantial and the market potential significant. Saniona and TRC intend to apply for additional public funding to continue the development of NS2359 if the trial proves to be successful. Saniona retains the commercial rights to NS2359.

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