Products & Intellectual Property
Our company’s first technology is an in-licensed chemical library of potent and selective modafinil analogues developed by investigators Amy Newman, Jianjing Cao, and Oluyomi Okunola-Bakare at the National Institute on Drug Abuse (NIDA) (Intellectual Property: US Application No. 61/774,878). These compounds offer a wide range of competitive pharmacokinetic advantages over the parent drug modafinil and other drugs currently being evaluated as treatments for psychostimulant use disorders. EncepHeal is interested in and is capable of collaborative research with NIDA to further evaluate and commercialize a select number (1-3) of these compounds as potential therapeutic agents for the treatment of psychostimulant abuse and addiction. Modafinil, the parent drug, is a wake-promoting prescription medication that is approved by the Food and Drug Administration for the treatment of narcolepsy and other sleep disorders. Currently, modafinil is being investigated as a treatment for psychostimulant (cocaine and methamphetamine) addiction. Like cocaine and methamphetamine, modafinil’s primary biological target is the dopamine transporter (DAT); however, it binds the DAT differently than cocaine and shows no evidence of abuse liability in humans (Loland et al, 2012; Mereu et al, 2013). Early clinical trials reported that modafinil successfully reduced cocaine intake and prevented relapse more effectively than placebo treatments (Dackis et al, 2005; Hart et al, 2008). Yet, larger and more recent multi-center trials have reported only modest advantages of modafinil over placebo in promoting cocaine abstinence (Anderson et al, 2009; Dackis et al, 2012). It is clear that modafinil - which is water-insoluble, displays relatively low inherent binding affinity for the DAT, and must therefore be administered in large doses (up to 400 mg/day) in order to achieve its therapeutic effects - leaves much to be desired as a stand-alone pharmacotherapy to treat psychostimulant addictions.The modafinil analogues synthesized at NIDA offer significant pharmacokinetic improvements over the parent drug while retaining its atypical (non-addictive) DAT binding profile (Okunola-Bakare et al, 2014). Furthermore, these new compounds display significantly higher binding affinity for the DAT (up to 20-fold) with enhanced selectivity for the DAT over other monoamine transporters (up to 2,900-fold increases in SERT:DAT and NET:DAT affinity ratios) compared to modafinil. Lastly, salts of these newly-synthesized amine compounds present a significant solubility advantage over the non-aminergic and water-insoluble parent drug. Altogether, these more potent analogs offer greater bioavailability and lower effective doses for the avoidance of side effects.
Brief History of Psychostimulant Addiction
Cocaine addiction started becoming prominent in the 1970s when drug cartels in South America began mass producing the drug and exporting it to the United States. Since then, the problem has progressively gotten worse. Today, over four million people in the U.S. are in need of treatment. Likewise, addiction to amphetamine is on the rise, with more than three million Americans suffering from them. When cocaine and amphetamine enter the bloodstream, the drugs interfere with the brain’s dopamine transporter (DAT), the protein responsible for removing dopamine from the neural synapses and storing it back into the nerve cells. By blocking the DAT, psychostimulants keep dopamine in our systems and produce intense feelings of euphoria. There are nearly 8 million people in the United States in need of treatment for a psychostimulant addiction; however, there are no FDA approved drugs on the market. There is a need to develop a new, first-in-class treatment to help these people that have long been neglected.
Changing Landscape of Addiction
Since Nixon’s war on drugs in the 1970s, the tendency has been to persecute those with addictions instead of treating them. However, scientists have since established that substance abuse is a disease that causes specific changes in the brain and are discovering possible ways to treat those suffering from addictions. The addiction landscape is changing in a number of ways: - The DSM-V now lists addiction as a treatable medical disorder, opening the door for pharmacotherapies. - The Affordable Care Act mandates that any therapeutics to treat substance abuse therapeutics be covered by insurance companies. - There has been vast decriminalization of drug-related crimes and more advocation for treatment rather than persecution.