Opiant Pharmaceuticals Announces First Patient Dosed in Phase 2 Trial of OPNT002, Nasal Naltrexone, for Alcohol Use Disorder

• Phase 2 trial to evaluate reduction in heavy drinking as measured by a change in the World Health Organization drinking risk levels¹
• Trial is informed by results from Phase 1 studies that showed pharmacokinetic properties of OPNT002 well suited for ‘as needed’ administration, either in anticipation of drinking or once drinking has started^2,3
• Target enrollment of approximately 300 patients; Results anticipated in 2023
• Alcohol Use Disorder is a chronic relapsing brain disease characterized by compulsive heavy drinking and is among the most prevalent mental health disorders globally⁴

SANTA MONICA, Calif., Jan. 20, 2022 (GLOBE NEWSWIRE) — Opiant Pharmaceuticals, Inc. (“Opiant”) (NASDAQ: OPNT) today announced that the first patient has been dosed in a Phase 2 clinical trial of OPNT002, nasal naltrexone, for the treatment of Alcohol Use Disorder (“AUD”). The trial will determine whether OPNT002 reduces heavy drinking as measured by a change in the World Health Organization (“WHO”) drinking risk levels¹.

“The development of OPNT002 is predicated on modifying a patient’s drinking behavior in order to reduce the harm of alcohol,” said Phil Skolnick, Ph.D., D.Sc. (hon.), Chief Scientific Officer of Opiant. “Compelling clinical data have shown that reducing drinking from very high levels to more moderate levels can reduce long-term mortality and overall disease burden.”

Clinical and preclinical studies have shown that alcohol releases endorphins, which are the brain’s endogenous opioids. These endorphins are thought to activate opioid receptors, which contribute to alcohol’s reinforcing and addictive properties. Current naltrexone treatments work to block mu-opioid receptors when administered orally or through injection. However, converging lines of evidence indicate that activation of delta-opioid receptors also contributes to the reinforcing properties of alcohol. The effective blockade of delta‐opioid receptors requires much higher plasma naltrexone concentrations than is achieved by currently approved naltrexone products⁵.

Opiant is developing OPNT002 to rapidly increase plasma concentrations of the drug following dosing and thereby block mu and delta-opioid receptors. In previous research, OPNT002 has demonstrated rapid nasal absorption, delivering high levels of naltrexone yet with a short half-life. Results from Phase 1 studies demonstrate that OPNT002 produces maximum plasma concentrations that are approximately 50% higher than orally administered naltrexone. This feature, along with a very rapid onset and a short plasma half-life, are characteristics ideally suited to developing OPNT002 for ‘as needed’ nasal dosing in anticipation of drinking, or once drinking has started^2,3. The primary end point will be the proportion of subjects showing an improvement in WHO Drinking Risk Level consisting of a 2-level reduction from Baseline to end of treatment. WHO Drinking Risk Level will be evaluated in the 28 days prior to the Baseline and end of treatment visits.

The trial is a randomized, double-blind, placebo-controlled study that will enroll approximately 300 patients at sites within the European Union and the United Kingdom. The trial features a Sequential Parallel Comparison Study Design (“SPCD”) aiming to reduce placebo response. Results from the trial are expected in 2023.

“Multiple medications are approved for the treatment of AUD, yet less than 10% of individuals with AUD currently receive treatment,” said Roger Crystal MD, President and Chief Executive Officer of Opiant. “For those suffering from AUD, current therapies and treatments are built around an endpoint of abstinence, rather than harm reduction. The availability of a treatment option in the event a person craves alcohol, anticipates drinking or finds themselves in a high-risk situation such as a party or restaurant setting is an approach we believe could increase the number of people using medication.”

About Alcohol Use Disorder
Alcohol Use Disorder is a chronic relapsing brain disease characterized by compulsive use of alcohol and the inability to control intake. It is the third leading preventable cause of death in the United States, and according to the World Health Organization, harmful use of alcohol is responsible for 5.1% of the global burden of disease^6,7. A report by the Centers for Disease Control and Prevention, found that deaths from alcohol use increased by 43 percent from 2006 to 2018⁸. Another study published in the JAMA network about changes in alcohol use during the COVID-19 pandemic said compared to 2019, American adults have increased their alcohol intake in 2020, by 14 percent⁹.

About Opiant Pharmaceuticals, Inc. 
Opiant Pharmaceuticals, Inc., the company that developed NARCAN® Nasal Spray, is building a leading franchise of new medicines to combat addictions and drug overdose.
For more information visit: www.opiant.com.

Forward-Looking Statements
This press release contains forward-looking statements, including the anticipated results of the Phase 2 study in 2023. These statements relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our or our industry’s actual results, levels of activity, performance or achievements to be materially different from any future results, levels of activity, performance or achievements expressed, implied or inferred by these forward-looking statements, and among other things, our ability to maintain cash balances and successfully commercialize or partner our product candidates currently under development. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “could,” “would,” “expects,” “plans,” “intends,” “anticipates,” “believes,” “estimates,” “predicts,” “projects,” “potential,” or “continue” or the negative of such terms and other comparable terminology. These statements are only predictions based on our current expectations and projections about future events. You should not place undue reliance on these statements. Actual events or results may differ materially. In evaluating these statements, you should specifically consider various factors. Additional factors that could materially affect actual results can be found in our Form 10-K for the year ended December 31, 2020, filed with the Securities and Exchange Commission on March 4, 2021, including under the caption titled “Risk Factors.”  These and other factors may cause our actual results to differ materially from any forward-looking statement. We undertake no obligation to update any of the forward-looking statements after the date of this press release to conform those statements to reflect the occurrence of unanticipated events, except as required by applicable law.

For Media and Investor Inquiries:
Ben Atkins, Opiant
(310) 598-5410
batkins@opiant.com

Sources:

1.   Witkiewitz, K et al. Drinking Risk Level Reductions Associated with Improvements in Physical Health and Quality of Life Among Individuals with Alcohol Use Disorder. Alcoholism: Clinical and Experimental Research 42(12):2453-2465, 2018

2.   Krieter P, et al. Enhanced Intranasal Absorption of Naltrexone by Dodecyl Maltopyranoside: Implications for the Treatment of Opioid Overdose. Journal of Clinical Pharmacology, 2019 https://www.opiant.com/wp-content/uploads/2019/05/2019-IN-NTX-J-Clin-Pharm-1.pdf

3.   Research & Development Meeting on Emerging Therapeutics for the Treatment of Addiction and Drug Overdose. Available at: http://ir.opiant.com/events/event-details/research-development-meeting-emerging-therapeutics-treatment-addiction-and

4.   Carvalho AF, Heilig M, Perez A, Probst C, Rehm J. Alcohol use disorders. Lancet. 2019 Aug 31;394(10200):781-792. doi: 10.1016/S0140-6736(19)31775-1. PMID: 31478502.

5.   Weerts E, Kim Y, Wand G, et al. Differences in δ and μ opioid receptor blockade measured by positron emission tomography in naltrexone-treated recently abstinent alcohol-dependent subjects. Neuropsychopharm. 2008;33:653-665.

6.   National Institute on Alcohol Abuse and Alcoholism. Available at: https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/alcohol-use-disorders

7.   World Health Organization. Available at: https://www.who.int/health-topics/alcohol#tab=tab_1

8.   Spencer, M et al. Rates of Alcohol-induced Deaths Among Adults Aged 25 and Over in Urban and Rural Areas: United States, 2000–2018, NCHS Data Brief No. 383, October 2020

9.   Pollard, M et al. Changes in Adult Alcohol Use and Consequences During the COVID-19 Pandemic in the US. Jama Network doi: 10.1001/jamanetworkopen.2020.22942, Sept 2020