The U.S. remains firmly in the grip of a progressive opioid crisis of addiction and overdose. In 2019 nearly 50,000 people died of an opioid overdose and an estimated 3 million people have Opioid Use Disorder (OUD). Libero Pharma’s program to develop a naltrexone transdermal patch will address multiple HEAL objectives by providing new prevention and treatment alternatives, optimizing current medication-assisted therapy, and improving access to treatment. The antagonist naltrexone is one of only three medications with proven benefit in OUD relapse prevention. With poor tolerance and compliance in oral form, intramuscular (IM) naltrexone is the only viable antagonist option in the OUD population. Despite being approved in 2010, it is prescribed to fewer than 30,000 patients in the U.S. annually. Patient uptake is limited by availability, mode of administration (nurse- administered 4mL deep gluteal injection), cost, and low adherence. Libero has assembled a highly experienced team to bring to market a novel naltrexone transdermal patch (NNTP), which shares the benefits of IM naltrexone in that it is non-addictive and avoids first-pass metabolism and the resultant intolerance. As well as an easy-to-use alternative in OUD relapse prevention, NNTP also offers an accessible and undaunting option both for stable patients looking to take the final step away from chronic agonist use, and off-drug patients struggling with cravings at risk of relapse. The NNTP would eliminate the administrative burden, patient discomfort, and cost barriers that currently limit the use of IM naltrexone. This presents a genuine opportunity for widespread NNTP use in primary care where a vast and growing opioid-dependent population urgently requires care. This programme has been informed by clear input from the FDA, both in terms of plasma naltrexone level requirements and the required regulatory steps. Libero will pursue a 505(b)(2) pathway to bring NNTP to market for OUD relapse prevention. The UG3 Phase will include IND-enabling activities to secure an FDA issuance of an IND. The UH3 Phase will evaluate efficacy and safety of the NNTP in a multi-site, double- blind, randomized controlled trial against the IM naltrexone comparator over 6 months.

The overall goal of this project is to develop a novel, highly effective, transdermal patch to deliver naltrexone to prevent relapse in patients with opioid use disorder. If successful, this new formulation will provide physicians and patients with an accessible, low-cost, reversible, and well-tolerated method of delivering naltrexone. Project Narrative Page 1