Select Late-Stage CMC, Non-clinical Studies, and Quality Programs to Accelerate NRS-033 Towards Pivotal Studies and Registration in Opioid Use Disorder

PROJECT SUMMARY

The epidemic of opioid use disorder (OUD) is the greatest public health crisis the United States has faced in a

generation. Yet essentially the same three Food and Drug Administration (FDA) approved medications for OUD

(MOUD), in various formulations, have been available since the crisis began decades ago: opioid agonist

methadone, partial agonist buprenorphine and antagonist naltrexone. These few legacy defenses against the

staggering tide of addiction have proven feeble, primarily due to short treatment retention and lack of access.

These MOUD are poorly accepted, offered to 400%

longer duration of action than XR-NTX, corresponding to dramatically improved treatment retention. Given its

gradual decline and high trough levels of plasma nalmefene, NRS-033 should provide stronger and more

consistent opioid blockade, as well as a more forgiving dosing schedule than XR-NTX. Such upgrades are

critical for socially complex patients in today’s illicit market dominated by potent synthetic opioids, different from

that decades ago. Also, NRS-033 is a room temperature stable ready-to-use prefilled syringe, much easier to

use and clinically accessible than XR-NTX. Our proposed Aims seek to expedite NRS-033 into Phase 3 trials

and FDA registration, hence include: late stage (registration batch) chemistry, manufacturing, and controls

(CMC) for API and drug product, registration enabling non-clinical studies, quality systems, and regulatory

engagement with FDA. Despite significantly de-risked development, the timely advance of NRS-033 will have a

profound public health impact once available, reducing relapse and overdose risk for abstinence-seeking OUD

patients, helping defeat the prevailing stigma that opioid dependence is inescapable.