Adneuris Therapeutics Reaches Key Regulatory Milestone with FDA Submission of New Drug Application for Cebranopadol in Moderate-to-Severe Acute Pain

If approved, cebranopadol would be the first dual NOP/MOP receptor (dual-NMR) agonist analgesic available for moderate-to-severe acute pain, introducing a novel mechanism of action to a treatment landscape in need of additional therapeutic options

NDA submission is backed by positive results from the pivotal Phase 3 ALLEVIATE-1 and ALLEVIATE-2 studies, which met their primary efficacy endpoints and demonstrated cebranopadol’s potential to significantly reduce moderate-to-severe acute pain across two surgical pain models

Application includes a comprehensive human abuse potential assessment with findings suggesting cebranopadol may offer a significantly lower and differentiated abuse potential profile in a head-to-head comparison with Schedule II and Schedule IV pain drugs, reinforcing its potential as a novel approach to acute pain management

MONMOUTH JUNCTION, N.J., Nov. 09, 2026 (GLOBE NEWSWIRE) -- Adneuris Therapeutics, a wholly owned subsidiary of Tris Pharma advancing a novel approach to pain management, today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for cebranopadol for the treatment of moderate-to-severe acute pain in adults. Cebranopadol is an investigational, first-in-class dual nociceptin/orphanin FQ peptide (NOP) and mu-opioid peptide (MOP) receptor (dual-NMR) agonist analgesic.

“The submission of this NDA is a significant milestone for the pain community,” said Charles Argoff, M.D., Professor and Vice Chair of Neurology and Director of the Comprehensive Pain Management Center at Albany Medical College, and Past President of the American Academy of Pain Medicine (AAPM). “In the wake of the opioid crisis, clinicians treating acute pain have too often had to choose between meaningful relief and the well-documented risks these pain treatments offer. Patients and clinicians deserve more choices. Cebranopadol’s dual NOP/MOP mechanism of action offers a novel approach with the potential to expand treatment options for clinicians and patients and help reshape how moderate-to-severe acute pain is managed.”

The NDA is supported by two pivotal Phase 3 studies, ALLEVIATE-1 (NCT06545097) and ALLEVIATE-2 (NCT06423703), which evaluated cebranopadol across two different surgical pain models, respectively. In both studies, cebranopadol 400 µg met the primary efficacy endpoint, producing significant reductions in pain intensity versus placebo after abdominoplasty (LS mean difference -59.2; p<0.001) and bunionectomy (LS mean difference -56.1; p<0.001). Patients treated with cebranopadol also used significantly less rescue medication than those who received placebo (p<0.001), and cebranopadol was well tolerated, with no drug-related serious adverse events reported. The most common adverse events (≥10%) reported across both Phase 3 studies included nausea, vomiting, and dizziness.

“Effective control of acute postoperative pain remains a significant clinical challenge, and trying to ‘push through the pain’ can have lasting consequences,” said Steven P. Cohen, M.D., Vice Chair of Pain Medicine at Northwestern University Feinberg School of Medicine and a retired Army colonel. “When acute pain is undertreated, it can become chronic, affecting patients long after the initial injury or surgery. The ALLEVIATE program demonstrated significant reductions in pain intensity versus placebo across both validated pain models. If approved, cebranopadol could offer clinicians a novel mechanism of action for treating moderate-to-severe acute pain, representing a potentially meaningful advancement in the treatment landscape by providing an additional option to manage pain before it becomes more difficult to control.”

The submission also includes a comprehensive abuse potential assessment drawing on behavioral pharmacology studies, human abuse potential studies, and an analysis of abuse- and withdrawal-related adverse events across the clinical program. In recreational opioid users, in a head-to-head comparative study, cebranopadol at doses up to 2.5 times the anticipated maximum therapeutic dose showed significantly lower abuse potential than the Schedule II opioid, oxycodone, and the Schedule IV opioid, tramadol. In separate studies that are part of this submission, the withdrawal-related adverse events after abrupt discontinuation or stopping treatment quickly were rarely reported in studies of up to 14 weeks. Preclinical studies suggested that cebranopadol was significantly less likely to encourage repeated drug-seeking behavior compared with opioids that act primarily on the mu-opioid receptor (MOP).

“Roughly 120 million opioid prescriptions are still written each year in the United States,¹ which shows how much we continue to rely on medications with well-known risks of misuse,” said Mark Greenwald, Ph.D., Director of the Substance Addiction Research Division at Wayne State University. “That’s why human abuse potential data are so important when evaluating new options for the pain community. In head-to-head studies, cebranopadol showed lower abuse potential than oxycodone and tramadol. That’s consistent with the understanding that NOP receptor activity modulates the effects of MOP agonism, and it’s a profile that warrants further attention as we look to advance acute pain treatments that provide meaningful analgesia while potentially addressing some of the abuse-related concerns associated with opioids.”

“Advances in our understanding of how the NOP and MOP receptors work together have opened new avenues in pain research,” said Jim Potenziano, Chief Science and Development Officer, Adneuris Therapeutics. “Our R&D teams have spent a number of years investigating the science and cebranopadol reflects the depth and persistence of that work. Submitting the NDA is an important milestone, and we are grateful to the patients who participated in our trials, the advocacy organizations that partnered with us, and the broader pain community and physician experts whose perspectives have helped guide our research. We look forward to the FDA’s review of our application and to the possibility of bringing an innovative treatment option to people living with moderate-to-severe acute pain.”

Following the submission, the FDA will review the application to determine whether it is complete and acceptable for filing. Adneuris expects to hear from the FDA regarding acceptance within approximately 60 days of submission. Upon acceptance, the FDA will assign a review designation and a Prescription Drug User Fee Act (PDUFA) date.

About Adneuris Therapeutics 
Adneuris Therapeutics, a wholly owned subsidiary of Tris Pharma, is dedicated to developing new therapies for people living with pain. Guided by a patient-first approach, the company is focused on advancing innovative science with the goal of improving pain management and addressing unmet patient needs. Adneuris is committed to helping shape the future of pain care through research, collaboration, and a focus on delivering meaningful treatment options. 

For more information, visit https://adneuris.com/. 

About Tris Pharma, Inc. 
Tris Pharma, Inc. is a privately held, innovation-driven biopharmaceutical commercial-stage company that is applying drug development capabilities and proprietary technologies to transform the treatment of ADHD, pain, and disorders of the central nervous system into advanced, targeted drug delivery. Tris markets a portfolio of best-in-class ADHD products and is developing a robust pipeline of differentiated near-term drug candidates. 

For more information, visit www.trispharma.com. 

About Cebranopadol 
Cebranopadol is a first-in-class investigational therapy that targets two key receptors, the nociceptin/orphanin FQ peptide (NOP) and µ-opioid peptide (MOP) receptors (a dual-NMR agonist), for the treatment of moderate-to-severe pain, as well as opioid use disorder (OUD). Studied in over 34 clinical trials in more than 2,400 participants, cebranopadol's profile has been well characterized in pain management studies, demonstrating positive clinical results in acute pain, chronic pain and diabetic neuropathic pain with a favorable safety profile. The FDA granted Fast Track Designation to cebranopadol for chronic low back pain, and if approved, it has the potential to become the first dual-NMR agonist to provide robust pain relief with a reduced risk of dependence, respiratory depression, or abuse potential than selective MOP agonists such as oxycodone. 

Cebranopadol's novel mechanism of action also has potential in treating patients with substance use disorders (SUDs). The National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), has awarded Tris a five-year grant of up to $16.6 million to study cebranopadol's potential to treat OUDs and SUDs. 

Contact: 
Cheryl Patnick 
Tris Pharma 
732-823-4940 

Media Contact: 
Madelin Hawtin 
LifeSci Communications 
MHawtin@lifescicomms.com  

1. Centers for Disease Control and Prevention (CDC). U.S. Opioid Dispensing Rate Maps. https://www.cdc.gov/overdose-prevention/data-research/facts-stats/us-dispensing-rate-maps.html