Pain is a common human experience, affecting millions of patients in the US. It significantly reduces quality of life, impacting our daily activities, productivity, and mental well-being.

Adneuris Therapeutics (a subsidiary of Tris Pharma), a US-based biopharmaceutical company, is developing a first-in-class analgesic with the potential to overcome the limitations of current pain treatment options and help to address the nation’s opioid epidemic. Adneuris believes its investigational therapy cebranopadol may represent a revolutionary new option for pain treatment with the potential for a reduced risk of abuse, addiction, and serious adverse effects associated with drugs like oxycodone.

News releases: Positive results in Phase 3 clinical trials with new pain therapy, cebranopadol

Tris Pharma showcases a novel mechanism of dual-NOP/MOP (NMR) agonism for the treatment of moderate-to-severe acute pain and encores positive Phase 3 data at 2025 Annual PAINWeek meeting in Las Vegas in BusinessWire

Investigational pain therapy cebranopadol succeeds in second Phase III clinical trial in Applied Clinical Trials 

Study results validate a fundamentally new approach to treating pain.

With over 2,400 participants enrolled across clinical programs, we have generated robust evidence demonstrating cebranopadol’s potential as a treatment option that prioritizes both efficacy and safety, directly addressing the need for effective pain relief with reduced risk of the side effects associated with treatments such as oxycodone.^1-5

Cebranopadol has been rigorously evaluated in two pivotal Phase 3 trials: ALLEVIATE-1 (abdominoplasty, also know as a “tummy tuck”) and ALLEVIATE-2 (bunionectomy, also known as bunion surgery”), assessing efficacy in moderate-to-severe pain following soft and hard tissue surgical procedures. In both studies, cebranopadol showed a significant reduction in pain (compared to placebo) over 48 hours, reduction in opioid rescue medication use (compared to placebo), sustained pain control indicted by longer time to first rescue dose, and an efficacy comparable to standard-of-care therapies with a differentiated safety profile.

In clinical trials across various pain types, cebranopadol has shown a favorable safety profile. 

In clinical trials, Adneuris’s novel analgesic, cebranopadol, was generally well tolerated, with nausea being the most frequently reported adverse event. Abuse potential studies in both oral and intranasal (via the nose) administration demonstrated that cebranopadol has a lower risk of misuse compared to Schedule II and IV comparators, such as oxycodone and tramadol. Drugs like oxycodone that only target MOP receptors showed a causal link to physical dependence and had to be stopped gradually over time to minimize withdrawal symptoms. In contrast, study participants taking cebranopadol where able to simply stop taking the medication at the end of each trial without problems – even when involved in trials that administered doses above those recommended for pain. 

References: 

1. Pacifico S, Albanese V, Illuminati D, Marzola E, Fabbri M, Ferrari F, Holanda VAD, Sturaro C, Malfacini D, Ruzza C, Trapella C, Preti D, Lo Cascio E, Arcovito A, Della Longa S, Marangoni M, Fattori D, Nassini R, Calò G, Guerrini R. Novel Mixed NOP/Opioid Receptor Peptide Agonists. J Med Chem. 2021 May 27;64(10):6656-6669.
2. Singla N, Minkowitz H, Vaughn B, Grieco J, Lesnick M, Hackworth J. Results of a Randomized, Placebo-Controlled, Phase 3 Trial of Cebranopadol for the Treatment of Acute Pain After Abdominoplasty. Presented at: American Society of Regional Anesthesia (ASRA); May 2025
3. Apseloff G, Pardo A, Shram M, Grieco JC, Lesnick ML, Hackworth JC. Limited Oral Abuse Potential of Cebranopadol, a Novel Potent Analgesic, Compared to Tramadol and Oxycodone in Recreational Opioid Users. Presented at: PainWeek; September 2023
4. Shram M, Apseloff G, Grieco J, Fam D, Lesnick M, Hackworth J. Abuse Potential Assessment of Cebranopadol, a Novel Dual Nociceptin (NOP) and Mu Opioid (MOP) Receptor (NMR) Agonist: Implications for Scheduling. Presented at: The College on Problems of Drug Dependence; June 2025.
5. Fam D, Pardo A, Hackworth J. Cebranopadol, a Novel Potent Analgesic: Pooled Analysis of Clinical Opiate Withdrawal Scales. Presented at: PainWeek; September 2022.