January 22, 2025 

– Study achieved primary endpoint of statistically significant reduction in pain intensity compared to placebo following abdominoplasty surgery –

– Strong results of 1.34 mean hourly difference from placebo in NRS scale demonstrate cebranopadol’s potential as an effective treatment option for moderate-to-severe acute pain –

– Study demonstrated a favorable safety and tolerability profile comparable to placebo indicating cebranopadol’s potential to be a highly effective treatment option for moderate-to-severe acute pain –

MONMOUTH JUNCTION, NJ, January 22, 2025 – Business Wire – Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company, today announced positive topline results from its ALLEVIATE-1 pivotal Phase 3 clinical trial evaluating cebranopadol, an investigational therapy, for the treatment of moderate-to-severe acute pain in patients following abdominoplasty surgery. These results add to the growing body of data underscoring the promising efficacy and safety profile of cebranopadol, a first-in-class pain therapy involving dual-nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonism. This dual-NMR agonist has the potential to deliver significant pain relief comparable to opioids with minimized risk of significant side effects, dependence and addiction by leveraging the body’s pain biology modulation processes, synergizing the analgesic and safety characteristics of the NOP receptor with the analgesic advantages of the MOP receptor.

The results of the clinical study demonstrated a statistically significant reduction in pain intensity as measured using the Pain Numeric Rating Scale (NRS) Area Under the Curve for the 44 hours following surgery (AUC4-48) as the primary endpoint. Specifically, treatment with cebranopadol 400 µg once per day for two days resulted in a statistically significant reduction in pain intensity compared to placebo (LS Mean difference [SE] of 59.2 [14.36]; p<0.001). Additionally, cebranopadol was generally well tolerated and exhibited a favorable safety profile that was comparable to placebo, with no serious adverse events related to cebranopadol. The most common adverse event was nausea.

“These are extremely encouraging results, emphasizing the important role cebranopadol could play in effectively and safely alleviating moderate-to-severe acute pain for patients,” said Harold Minkowitz, M.D., primary investigator in the ALLEVIATE-1 study and president of analgesics, perioperative & hospital-based research at Evolution Research Group. “Our team was impressed by the magnitude of analgesia seen, suggesting that cebranopadol’s novel mechanism of dual-NMR agonism has the potential to be as effective as opioids in the post-surgical setting. This analgesic efficacy, combined with evidence from prior clinical studies showing low drug likability and potential for fewer respiratory events, demonstrate that cebranopadol could help address a critical unmet medical need for the millions of people who experience acute pain.”

“We are excited by the results from the ALLEVIATE-1 trial demonstrating a strong level of pain relief,” said Ketan Mehta, founder and chief executive officer at Tris Pharma. “The opioid crisis has highlighted the urgent need for pain management options that treat moderate-to-severe pain as effectively as opioids but do not carry similar risk of addiction and detrimental side effects. We believe cebranopadol has the potential to transform the treatment landscape for patients suffering from acute pain.”

Tris plans to submit full results from the ALLEVIATE-1 abdominoplasty clinical trial for presentation at an upcoming medical congress. In Q1 2025, Tris also plans to share results evaluating cebranopadol in two additional studies, an intranasal human abuse potential study and ALLEVIATE-2, a Phase 3 clinical study in patients following bunionectomy, with an NDA submission expected later this year. Tris plans to conduct cebranopadol studies in multiple chronic pain indications beginning in the second half of 2025.

About ALLEVIATE-1
The ALLEVIATE-1 clinical trial (NCT06545097) is a Phase 3 multicenter, randomized, double-blind, placebo-controlled study. The primary objective of ALLEVIATE-1 is to evaluate the analgesic efficacy of cebranopadol compared with placebo for the management of moderate-to-severe acute pain following full abdominoplasty as measured by pain intensity (11-point numeric rating scale) assessments. Secondary objectives include assessing the analgesic efficacy of cebranopadol through use of rescue medication, early discontinuations and subject overall assessment of study medication.

About Cebranopadol (TRN-228)
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). These receptors are partially homologous to each other, and they play both complementary and distinct roles to modulate pain biology pathways. Studied in over 32 clinical trials in over 2,200 patients, cebranopadol’s profile has been well-characterized in pain management studies. It has demonstrated 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 could become the first dual-NMR pain-relief therapy with the demonstrated ability to provide efficacy equivalent to opioids with less potential for misuse or risk of physical dependence, addiction or overdose.

Cebranopadol’s novel mechanism of action has potential in treating patients with substance use disorders. Tris plans to continue to evaluate cebranopadol’s potential to help patients break the cycle of opioid addiction. 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.

About Tris Pharma
Tris Pharma is a privately held, innovation-driven biopharmaceutical company that is applying its drug development capabilities and proprietary technologies to transform the treatment of ADHD, pain, addiction and disorders of the central nervous system. Tris is an established commercial organization with a robust portfolio of best-in-class ADHD products and a promising pipeline of differentiated, near-term drug candidates. More information is available at www.trispharma.com and on LinkedIn @TrisPharma.