Tris Pharma Initiates ALLEVIATE-1 and ALLEVIATE-2, Pivotal Phase 3 Trials Investigating Cebranopadol, a First-in-Class Compound with a Novel Mechanism of Action to Treat Pain

– Cebranopadol is a new investigational therapy that has demonstrated the potential to alter the treatment paradigm as the first dual-NMR agonist targeting both NOP and MOP receptors for a variety of pain types –

– Cebranopadol is a potential transformative therapy to regulate pain biology in a more balanced manner; potentially as effective as opioids to treat moderate-to-severe pain while having significantly less risk of abuse, physical dependence, addiction or overdose –

MONMOUTH JUNCTION, N.J.--(BUSINESS WIRE)--Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company focused on attention deficit hyperactivity disorder (ADHD), pain, addiction and neurological disorders, announced today the initiation of ALLEVIATE-1 and ALLEVIATE-2, pivotal Phase 3 trials evaluating the efficacy and safety of cebranopadol for the treatment of moderate-to-severe acute pain. Cebranopadol is a first-in-class investigational new therapy, with a novel mechanism of action that targets both the nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor, called dual-NMR agonist for the treatment of multiple types of pain.

“There is a monumental need to improve upon available treatments for the millions of individuals who suffer from pain each day and are unable to live a normal life,” said Ketan Mehta, founder and chief executive officer at Tris Pharma. “The initiation of our pivotal Phase 3 clinical trials for cebranopadol, a potentially transformational new pain therapy, is a significant step toward providing patients with a solution that is both highly effective and has a strong safety profile. We look forward to sharing the results from each study when they are available.”

The ALLEVIATE-1 and ALLEVIATE-2 clinical trials are registrational Phase 3 studies evaluating the efficacy of cebranopadol in patients undergoing abdominoplasty and bunionectomy, respectively. Together, the studies will enroll more than 500 patients at clinical trial sites in the United States. The results of these registrational studies will be part of the New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the approval of cebranopadol.

“Currently, physicians are constrained to prescribing pain medicines that either don’t effectively alleviate pain or do treat pain but often come with risk of significant side effects, misuse, addiction and overdose,” said Jeffrey Gudin, MD, professor of anesthesiology, perioperative medicine and pain management at the University of Miami Miller School of Medicine. “I’ve witnessed firsthand the transformative potential of this novel pain management therapy, and the initiation of these Phase 3 trials is an important step toward helping both physicians and their patients feel more confident in safely managing pain.”

If approved, cebranopadol will be the world’s first dual-NMR agonist. The investigational therapy is designed to leverage the body’s pain modulation processes, synergizing the analgesic and safety characteristics of the NOP receptor with the analgesic advantages of the MOP receptor to potentially deliver pain relief equivalent to opioids with minimized risk of significant side effects, dependence and potential addiction.

Cebranopadol’s profile has been well-characterized in more than 30 efficacy and safety clinical trials involving over 2,000 patients to date. Data from these studies suggest that cebranopadol is effective at reducing acute and chronic pain, including neuropathic pain, while reducing many of the harmful side effects seen in opioids and may have significantly lower risk of addiction and overdose.

About ALLEVIATE-1
The ALLEVIATE-1 clinical trial (NCT06545097) is a Phase 3 multicenter, randomized, double-blind, placebo-controlled study. Investigators at up to six clinical trial sites in the United States plan to enroll up to 300 patients. The primary objective of ALLEVIATE-1 is to evaluate the analgesic efficacy of cebranopadol compared with placebo for the management of moderate-to-severe 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 ALLEVIATE-2
The ALLEVIATE-2 clinical trial (NCT06423703) is a Phase 3 multicenter, randomized, double-blind, placebo- and active-controlled study. Investigators at up to eight clinical trial sites in the United States plan to enroll up to 240 patients. The primary objective of ALLEVIATE-2 is to evaluate the analgesic efficacy of cebranopadol compared with placebo for the management of moderate-to-severe pain following bunionectomy as measured by pain intensity (11-point numeric rating scale) assessments. Secondary objectives include assessing the analgesic efficacy of cebranopadol using rescue medication and evaluating the relative safety and tolerability of cebranopadol compared with oxycodone.

About Cebranopadol (TRN-228)
Cebranopadol is a first-in-class investigational therapy that targets both the nociceptin/orphanin FQ peptide (NOP) and µ-opioid peptide (MOP) receptors, called a dual-NMR agonist for the treatment of moderate-to-severe pain, as well as opioid use disorder (OUD). Cebranopadol offers a unique mechanism of action that takes advantage of the inherent properties of the NOP receptor, which has demonstrated both the potential to lessen the risk of misuse or addiction while still providing effective pain relief, and the potential to block drugs of abuse from producing drug-seeking behaviors. Studied in over 30 clinical trials in over two thousand 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 significantly favorable safety profile. The FDA granted Fast Track Designation to cebranopadol for chronic low back pain, and if approved, it could become the first and only pain-relief therapy with the demonstrated ability to provide efficacy equivalent to opioids with significantly less potential for misuse or risk of physical dependence, addiction or overdose.

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 and addiction and diseases of the central nervous system. Tris is an established commercial organization with a robust portfolio of best-in-class ADHD products with a promising pipeline of differentiated near-term drug candidates. More information is available at www.trispharma.com and on LinkedIn @TrisPharma.