The world needs a new approach to treating serious pain

Cebranopadol is an investigational first-in-class analgesic in clinical development for the treatment of moderate-to-severe pain. Its novel mechanism has the potential to transform pain treatment so that patients can obtain relief with minimized risk of significant side effects. To date, cebranopadol has been studied in over 2,000 patients across 32 clinical trials and has demonstrated a promising efficacy and safety profile.

Cebranopadol’s novel mechanism of action targets two key receptors, the nociceptin/orphanin FQ peptide (NOP) and µ-opioid peptide (MOP) receptors. These receptors play complementary and distinct roles to modulate pain biology, synergizing the analgesic and safety characteristics of the NOP receptor with the analgesic advantages of the MOP receptor

The human body utilizes sophisticated pain modulation pathways with key receptors that receive and transmit pain signals. Two of these key receptors are the NOP and the MOP receptors, which have co-evolved to work together to regulate pain.

Current treatments for moderate-to-severe pain involving opioids have well-described safety problems that may largely derive from singularly targeting the MOP receptor. Activation of the NOP receptor has demonstrated distinct and complementary effects to MOP, resulting in less respiratory depression, less stimulation of the brain reward pathway and less euphoria (Ciccocioppo 2000; Di Giannuario 2000; Linz 2017). This coactivation of NOP and MOP receptors (“dual-NMR”) is the key to cebranopadol’s unique mechanism of action.

In clinical trials to date, cebranopadol has exhibited efficacy comparable to opioids and has the potential to address an unmet medical need for patients suffering from pain. With its novel, dual-NMR mechanism of action, cebranopadol offers the potential to effectively treat moderate-to-severe pain with minimized risk of significant side effects, especially dependence, addiction and respiratory depression.

Two cebranopadol human abuse potential studies conducted head-to head against Class-II and Class-IV opioids have demonstrated that cebranopadol-treated subjects, even at supratherapeutic doses, performed much better as measured by drug-liking. Moreover, data to date suggest that cebranopadol does not produce meaningful physical dependence. In studies of subjects treated with cebranopadol for up to 14 weeks, abrupt discontinuation of cebranopadol did not require tapering or cause patients to exhibit clinically relevant withdrawal symptoms.

Cebranopadol’s novel mechanism of action also lends promise in treating patients with substance use disorders. Tris plans to continue to evaluate cebranopadol to treat these patients and has been provided a $16.6 million grant by the National Institutes of Health (NIH) to study the drug for opioid use disorder.

Tris anticipates submitting an NDA for acute pain in 2025.

In Q1 2025, Tris shared positive results of its two registrational acute pain trials in patients following abdominoplasty and bunionectomy surgeries. These data are foundational to discussions with regulators in anticipation of NDA submission.

Tris anticipates conducting clinical trials in chronic pain conditions including neuropathic pain. Cebranopadol has been granted Fast Track Designation for chronic low back pain.