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– Results shared at International Association for the Study of Pain (IASP) 2024 World Congress on Pain demonstrate that cebranopadol produces potent and prolonged pain relief with 25% less respiratory depression and significantly slower onset of effect with fewer respiratory adverse effects compared to oxycodone –

– Findings highlight therapeutic potential of cebranopadol, an investigational treatment with a promising, new mechanism of action designed to fill treatment gaps as a novel alternative to opioids for moderate-to-severe pain –

MONMOUTH JUNCTION, NJ, August 6, 2024 – Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company focused on attention deficit hyperactivity disorder (ADHD), pain, addiction and neurological disorders, today announced new clinical data demonstrating that cebranopadol, a dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonist, produces significantly less respiratory depression than oxycodone. The findings will be highlighted in a poster session on August 7, 2024, at the International Association for the Study of Pain (IASP) 2024 World Congress on Pain in Amsterdam.

“The study findings that will be shared at IASP 2024 offer clinically meaningful evidence that cebranopadol can provide effective and equal pain management with reduced potential of respiratory depression as compared to oxycodone,” said James Hackworth, Ph.D., president, brand division at Tris Pharma. “As a first-in-class, dual-NMR agonist in development to treat moderate-to-severe pain, cebranopadol has the potential to significantly reduce side effects associated with MOP-related agonism while simultaneously lessening MOP-related abuse potential and dependence. These new respiratory data add to the growing body of evidence that supports cebranopadol’s potential as a safer alternative to opioids, and we plan to initiate Phase 3 studies very soon.”

Mediated by activation of the MOP receptor, respiratory depression is a life-threatening complication that can occur following opioid administration. The clinical study being presented at IASP compared cebranopadol to oxycodone at supratherapeutic doses (i.e., doses that are greater than the therapeutic concentration). The trial specifically evaluated both cebranopadol’s and oxycodone’s impact on respiratory depression, ability to produce analgesia, the potential presence of a ceiling effect for cebranopadol at higher doses, and the evaluation of significant respiratory depression using a model for testing ventilatory response to hypercapnia. In the double-blind, placebo-controlled study, investigators randomized 30 healthy volunteers over a four-week treatment period to receive cebranopadol, oxycodone or placebo.

Summary of Key Findings Presented at IASP 2024
Findings shared in the IASP 2024 poster presentation titled “Cebranopadol effects on ventilatory drive, central nervous system, and pain,” demonstrate that NOP receptor activation with cebranopadol effectively attenuates respiratory depression and that its dual-NMR agonism produces potent, long-lasting analgesia. Key study results include:

• At equianalgesic doses, cebranopadol produces 25% less respiratory depression compared to oxycodone.
• Treatment with cebranopadol presents a longer time to impact on respiratory parameters compared to oxycodone, allowing for the gradual accumulation of arterial CO2 and mitigating the full manifestation of respiratory depression.
• Cebranopadol achieved prolonged analgesic effects with gradual onset and offset.
• Despite having a longer duration of effect, cebranopadol produces fewer respiratory adverse events over 24 hours, including apnea, respiratory depression and oxygen saturation decrease, compared to oxycodone.

“The delayed onset of respiratory effects as evidenced in this study highlights the differentiating characteristic of cebranopadol to significantly reduce MOP-related side effects frequently experienced with opioids,” said study author Albert Dahan, M.D., professor of anesthesiology, Leiden University Medical Center, Leiden, The Netherlands. “These results reinforce the safety profile of cebranopadol by demonstrating that it gives the body time to adjust its breathing, which in turn may aid in delivering both a safe and effective pain management solution to patients. Combined with data from previous clinical and preclinical studies of cebranopadol, these findings also suggest a ceiling of respiratory depression may exist in humans and bring us closer to offering a better therapeutic for acute and chronic pain.”

About Cebranopadol (TRN-228)
Cebranopadol is an investigational, first-in-class dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonist for the treatment of moderate-to-severe pain, as well as opioid use disorder (OUD). Cebranopadol offers a compelling and 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 while still providing effective pain relief, and the potential to block drugs of abuse from producing drug-seeking behaviors. The FDA granted Fast Track Designation to cebranopadol for chronic low back pain. Cebranopadol’s profile has been well-characterized in pain management studies, 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 neurological disorders, including addiction and diseases 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.

Company Contact
Cheryl Patnick
Tris Pharma, Inc.
cpatnick@trispharma.com

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Sam Brown, Inc.
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