Cebranopadol hemicitrate

– Study met primary endpoint demonstrating cebranopadol is significantly less likely to be misused intranasally (snorting) than oxycodone with majority of recreational opioid users indicating no desire to take cebranopadol again – – Results are similar to previously announced human abusability data from oral administration of cebranopadol compared to oxycodone (Schedule II) and tramadol (Schedule IV) – – Together these studies suggest that cebranopadol may have a significantly lower risk of abuse – MONMOUTH JUNCTION, NJ, USA I June 12, 2025 I Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company, today announced that the company will present intranasal human abusability datafrom cebranopadol, an investigational first-in-class oral dual NOP/MOP (dual-NMR) agonist, at the College on Problems of Drug Dependence (CPDD) Annual Meeting, taking place June 14-18, 2025, in New Orleans. The data will be presented in a late-breaking oral session and a poster presentation which highlight the significantly lower abuse potential of cebranopadol compared to established opioids such as oxycodone (Schedule II) and tramadol (Schedule IV). The late-breaking oral session will highlight positive results from an intranasal human abuse potential study demonstrating that snorting cebranopadol was significantly less liked compared to oxycodone. These results expand on an earlier study that demonstrated cebranopadol has significantly less oral abuse potential than oxycodone (Schedule II) and tramadol (Schedule IV). The poster presentation summarizes all key data to date that characterize the low abuse potential of cebranopadol. Overall, these studies support the novel mechanism of action of cebranopadol, where NOP receptor activation minimizes the potential abusability associated with MOP receptor agonists. “These results demonstrate the potential of cebranopadol, and likely other dual-NMR agonists, to change how we treat pain while reducing the risk of misuse,” said Ketan Mehta, founder and CEO at Tris Pharma. “We continue to believe in the promise of cebranopadol to transform the lives of patients with moderate-to-severe pain as evidenced by data that show strong efficacy as well as significantly lower abusability than existing options.” “The dangerous practice of crushing and insufflating opioids, often a progression from recreational use and a precursor to the use of more potent substances, underscores the critical need for analgesic alternatives with reduced potential for misuse,” said Megan Shram, Ph.D., an expert on human abuse potential studies. “This research indicates that cebranopadol exhibits a distinct pharmacological profile compared to conventional opioids such as oxycodone, and neither the oral nor intranasal administration of cebranopadol has demonstrated the capacity to produce reinforcing (i.e., euphoric) effects typically observed with high abuse liability opioids. These findings suggest that the treatment of pain with cebranopadol may offer an improved public health safety profile and more favorable risk-benefit ratio compared to traditional opioid analgesics.” Tris Pharma Presentations Poster Presentation Late-Breaking Oral Session Grant Funding Research reported in this press release was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number UG3DA059285. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. About Acute Pain Acute pain affects millions of patients each year and is caused by injury, surgery, illness, trauma, burns or painful medical procedures, which can last up to three months, and typically resolves once the underlying cause is treated or healed. Moderate-to-severe acute pain can often only be effectively treated with conventional opioid analgesics such as oxycodone, especially following joint replacements and other orthopedic procedures, invasive surgeries, and major traumas and burns. 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 33 clinical trials in more than 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 similar to conventional 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 (SUDs). 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 markets a portfolio of best-in-class ADHD products and is developing a promising pipeline of differentiated, near-term drug candidates. More information is available at www.trispharma.com and on LinkedIn @ TrisPharma . SOURCE: Tris Pharma

▎药明康德内容团队编辑 Tris Pharma今日宣布，在研疗法cebranopadol，在治疗拇囊炎切除术后中度至重度急性疼痛的关键性3期临床试验ALLEVIATE-2中达到主要临床终点，与安慰剂相比显著减轻患者疼痛。此前，cebranopadol在治疗腹壁整形手术后中度至重度急性疼痛的3期临床试验ALLEVIATE-1中也达到试验主要终点。基于这些积极结果，该公司计划今年向美国FDA递交新药申请（NDA）。 试验数据显示，ALLEVIATE-2临床研究达到了主要终点，即在给药后2小时至48小时内，使用疼痛数字评分量表（NRS）计算曲线下面积（AUC2-48）为指标，显示疼痛强度有统计学上显著的降低。具体而言，每日口服cebranopadol（400 µg）治疗组与安慰剂组相比，疼痛强度的最小二乘均值差为56.1（p<0.001）。研究中另一患者队列接受口服即释型阿片类镇痛药oxycodone治疗。活性对照组与安慰剂相比显示出更好的镇痛效果，但其平均镇痛效果低于cebranopadol。 ▲Cebranopadol在临床试验ALLEVIATE-2中与安慰剂相比显著降低患者疼痛（图片来源：参考资料[1]） 患者在镇痛不足时可使用额外镇痛选择，即补救治疗。试验结果显示，在为期7天的研究期间，接受cebranopadol治疗的患者中无需使用阿片类补救药物的比例显著高于接受安慰剂的患者（57.5%比28.4%；p<0.001）。此外，cebranopadol总体耐受性和安全性良好，未观察到严重不良事件，最常见的不良事件为恶心。 该公司表示，ALLEVIATE-1和ALLEVIATE-2临床研究结果，加上几项人体滥用潜力（HAP）研究中显示的强劲安全性数据，将提交给美国FDA，作为潜在批准的依据。Tris公司计划在即将召开的医学会议上报告ALLEVIATE-1和ALLEVIATE-2临床试验的完整结果。 Cebranopadol是一种潜在“first-in-class”的疼痛治疗药物，作用机制为伤害感受肽/孤啡肽FQ（NOP）受体和µ-阿片肽（MOP）受体双重激动剂。与阿片类药物相比，它有望在提供显著镇痛效果的同时，降低严重副作用、依赖性和成瘾风险。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料： [1] Tris Pharma Announces Positive Results from ALLEVIATE-2 Phase 3 Pivotal Trial for Cebranopadol, an Investigational First-in-Class Oral Dual-NMR Agonist, for the Treatment of Moderate-to-Severe Acute Pain. Retrieved March 6, 2025, from https://www.businesswire.com/news/home/20250306271136/en 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新