Developing a Novel Mixed Opioid Agonist for the Treatment of OUD

项目摘要 超过210万美国人患有阿片使用障碍(OUD)，每年导致4.7万人死亡。 寻求治疗的个人必须应对耻辱、有限的获得合格医疗专业人员的机会以及 获得药物辅助治疗(MAT)的官僚障碍，此外，还经常需要经历 垫前的戒断症状，所有这些加起来都是无效的进入系统。即使在接受治疗的时候， 患者面临着几个障碍，如疼痛、渴望、压力、羞耻、治疗不一致和复发 仍在接受有效的治疗方案。这只是实现长期目标所需的众多步骤之一。 节制和更稳定的生活。这条道路是痛苦的，对于这些人来说，可用的选择很少 个人和治疗他们的医务人员。 DMK建议使用DPI-125来扩展MAT的能力，使用小分子、三重(Mu、Delta和 Kappa)阿片受体激动剂。实验、临床和理论证据表明，DPI-125具有 在减少呼吸抑制(Delta激动症)方面的额外安全性和有效性优势 与目前可用的激动剂和拮抗剂治疗相比，亲和性降低(卡帕激动症)。 在这个项目中，我们的目标是证明DPI-125作为MAT试剂的可行性。我们打算这样做 通过确定DPI-125减轻阿片类药物戒断症状的最低剂量 吗啡依赖的啮齿动物模型。当前标准的护理药物将被用作主动药物 比较器。预计DPI-125将能够缓解戒断的生理症状， 潜在的剂量很低，而且起效快。这与其卓越的安全配置相结合(减少 呼吸抑制和滥用的可能性)将使它成为一个非常有价值的补充 兵工厂。DPI-125的疗效是否等于或优于美沙酮或丁丙诺啡，DMK Pharma将推动DPI-125的临床开发，以期改善患者状况 准入、依从性、耐受性和治疗进展。 鉴于DPI-125是临床阶段的资产，将其添加到OUD的垫子医疗设备中的潜力可能 在临床开发的短短几年内就会发生。

Project Summary Over 2.1 million Americans suffer from opioid use disorder (OUD) resulting in 47,000 deaths annually. Individuals seeking treatment must deal with stigma, limited access to qualified healthcare professionals and bureaucratic barriers to getting medication assisted treatment (MAT) and in addition often need to experience withdrawal symptoms prior to MAT which all add up to an ineffective system of access. Even on treatment, patients face several obstacles such as pain, craving, stress, shame, treatment inconsistency and relapse to be remain on an effective treatment regimen. This is just one of many steps needed towards long term abstinence and a more stable life. The path is harrowing, and there is a paucity of options available for these individuals and the medical staff who treat them. DMK proposes to expand MAT capabilities for OUD with DPI-125, with a small molecule, triple (mu, delta and kappa) opioid receptor agonist. Experimental, clinical and theoretical evidence suggests that DPI-125 has additional safety and efficacy advantages in terms of reduced respiratory depression (delta agonism) and reduced likability (kappa agonism) over currently available agonist and antagonist treatments. In this project, our objective is to demonstrate the feasibility of DPI-125 as a MAT agent. We intend to do this by identifying the lowest dose at which DPI-125 mitigates somatic signs of opioid withdrawal in a validated rodent model of morphine dependence. Current standard of care medications will be used as active comparators. It is anticipated that DPI-125 will be able to alleviate physiological symptoms of withdrawal, at potentially very low doses and with a rapid onset. This combined with its superior safety profile (reduced respiratory depression and abuse potential) would make it a highly valuable addition to the OUD armamentarium. Should efficacy of DPI-125 be equal or superior to that of methadone or buprenorphine, DMK Pharma will advance the clinical development of DPI-125 as a MAT for OUD with an intention to improve patient access, adherence, tolerance and treatment progress. Given that DPI-125 is a clinical stage asset, the potential of adding it to the MAT armamentarium for OUD could happen within just a few years of clinical development.