Avoiding Adverse Opioid Outcomes with Proactive Precision Care

同品种STTR第一阶段赠款项目摘要 围手术期和处方阿片类药物通常会导致昂贵和不可预测的不良反应，包括生命 易受伤害患者的威胁性呼吸抑制和长期阿片类药物使用/误用。美国FDA警告 反对在术后缺氧性脑损伤和死亡的儿童中使用可待因和曲马多， 在哺乳期的母亲由于严重的呼吸问题和婴儿死亡。有一个紧急和未满足的关键 需要主动风险识别和个性化精确镇痛，以提高安全性和有效性 易受伤害人群中的阿片类药物。前瞻性精准医疗，包括术前基因分型和 基于科学证据的个性化镇痛;监管警告; CPIC指南;成本效益 建立基因分型的保险范围可以最大限度地减少过量使用阿片类药物和与 当前的试验和错误反应性药物。使用一种受专利保护的创新多基因组合 药物遗传学阿片类药物风险预测和决策算法，在本I期STTR应用中，OpalGenix，Inc. 建议验证哺乳母亲及其婴儿中阿片类药物不良后果的遗传特征， 剖腹产OpalGenix团队将与学术研究人员合作，并利用不重叠的NIH R 01资助（HD 089458和HD 096800），以补充此STTR申请，以实现以下两个目标： 1)研究并确定与成年女性术后阿片类药物不良反应相关的遗传风险因素 接受剖宫产和母乳喂养的新生儿，以及2）开发保险公司报销的多基因 实验室开发的测试（LDT）用于术前遗传风险预测和决策支持， 成人手术患者，以防止不良阿片类药物的结果。OpalGenix将开发最低可行产品 (MVP)，CLIA认证实验室中的一个精致的多基因面板，具有强大的组合药物遗传学 预测和决策支持，以在儿童中精确使用阿片类药物的个性化手术镇痛算法 和成年人。这有望防止常见的阿片类药物不良后果，如呕吐和罕见的生命 威胁和损害结果，如呼吸抑制，慢性持续性手术疼痛（CPSP）， 阿片类药物依赖和阿片类药物使用障碍（OUD）在脆弱的儿科和成人手术队列。未来 II期STTR将重点关注FDA对CLIA LDT的预批准，以识别遗传易感性 严重的阿片类药物不良结局，包括过量、OUD和新生儿阿片类药物戒断综合征 （NOWS）。根据目前阿片类药物的流行情况和预计2.15万亿美元的阿片类药物经济负担， 2020年和2040年，仅在美国，OpalGenix就有一个重要的商业市场，可以主动识别和 有效减少术后阿片类药物相关不良反应、CPSP、OUD、NOWS和过量， 最大限度地减轻数百万美国人的手术疼痛。

PROJECT SUMMARY FOR PREDICATE STTR PHASE I GRANT Perioperative and prescribed opioids often result in costly and unpredictable adverse effects, including life threatening respiratory depression and long-term opioid use/misuse in vulnerable patients. The US FDA warns against the use of codeine and tramadol in children due to postoperative anoxic brain injuries and deaths, and in nursing mothers due to serious breathing problems and infantile death. There is an urgent and unmet critical need for proactive risk identification and personalized precision analgesia to improve safety and effectiveness of opioids in vulnerable populations. Proactive precision medicine, including preoperative genotyping and personalized analgesia based on scientific evidence; regulatory warnings; CPIC guidelines; cost-effectiveness and established insurance coverage for genotyping could minimize excess opioid use and harm associated with the current trial and error, reactive medicine. Using a patent protected innovative multigene combinatorial pharmacogenetic opioid risk prediction and decision algorithm, in this Phase I STTR application, OpalGenix, Inc. proposes to validate the genetic signatures of adverse opioid outcomes in nursing mothers and their babies after cesarean deliveries. OpalGenix team will partner with academic researchers and leverage nonoverlapping NIH R01 funding (HD089458 and HD096800) to complement this STTR application to pursue the following two aims: 1) Validate and identify genetic risk factors associated with postoperative opioid adverse effects in adult women undergoing cesarean section and their breastfed neonates, and 2) Develop an insurer reimbursed multi-gene laboratory-developed test (LDT) for preoperative genetic risk prediction and decision support for pediatric and adult surgical patients to prevent adverse opioid outcomes. OpalGenix will develop a minimum viable product (MVP), a refined multi-gene panel in a CLIA certified laboratory with a robust combinatorial pharmacogenetic prediction and decision support to personalize surgical analgesia algorithm with precise opioid use in children and adults. This is expected to prevent common opioid adverse outcomes, such as vomiting and rare life threatening and compromising outcomes like respiratory depression, chronic persistent surgical pain (CPSP), opioid dependence, and opioid use disorder (OUD) in vulnerable pediatric and adult surgical cohorts. A future Phase II STTR will focus on the FDA pre-approval for a CLIA LDT to identify patients genetically pre-disposed to significant adverse opioid outcomes including overdose, OUD, and Neonatal Opioid Withdrawal Syndome (NOWS). Based on the current opioid epidemic and projected $2.15 trillion economic burden of opioids between 2020 and 2040 in the US alone, a significant commercial market exists for OpalGenix to proactively identify and effectively reduce postoperative opioid-related adverse effects, CPSP, OUD, NOWS, and overdose while maximizing surgical pain relief in millions of Americans each year.