STSS Aspire Heal Task Order 10

在美国，每天有超过2500万人经历疼痛（2012年全国健康访谈调查数据），需要安全、无成瘾的治疗来减轻他们的痛苦。这种临床需求非常重要，因为治疗急性和慢性疼痛的阿片类药物的过度处方和滥用助长了目前阿片类药物使用障碍和过量死亡的流行，阿片类药物用于长期疼痛管理的有效性受到质疑。安全、有效和不成瘾性的药物（小分子和生物制剂）治疗疼痛、减轻成瘾和逆转药物过量是解决阿片类药物危机的关键，这种危机在COVID-19大流行后只会恶化。鉴于先前药物开发工作的失败和局限性，需要识别新靶点，具有新结构，并且可以在基于人的生理相关的体外系统中识别的药物。

Over 25 million people in the United States experience pain every day (2012 National Health Interview Survey data) and need safe, addiction-free treatments to alleviate their suffering. This clinical demand is of tremendous importance given that overprescribing and abuse of opioids for managing acute and chronic pain has fueled the current epidemic of opioid use disorder and overdose deaths, and the effectiveness of opioids for long-term pain management is being questioned. Safe, effective, and non-addictive drugs (small molecules and biologics) to treat pain, mitigate addiction and reverse overdose are key to addressing the opioid crisis that has only worsened following the COVID-19 pandemics. Given failures and limitations of previous drug development efforts, drugs that recognize novel targets, have novel structures, and can be identified in human-based, physiologically relevant in vitro systems are needed. In 2018 NCATS by releasing NCATS ASPIRE Design Challenges, which solicited design ideas from the broader scientific community to address areas of the preclinical drug discovery process related to non-addictive pain treatment that could be accelerated by the introduction of new technologies related to: • Integrated Chemistry Databases • Electronic Synthetic Chemistry Portals • Predictive Algorithms • Biological Assays • Integrated Solutions of the above aspects In 2020, NCATS followed up with the ASPIRE Reduction-to-Practice Challenge, in which extramural researchers and innovators formed collaborative teams to deliver fully functioning prototypes of a non-addictive analgesics drug discovery platform that incorporated all the challenge topics from the design challenges (Integrated Chemistry Databases, Electronic Synthetic Chemistry Portals, Predictive Algorithms, Biological Assays). The Purdue University Team (PI: Gaurav Chopra) and the CiBots, Inc. Team (PI: Babak Esmaeli-Azad) garnered the grand prize and the runner-up prizes, respectively. We are now seeking to harness the array of technologies developed during the 2020 NCATS ASPIRE Reduction-to-Practice Challenge to build a non-traditional, merged, “super-team” of all expertise necessary to (1) complete integration of the two complementary platforms and (2) enhance the unified platform’s capability and rapidly deliver new analgesics drug candidates with safe and improved properties.