XVIR-110 an ultra-long-acting INSTI for HIV pre-exposure prophylaxis in IND-enabling studies

项目总结 虽然现在有针对艾滋病毒/艾滋病患者的成功的治疗方案和预防战略， 艾滋病毒大流行仍然是美国和世界范围内的一种公共卫生危机，有近4万名新感染者 每年仅在美国就有感染病例。为了防止艾滋病毒在脆弱人群中传播，美国预防性 服务工作组建议所有成年人和青少年接触前预防艾滋病毒(PrEP)，网址为 感染艾滋病毒的风险。尽管目前的抗逆转录病毒药物方案有效且耐受性良好，但使 终身抑制艾滋病毒-1感染和预防高危个人感染艾滋病毒-1， 合规率很低。长效抗逆转录病毒药物(ARV)有可能改善药物依从性， 减少病毒传播，防止新感染，限制病毒耐药性和系统性感染的出现 毒物。然而，使用长效抗逆转录病毒药物的关键挑战是延长给药间隔，以减少 医疗设施面临压力，每六个月一次的诊所就诊就会设立医疗设施。这一挑战很可能 降低合规性，特别是在PrEP设置中。有证据表明，依从性差会增加感染 发病率和产生抗药性的可能性。Exavir Treateutics，Inc.创造了一种超长- 通过开发一种超长效、纳米配方的可注射前药来发挥抗逆转录病毒作用，以克服这一挑战。 在我们第一阶段相当于数据的基础上，我们在这个直接到第二阶段SBIR项目中建议进一步开发 我们的药物通过1)完成药物物质的化学、制造和控制开发 药物产品，2)完成IND使能研究，以及3)获得FDA IND批准。完成后，这 直接转到第二阶段SBIR项目将使IND能够提交给FDA批准和准备 我们的第一阶段人类临床试验。如果成功，我们的新型“超”长效抗逆转录病毒病毒对HIV-1的影响 在现实世界中，已经感染艾滋病毒-1的个人的预防和生活质量将是深远的。

PROJECT SUMMARY While there are now successful treatment regimens and prevention strategies for people living with HIV/AIDS, the HIV pandemic remains a public health crisis in the United States and worldwide, with nearly 40,000 new infections each year in the US alone. To prevent the spread of HIV in vulnerable populations, the US Preventive Services Task Force has recommended HIV pre-exposure prophylaxis (PrEP) for all adults and adolescents at risk of HIV acquisition. Although current antiretroviral drug regimens are potent and well-tolerated, enabling the life-long suppression of HIV-1 infection and the prevention of HIV-1 infection in individuals at high risk, compliance rates are low. Long-acting antiretroviral drugs (ARVs) have the potential to improve drug adherence, reduce viral transmission, prevent new infections, and limit the emergence of viral drug resistance and systemic toxicities. However, the key challenge for using long-acting ARVs is to extend the dosing interval to reduce the pressure on the healthcare facilities, which are set up for every six-month clinic visits. This challenge likely reduces compliance, particularly in the PrEP setting. Poor compliance has been shown to increase infection rates and the possibility of developing drug resistance. Exavir Therapeutics, Inc has created an “ultra” long- acting ARV by developing an ultra-long-acting, nanoformulated injectable prodrug to overcome this challenge. Building upon our Phase I equivalent data, we proposed in this Direct-to-Phase II SBIR project to further develop our drug by 1) completing the Chemistry, Manufacturing, and Controls development of the drug substance and drug product, 2) completing IND-enabling studies, and 3) obtaining FDA IND approval. Upon completion, this Direct-to-Phase II SBIR project will enable the submission of an IND to the FDA for approval and preparation of our Phase I first-in-human clinical trial. If successful, the impact of our novel “ultra” long-acting ARV on HIV-1 prevention and quality of life for individuals already infected with HIV-1 will be far-reaching in real-world settings.