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

XVIR-110 是一种超长效 INSTI，用于 IND 支持研究中的 HIV 暴露前预防

基本信息

批准号：
10764186
负责人：
Brian Kearney
金额：
$ 105万
依托单位：
EXAVIR THERAPEUTICS INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-17 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10764186
关键词：
AIDS prevention Address Adolescent Adult Adverse reactions Anti-Retroviral Agents Biomedical Research CD4 Positive T Lymphocytes Canis familiaris Carbon Caring Chemistry Clinic Visits Clinical Research Clinical Trials Data Databases Development Documentation Dose Effectiveness FDA approved Fatty Acids Feedback Future Guidelines HIV HIV Infections HIV-1 HIV/AIDS Health care facility Human In Vitro Individual Infection Injectable Injections Kilogram Legal patent Lymphoid Macaca mulatta Macrophage Medicine Micronucleus Tests Mucous Membrane Mutation Oral Patients Persons Pharmaceutical Preparations Pharmacologic Substance Phase Phase I Clinical Trials Plasma Preparation Prevention Prevention strategy Process Prodrugs Program Development Proteins Public Health Quality of life Rattus Recommendation Regimen Research Institute Risk Rodent Site Small Business Innovation Research Grant Stearates Sterilization Surveys Suspensions Testing Therapeutic Toxicology Treatment Protocols United States United States Preventative Services Task Force Viral Viral Drug Resistance Vulnerable Populations Work analytical method drug development drug production drug resistance development first-in-human follow-up high risk improved in vivo infection rate manufacture manufacturing scale-up medication compliance men who have sex with men monocyte nano nanoformulation novel oral HIV pandemic disease pre-Investigational New Drug meeting pre-exposure prophylaxis preference pressure prevent stability testing success systemic toxicity transgender women trial design truvada uptake viral transmission

项目摘要

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.

项目摘要虽然现在有成功的治疗方案和预防策略，但针对艾滋病毒/艾滋病患者有艾滋病毒大流行仍然是美国和全球的公共卫生危机，近40,000个新的仅在美国，每年感染。为了防止艾滋病毒在弱势群体中的传播，美国预防性服务工作队建议对所有成年人和青少年的HIV预防前预防（PREP）获取艾滋病毒的风险。尽管当前的抗逆转录病毒药物方案具有潜力且耐受性良好，使得能够终身抑制HIV-1感染和预防高风险个体的HIV-1感染，合规率很低。长效抗逆转录病毒药物（ARV）具有改善药物依从性的潜力，减少病毒传播，防止新感染，并限制病毒耐药性和全身性的出现战术。但是，使用长效ARV的关键挑战是扩展剂量间隔以减少每六个月的诊所就诊就对医疗机构进行压力。这个挑战可能降低了合规性，尤其是在准备环境中。依从性差已显示出增加感染速率和产生耐药性的可能性。 Exavir Therapeutics，Inc创建了一个“超”长期通过开发超长作用，纳米构造的注射前药来克服这一挑战，从而作用ARV。在我们的I阶段等效数据的基础上，我们在此直接到相的II SBIR项目中提出了进一步发展我们的药物1）完成化学，制造和控制药物的开发药品，2）完成辅助研究，3）获得FDA IND批准。完成后，这个直接访问II SBIR项目将使IND提交FDA提交批准和准备我们的第一阶段人类临床试验。如果成功，我们的小说“超”长效ARV对HIV-1的影响在现实世界中，已经感染HIV-1的个体的预防和生活质量将是深远的。