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

• 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
• 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

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 虽然现在对艾滋病毒/艾滋病感染者有成功的治疗方案和预防战略， 艾滋病毒的流行仍然是美国和全世界的一个公共卫生危机， 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 服务工作队建议所有成年人和青少年在 艾滋病毒感染的风险。虽然目前的抗逆转录病毒药物治疗方案是有效的和良好的耐受性，使 终身抑制HIV-1感染和预防高危人群HIV-1感染， 合规率较低。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，预防新的感染，并限制病毒耐药性和系统性感染的出现。 毒性然而，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 对医疗保健设施的压力，这些设施每六个月进行一次诊所访问。这一挑战可能 降低依从性，特别是在PrEP设置中。依从性差会增加感染 率和发展耐药性的可能性。Exavir Therapeutics，Inc创造了一种“超”长期- 通过开发一种超长效、纳米配方的可注射前药来克服这一挑战。 在我们的第一阶段等效数据的基础上，我们在这个直接到第二阶段的SBIR项目中建议进一步开发 通过1）完成原料药的化学、生产和控制开发， 药品，2）完成IND使能研究，3）获得FDA IND批准。完成后，这 直接进入II期SBIR项目将能够向FDA提交IND，以供批准和准备 我们的第一阶段人体临床试验如果成功，我们的新型“超”长效抗逆转录病毒药物对HIV-1的影响 预防和已经感染HIV-1的个人的生活质量将在现实世界中产生深远的影响。