Development of Novel Topical Therapeutics for Psoriasis

牛皮癣新型局部治疗药物的开发

• 批准号: 10698601
• 负责人: Nuria Tubau Juni
• 金额: $ 29.59万
• 依托单位: BIOTHERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-05 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10698601
• 关键词: Acceleration; Address; Adrenal Cortex Hormones; Area; Atopic Dermatitis; Autoimmune Diseases; Biological Assay; Biological Markers; Biological Products; Biological Response Modifier Therapy; Biotechnology; Blood specimen; Cell Proliferation; Cells; Clinical; Combined Modality Therapy; Computer Models; Development; Disease; Disease remission; Dose; Flow Cytometry; Formulation; Foundations; Generations; Genus Hippocampus; Goals; High Pressure Liquid Chromatography; Histologic; Human; IL17 gene; IL18 gene; Immune; Immunophenotyping; In Vitro; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Interferon Type II; Lead; Lesion; Marketing; Metabolic; Metabolism; Modeling; Molecular; Oral; Outcome; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phase; Precision Health; Production; Proliferating; Property; Psoriasis; Rosacea; Safety; Serum; Signal Transduction; Skin; Skin Tissue; Small Business Innovation Research Grant; T-Lymphocyte; TNF gene; Technology; Testing; Therapeutic; Toxicology; Treatment Efficacy; United States; chemokine; commercial application; cytokine; effective therapy; efficacy evaluation; in vivo; inhibitor; keratinocyte; mouse model; novel; novel therapeutics; pharmacologic; precision medicine; prototype; public health relevance; research clinical testing; response; side effect; skin disorder; small molecule; translational potential

Development of Novel Topical Therapeutics for Psoriasis BioTherapeutics Inc (BTI) is an emerging biotech company that synergistically combines the power of advanced computational modeling with translational experimentation to accelerate the development of novel product candidates for precision medicine and health. An unmet clinical need for safer, more effective drugs for psoriasis remains as current therapies have limited efficacy and adverse side effects. Psoriasis afflicts over 7 million people in the United States and 15 million worldwide. Current therapies for psoriasis have limited long-term efficacy but significant adverse side effects. Three-fourths of psoriasis patients are managed with topical therapies, yet many of these therapies remain corticosteroids, which struggle to offer sustained remission and have been implicated in decrease responsiveness to treatment in a variety of autoimmune diseases. Meanwhile, roughly half of patients on oral or systemic psoriasis treatments will discontinue therapy due to loss of response or concern over side effects. Therefore, there is an unmet clinical need for the development of more effective, safer, topical therapeutics for the treatment of psoriasis. This SBIR Phase I application aims to develop a topical, first-in-class therapeutic for the treatment of psoriasis through a novel mechanism of action at the crosstalk between keratinocytes and immune cells. The Specific Aims for the SBIR Phase I application are to: (1) Characterize the therapeutic efficacy of our new therapeutic in a mouse model of psoriasis to determine the effects on keratinocytes and immune cells through histological, metabolic and flow cytometry analysis. (2) Develop a topical drug product formulation through generation of five or more prototype formulations and testing permeation in vitro and therapeutic efficacy in a mouse model of psoriasis. (3) Evaluate the translational efficacy in human primary cells from psoriasis patients through assessment of cytokine profile and functional assays. Expected successful outcomes: i) 50% reduction in composite score on day 7 with at least one dose of treatment in vivo, ii) >10% permeation by IVPT in our lead topical prototype, and iii) ≥ 40% decrease in IL-17 and IFNγ production in primary T cells treated with our novel therapeutic. The SBIR Phase II will perform IND-enabling safety and toxicology studies on the finalized topical formulation of our compund, characterize the efficacy of combination therapies of our topical new therapeutic with currently approved systemic agents for psoriasis, and initiate Phase 1b clinical testing in psoriasis patients. Commercial Application: This SBIR will develop a first-in-class topical therapeutic for psoriasis for addressing an unmet clinical need of 15 million patients, and a global market exceeding $12 billion annually.

牛皮癣新型局部治疗药物的开发 BioTherapeutics Inc (BTI) 是一家新兴的生物技术公司，协同结合了 先进的计算模型与转化实验，以加速新颖的开发 精准医疗和健康领域的候选产品对更安全、更有效的药物的临床需求尚未得到满足。 由于目前的治疗方法疗效有限且有不良副作用，因此牛皮癣仍然存在。 目前的治疗方法在美国有超过 700 万人受牛皮癣困扰，在全球有 1500 万人受牛皮癣困扰。 银屑病的长期疗效有限，但四分之三的银屑病患者有明显的副作用。 通过局部疗法进行治疗，但其中许多疗法仍然是皮质类固醇，很难提供 持续缓解，并与多种疾病的治疗反应性降低有关 与此同时，大约一半接受口服或全身性牛皮癣治疗的患者会出现自身免疫性疾病。 由于失去反应或担心副作用而停止治疗因此，临床上存在未满足的情况。 需要开发更有效、更安全的局部疗法来治疗牛皮癣。 I 期申请旨在开发一种局部、一流的治疗方法，通过 角质形成细胞和免疫细胞之间串扰的新作用机制。 SBIR 第一阶段申请的具体目标是： (1) 表征我们的新疗法在小鼠银屑病模型中的治疗效果，以确定 通过组织学、代谢和流式细胞术分析对角质形成细胞和免疫细胞的影响。 (2) 通过生成五个或更多原型制剂来开发外用药品制剂，并且 在银屑病小鼠模型中测试体外渗透性和治疗效果。 (3) 通过评估来自银屑病患者的人类原代细胞的转化功效 细胞因子谱和功能测定。 预期成功结果：i) 至少接受一剂治疗后，第 7 天综合评分降低 50% 体内，ii) 在我们的主要局部原型中通过 IVPT 渗透 >10%，以及 iii) IL-17 和 IFNγ 降低 ≥ 40% 用我们的新型疗法处理的原代 T 细胞中的产生。 SBIR 第二阶段将对最终的外用制剂进行 IND 支持的安全性和毒理学研究 我们的化合物，描述了我们的局部新疗法与目前的联合疗法的功效 批准治疗银屑病的全身药物，并在银屑病患者中启动 1b 期临床测试。 商业应用：该 SBIR 将开发一种一流的银屑病局部治疗药物，用于治疗银屑病。 满足 1500 万患者未满足的临床需求，以及每年超过 120 亿美元的全球市场。