Development of Novel Topical Therapeutics for Psoriasis

银屑病局部治疗新药物的研究进展 BioTherapeutics Inc（BTI）是一家新兴的生物技术公司，它协同结合了 先进的计算建模与平移实验，以加速开发新的 精准医疗和健康的候选产品。对更安全、更有效药物的未满足的临床需求 目前治疗牛皮癣的方法仍然疗效有限且副作用大。 银屑病在美国有超过700万人，在全世界有1500万人。的现行疗法 银屑病的长期疗效有限，但有显著的不良副作用。四分之三的牛皮癣患者 是通过局部治疗来管理的，但这些治疗中的许多仍然是皮质类固醇， 持续缓解，并与各种治疗反应性降低有关， 自身免疫性疾病与此同时，大约一半的口服或全身性银屑病治疗患者将 由于失去反应或担心副作用而停止治疗。因此，存在未满足的临床 需要开发用于治疗银屑病的更有效、更安全的局部治疗剂。该SBIR 第一阶段的申请旨在开发一种局部的，一流的治疗牛皮癣的治疗，通过一个 在角质形成细胞和免疫细胞之间的串扰的新的作用机制。 SBIR第一阶段申请的具体目标是： (1)在银屑病小鼠模型中表征我们的新疗法的治疗功效，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)通过生成五种或更多种原型制剂来开发局部制剂， 在银屑病小鼠模型中测试体外渗透和治疗功效。 (3)通过评估银屑病患者的人原代细胞中的 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% 在体内，ii）在我们的主要局部原型中IVPT渗透>10%，和iii）IL-17和IFNγ降低≥ 40% 在用我们的新治疗剂处理的原代T细胞中的产生。 SBIR II期将对最终的局部制剂进行IND启用安全性和毒理学研究 我们的化合物，表征我们的局部新的治疗与目前的联合治疗的疗效 批准用于银屑病的全身性药物，并启动银屑病患者的1b期临床试验。 商业应用：该SBIR将开发一流的银屑病局部治疗药物， 解决了1500万患者未得到满足的临床需求，全球市场每年超过120亿美元。

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.