FesariusTherapeutics Inc. I-Corps Program to Benefit the development and sales of its flagship product DermiSphere(tm)

™：一种先进的重建外科真皮再生支架 摘要 人体本身是不能再生真皮的。如果处理不当，大的全厚度 皮肤创伤(真皮的丧失)通过周围皮肤的收缩和疤痕的形成来愈合，这可能 最终导致慢性伤口形成、永久性损伤、残疾、毁容和病人痛苦。 多年来，自体组织移植(患者作为自己的捐赠者)一直是黄金标准 治疗这种类型的伤口，但缺乏外科专业知识，供区可用性差，且显著 供体部位的发病率严重限制了它的应用。在21世纪初，另一种“现成”的新真皮 形成疗法出现了，现在年销售额在5亿到10亿美元之间，增长了8%- 每年12%。按销售额计算的领先产品Integra™在治愈时间上存在缺陷，并且 在许多类型的全厚伤口场景中无效。DERMISPHERE™，它的建议产品 SBIR第一阶段的应用将是一种可植入的支架，可以快速恢复患者的功能性真皮。 获专利的三维显微图案化架构可引导细胞快速渗透 从伤口床进入支架基质，导致快速血管形成和新生真皮组织形成。 到目前为止，我们的小鼠研究表明，相对于 积分卡。我们的SBIR第一阶段建议和预期的第二阶段研究的集体长期目标是 准备进行临床试验的DermiSphere原型，可在避免皮肤的情况下触发快速皮肤再生 收缩和结疤。与目前可用的真皮替代品相比，DermiSphere将诱导 更快的伤口闭合，形成更多的功能组织，减少所需的程序，减少患者的痛苦 和实质性降低医疗保健成本。在这个第一阶段的研究中，我们将通过以下方式证明我们产品的可行性 完成以下具体目标：(1)通过测试其 当使用牛胶原蛋白配制时，通过放散方法进行体外潜在的细胞毒性。标准 成功：对皮球的生物学反应小于或等于轻微反应。(2)示范 皮球支持在体猪全层皮肤快速再生的能力 切除创面模型。成功标准：在研究的第21天，表皮使用75%的≥并创面 在研究第14天和第60天，收缩≤分别为20%和≤30%。我们的第二阶段研究将是一个全面的- 比例尺，全层切除猪伤口模型，以验证德米球的疗效优于INTERA。数据来自 这项研究还将用于改进规模化生产和临床前安全性的配方 药效测试要求。全面展示了DermiSphere优于Integra的功效 WIND模式目前是我们的第一个重大战略里程碑。达到这一里程碑将充分增加 FesariusTreateutics Inc.的股权价值，以吸引扩大运营规模所需的资本 制造、FDA提交和商业化。

DermiSphere™: An Advanced Dermal Regeneration Scaffold for Reconstructive Surgery ABSTRACT On its own, the human body is incapable of dermis regeneration. If not properly treated, large full-thickness skin wounds (loss of dermis) heal through contraction of surrounding skin and scar formation, which may ultimately lead to chronic wound formation, permanent damage, disability, disfigurement and patient suffering. For years, the autologous tissue transfer (a patient serving as their own donor) has been the gold-standard treatment for this type of wound, but lack of surgical expertise, poor donor site availability and significant donor-site morbidity severely limit its application. In the early 2000s, alternative, “off the shelf” neo-dermis formation treatments emerged, which now have annual sales between $500 million to $1 billion, growing 8- 12% annually. The leading product by sales, Integra™, possesses shortcomings in its time to heal and is ineffective in many types of full thickness wound scenarios. DermiSphere™, the proposed product of this SBIR Phase I application will be an implantable scaffold that rapidly restores patients’ functional dermis. DermiSphere’s patented three-dimensional microscopically patterned architecture guides rapid cell penetration from the wound bed into the scaffold matrix, leading to rapid vascularization and neo-dermal tissue formation. Our murine studies to date demonstrate DermiSphere’s superior invasion and neovascularization versus Integra. The collective long-term goal of our SBIR Phase I proposal and contemplated Phase II study is a DermiSphere prototype, ready for clinical trial, that triggers rapid dermal regeneration while avoiding skin contraction and scarring. When compared to currently available dermal substitutes, DermiSphere will induce faster wound closure, form more functional tissue, and lessen required procedures, reducing patient suffering and materially reducing health care cost. In this Phase I study we will prove the feasibility of our product by completing the following Specific Aims: (1) Demonstrate DermiSphere biocompatibility by testing its potential cytotoxicity in vitro by elution method, when formulated using bovine collagen. Criteria for Success: Biological response to DermiSphere is less than or equal to slight reactivity. (2) Demonstrate DermiSphere’s ability to support rapid dermal regeneration in a pilot in vivo swine full-thickness excisional wound model. Criteria for Success: Epidermal take ≥75% on day 21 of the study and wound contraction ≤20% and ≤30% on days 14 and 60 of the study respectively. Our Phase II study will be a full- scale, full thickness excisional swine wound model to validate DermiSphere’s efficacy over Integra. Data from this study will also be used to improve formulation for both scale manufacturing and for pre-clinical safety and efficacy testing requirements. Demonstrating DermiSphere’s superior efficacy over Integra in a full-scale wound model is currently our first major strategic milestone. Achieving this milestone will sufficiently increase the equity value of FesariusTherapeutics Inc. to attract the capital needed to scale operations for increased manufacturing, FDA submission and commercialization.