DermiSphere: An Advanced Dermal Regeneration Scaffold for Reconstructive Surgery, PHASE II

摘要 就其本身而言，人体无法进行真皮再生。如果处理不当， 皮肤创伤（表皮和真皮的损失）通过周围皮肤的收缩和瘢痕形成而愈合， 这可能最终导致慢性创伤、永久性损伤、毁容和患者痛苦。为 多年来，金标准治疗一直是自体组织移植（患者作为自己的供体）， 但供皮区可用性不足，中厚皮片继发挛缩， 发病率使外科医生需要替代品。2000年代初，工程治疗出现， 现在的年销售额从5亿美元到10亿美元，每年增长8-12%。市场领导者Integra™ 愈合速度和程度以及挑战性治疗的有效性降低的几个缺点 伤口DermiSphere™，本申请的申报产品是一种植入式皮肤再生药物， scaffold支架that addresses解决these concern关注. DermiSphere（DS）获得专利的3D图案化微架构导向器 细胞从伤口床快速渗透到支架中，导致快速血管化和新真皮 阵我们之前的研究用DS原型治疗了临床相关的啮齿动物和猪伤口， 与Integra相比，显示出改善的性能（分别为>75%移植物摄取率与~50%）， 减少出血，增强移植物活力和真皮厚度增加40%。这些都表明 更好的临床效果。完成第二阶段的建议将导致一个冻结的DS设计， 用于FDA 510（k）批准要求的生物相容性和确认试验。此外，这个冷冻 将在临床相关猪全层伤口中确认设计相对于Integra的上级性能 模型具体而言，该研究将评估NIH iCorps计划期间确定的价值主张 与Integra相比，移植物“采集”时间/发生率和伤口挛缩改善≥20%。在第二阶段，我们将 完成两个特定目标1：优化DS的设计冻结。DS是两层：聚硅氧烷（硅酮） 层和I型胶原支架（由散装胶原和包埋的胶原微球组成）。这 aim包含四项任务来开发用于商业用途的设备的“最终”版本：（1）和（2） 使用符合cGMP的胶原蛋白来源优化微球尺寸和交联以及散装胶原蛋白， 设备;（3）优化闭合层以供临床使用;（4）制定最终灭菌参数 而不会对DS产生不利影响。将使用大鼠全厚度模型筛选所得原型的有效性。 创伤模型2：向市场领导者展示优势，并达到/超过我们的绩效价值 在猪的临床相关全层切除模型中的建议。一个优化的DS， 在全尺寸（猪）伤口模型中具有优于Integra的上级功效的设计是目前第一个主要的 战略里程碑。这将充分增加FesariusTherapeutics Inc.的股权价值。吸引 cGMP生产、FDA提交和商业化规模化运营所需的资本。

ABSTRACT On its own, the human body is incapable of dermis regeneration. If not properly treated, large full-thickness skin wounds (loss of epidermis and dermis) heal through contraction of surrounding skin and scar formation, which may ultimately lead to chronic wounds, permanent damage, disfigurement and patient suffering. For years, the gold-standard treatment has been autologous tissue transfer (a patient serving as their own donor), but insufficient donor site availability, secondary contracture of split thickness skin grafts and major donor-site morbidity leaves surgeons wanting alternatives. In the early 2000's, engineered treatments emerged, which now have annual sales from $500MM to $1BN, growing 8-12% annually. The market leader, Integra™, has several shortcomings in both the rate and degree of healing as well as decreased effectiveness in challenging wounds. DermiSphere™, the proposed product of this application is an implantable dermal regenerative scaffold that addresses these concerns. DermiSphere's (DS) patented 3D patterned microarchitecture guides rapid cell penetration from the wound bed into the scaffold, leading to swift vascularization and neo-dermis formation. Our previous studies treated clinically-relevant rodent and pig wounds with a DS prototype, and demonstrated improved performance as compared to Integra (>75% graft take vs. ~50% respectively), decreased hemorrhage, enhanced graft vitality and a 40% increase in dermal thickness. These all indicate better clinical outcomes. Completion of this Phase II proposal will result in a frozen DS design that will then be used in biocompatibility and validation testing as required for FDA 510(k) clearance. Furthermore, this frozen design will be validated for superior performance versus Integra in a clinically relevant pig full-thickness wound model. Specifically, the study will evaluate the value proposition determined during the NIH iCorps program of ≥20% improvement in graft “take” time/incidence and wound contracture vs. Integra. In Phase II, we will complete two Specific Aims 1: Design Freeze for the optimized DS. DS is two layers: a polysiloxane (silicone) layer and a type I collagen scaffold (comprised of bulk collagen and embedded collagen microspheres). This aim contains four tasks to develop the “final” version of the device meant for commercial use: (1) & (2) Optimize microsphere size and crosslinking and bulk collagen using cGMP compliant collagen sources and equipment; (3) Optimize the occlusive layer for clinical use; (4) Develop terminal sterilization parameters without adversely affecting DS. The resulting prototypes will be screened for efficacy using a rat full-thickness wound model. 2: Demonstrate superiority to the market leader and meet/exceed our performance value proposition in the clinically-relevant, full-thickness excisional model in swine. An optimized DS with a frozen design that has superior efficacy over Integra in a full-scale (porcine) wound model is currently the first major strategic milestone. This will sufficiently increase the equity value of FesariusTherapeutics Inc. to attract the capital needed to scale operations for cGMP manufacturing, FDA submission and commercialization.