A multivalent, easy-to-use product to mitigate and treat radiation exposure

摘要 辐射和核事故或攻击的威胁需要有效的辐射医学对策。 (MCM)能够减轻和治疗暴露于电离辐射的影响。造血型急性放射 综合征(HRAS)和皮肤辐射综合征(CRS)对接触者构成严重的生命威胁 个人。目前没有有效的放射缓释剂(在辐射暴露后但在组织之前使用 毒性表现)或放射治疗(在组织毒性表现后给予)尚未 获得了FDA的批准。纤维板公司开发的纤维板-S(FPS)，一种静脉注射解决方案 纤维蛋白原包被的白蛋白纳米球最初是为了增强 临床环境。对受辐射的啮齿动物进行的初步研究表明，在辐射后给予Fas 电离辐射暴露作为一种抗辐射的多价MCM具有独特的潜力。尤其是，它是 证明FPS对放射性皮肤损伤(RSI)具有预防作用。在.期间 在SBIR第一阶段项目中，进行了一项大鼠临床前可行性研究，以证明FPS作为一种 RSI的治疗。实现了几个目标：1)FPS作为预防措施的有效性 并展示了对RSI的治疗方法。2)FPS诱导的干细胞向 观察损伤情况。3)FPS对中性粒细胞减少症和血小板减少症有一定的缓解作用。 4)发现FPS对细胞因子的调节作用。第一阶段取得的成果代表了 这是SBIR第二阶段项目的完美起点，将进行更多的临床前研究和 根据The Animal的说法，用于完成IND提交给FDA的包，以寻求FDA的批准 功效法则。在SBIR第二阶段项目中，Fibroboard的目标是：i)展示FPS作为一种治疗药物的疗效 小型猪RSI的治疗，作为第二个动物模型。Ii)评估FPS在大鼠中的毒理学特征，III)评估FPS 稳定性和保质期，iv)扩大当前的制造工艺，以达到足以 持续临床发展。获得FDA对FPS的批准将为将其纳入 国家战略储备，作为放射性/核紧急情况下的MCM。 1

ABSTRACT The threat of radiological and nuclear accidents or attacks demands effective radiation medical countermeasures (MCM) able to mitigate and treat the effects of exposure to ionizing radiations. Hematopoietic acute radiation syndrome (HRAS) and cutaneous radiation syndrome (CRS) pose severe, life-threatening risks to exposed individuals. Currently no effective radio-mitigator (to be administered after radiation exposure but prior to tissue toxicity manifestation) or radio-therapeutic (to be administered after tissue toxicity manifestation) has yet received FDA approval. Fibroplate, Inc. developed Fibrinoplate-S (FPS), an intravenous injectable solution of Fibrinogen-coated Albumin nano-Spheres originally developed to augment hemostatic functions in multiple clinical settings. Preliminary studies conducted on irradiated rodents suggested that FAS administered after ionizing radiation exposure has a unique potential as a multi-valent MCM against radiations. In particular, it was demonstrated that FPS has prophylactic properties against Radiation-induced Skin Injuries (RSI). During the SBIR Phase I project, a preclinical feasibility study in rats was performed to demonstrate FPS’ efficacy as a therapeutic treatment for RSI. Several objectives were accomplished: 1) The efficacy of FPS as both prophylactic and therapeutic treatment for RSI was demonstrated. 2) An FPS-induced stem cells mobilization towards the lesion was observed. 3) The efficacy of FPS as a mitigator for neutropenia and thrombocytopenia was confirmed. 4) A regulatory effect of FPS on the cytokine profile was discovered. Results obtained in Phase I represent the perfect starting point for this SBIR Phase II project, where additional preclinical studies will be performed and used to complete an IND submission package to the FDA, to pursue FDA approval according to the Animal Efficacy Rule. In this SBIR Phase II project, Fibroplate aims at: i) Demonstrate FPS efficacy as a therapeutic treatment for RSI in minipigs, as a second animal model. ii) Assess FPS toxicology profile in rats, iii) Assess FPS stability and shelf-life, iv) Scale-up current manufacturing process to reach production volumes sufficient to sustain the clinical development. Obtaining FDA approval for FPS will pave the way for its inclusion in the Strategic National Stockpile as MCM for radiological/nuclear emergencies. 1