Development of a breakthrough anti-fibrotic gene therapy to improve surgical outcomes and reduce re-admission rates for patients with severe glaucoma.

开发突破性抗纤维化基因疗法，以改善严重青光眼患者的手术结果并降低再入院率。

• 批准号: 33541
• 金额: $ 44.12万
• 依托单位: NANOGENICS LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=33541
• 关键词: Development; breakthrough; anti; fibrotic; gene

Lifetime risk of permanent sight loss or blindness was estimated to be 1/5 of people globally (DeloitteAccessEconomics-2017). \>2M people(UK) live with sight loss significant enough to have a drastic impact upon their daily lives, with the cost estimated at £28.1Bn (RNIB-2017). Glaucoma is the second leading cause of blindness, with 500,000 UK residents affected by open-angle Glaucoma.Current treatments for Ocular Fibrosis prevention are Mitomycin-C and 5- Fluorouracil, both of which were originally intended for use in chemotherapy and are used off-label (not intended use-case). Such treatments have limitations including poor targeting, increased off-target cytotoxicity leading to drastic side effects (blindness, tissue-damage, infection). The development of a targeted ocular fibrosis prevention treatment is considered one the greatest unmet needs in clinical ophthalmology (Expert.Rev.Opthamol.10:65-76).NanoGenics are a SME specialising in the development of drug delivery technologies and have used over 90 years of combined experience to address key barriers effecting their wide-scale adoption. NanoGenics have developed LipTide-ECP105, an innovative Ocular Fibrosis prevention treatment at a competitive price which is suitable for global market implementation that uniquely offers:\*Payload protection within peptide nanoparticle surround by a lipid layer to facilitate endosomal release.\*Targeted delivery using specific peptide sequences displayed on the surface.\*Completely novel siRNA sequence targeted at reduce fibrosis and scarring in post-glaucoma surgery.LipTide-ECP105 will revolutionise post-surgical Glaucoma treatment using targeted therapeutics that reduce toxic side-effects and cost associated with topical treatments, with broad drug delivery potential. Glaucoma therapeutics market is estimated to be worth \>$7.6Bn by 2026(CAGR:2.9%)(TransparencyMarketResearch-2018), with ophthalmology being a clear initial route to market for gene therapy technologies (Spark-Therapeutics&Nightstar-Therapuetics).NanoGenics aim to address this unmet need through the development of LipTide-ECP105, an innovative drug delivery method at a competitive price, suitable for global market implementation that uniquely offers:\*Payload protection within peptide nanoparticle surround by a lipid layer to facilitate endosomal release.\*Targeted delivery using specific peptide sequences displayed on the surface displayed in the cysteine loop.\*Completely novel siRNA sequence targeted at reduce fibrosis and scarring in post-glaucoma surgery.Building on successful _in vitro_ and _in vivo_ studies with initial toxicology/efficacy results proven, a 15-month programme of research is required to prepare LipTide-ECP105 for human clinical trials. LipTide platform also offers vast potential as a breakthrough gene therapy delivery route within the drug delivery market, offering many advantages to treat a broad range of indications (e.g.neuroblastoma/cystic fibrosis/cancer-to be explored) over traditional Adeno-Associated Virus (AAV)/lentivirus payload delivery.

据估计，全球有 1/5 的人终生面临永久性视力丧失或失明的风险（DeloitteAccessEconomics-2017）。 \>200 万人（英国）的视力丧失严重到足以对他们的日常生活产生巨大影响，损失估计为 281 亿英镑 (RNIB-2017)。青光眼是导致失明的第二大原因，有 500,000 名英国居民受到开角型青光眼的影响。目前预防眼纤维化的治疗方法是丝裂霉素-C 和 5-氟尿嘧啶，这两种药物最初旨在用于化疗，但在标签外使用（非预期用例）。此类治疗具有局限性，包括靶向性差、脱靶细胞毒性增加，导致严重的副作用（失明、组织损伤、感染）。开发有针对性的眼部纤维化预防治疗被认为是临床眼科中最大的未满足需求之一 (Expert.Rev.Opthamol.10:65-76)。NanoGenics 是一家专门从事药物输送技术开发的中小企业，并利用 90 多年的综合经验来解决影响其广泛采用的关键障碍。 NanoGenics 开发了 LipTide-ECP105，这是一种价格具有竞争力的创新性眼部纤维化预防治疗药物，适合全球市场实施，其独特之处在于：\*肽纳米颗粒内的有效负载保护，周围有脂质层，以促进内体释放。\*使用表面显示的特定肽序列进行靶向递送。\*针对减少眼部纤维化和疤痕形成的全新 siRNA 序列 LipTide-ECP105 将使用靶向疗法彻底改变术后青光眼治疗，减少与局部治疗相关的毒副作用和成本，并具有广泛的药物输送潜力。预计到 2026 年，青光眼治疗市场价值将超过 76 亿美元（复合年增长率：2.9%）（TransparencyMarketResearch-2018），其中眼科是基因治疗技术进入市场的明确初始途径（Spark-Therapeutics 和 Nightstar-Therapuetics）。NanoGenics 旨在通过开发 LipTide-ECP105（一种创新药物）来解决这一未满足的需求。 药物输送方法价格有竞争力，适合全球市场实施，独特地提供：\*肽纳米粒子内的有效负载保护，周围有脂质层，以促进内体释放。\*使用半胱氨酸环中显示的表面上显示的特定肽序列进行靶向输送。\*全新的 siRNA 序列，旨在减少青光眼手术后的纤维化和疤痕形成。建立在成功的基础上 经过_体外_和_体内_研究并得到初步毒理学/功效结果证明，需要一个为期15个月的研究计划来准备用于人体临床试验的LipTide-ECP105。 LipTide 平台还作为药物输送市场中突破性的基因治疗输送途径提供了巨大的潜力，与传统的腺相关病毒 (AAV)/慢病毒有效负载输送相比，它具有许多优势，可以治疗广泛的适应症（例如神经母细胞瘤/囊性纤维化/有待探索的癌症）。