INDUCE: Development of siRNA-Mergo® therapeutics for lung indications.

INDUCE：开发针对肺部适应症的 siRNA-Mergo® 疗法。

• 批准号: 10072572
• 金额: $ 44.58万
• 依托单位: SIXFOLD BIOSCIENCE LTD.
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10072572
• 关键词: INDUCE; Development; siRNA; Mergo; therapeutics

INDUCE aims to develop and validate Sixfold's RNA therapeutics delivery system, Mergo?, for delivery of (simultaneously developed) short-interfering RNA (siRNA) gene silencing cargo to a specific tissue type (undisclosed). INDUCE brings together multidisciplinary, high-expertise partners with a track record of successful project completion, allowing for both fast scientific progress and commercial advancement.In comparison to small molecules and antibodies, siRNAs can act on a virtually unrestricted choice of otherwise 'undruggable' therapeutic targets, with high potency and specificity, with the potential to treat a range of disease indications \[1\]. Pioneering regulatory approvals of Alnylam's siRNA therapeutics for liver disorders in 2018-2019 \[2\] substantiated clinical and commercial opportunities for such therapies. However, current delivery approaches remain suboptimal (e.g. GalNAc-conjugates, lipid nanoparticles, viral vectors) due to limitations surrounding cell-specific targeting, cargo-loading capacity, high toxicity and complex/expensive manufacturing, highlighting the need for novel formulations to increase addressable disease indications \[3\].Mergo(r), Sixfold's proprietary delivery system, addresses these challenges through its modular design based around a central RNA nanoscaffold, which can be functionalized with therapeutics/targeting molecules to recognise biomarkers on specific cells of interest, significantly reducing toxic side-effects from the therapeutic in other cells and tissues. Following demonstration of promising technological maturity through _in vitro/in vivo_ results, additional validation of mechanism-of-action for specific tissue types is needed.INDUCE will develop an in-house therapeutic targeted towards a specific extrahepatic tissue, and exploit the versatility of Mergo(r) to improve delivery via specific tissue-targeting. In turn, INDUCE will generate in-house asset(s) whilst speeding candidate development, and act as a preclinical demonstrator for the application of Mergo(r) to target other clinical indications. Mergo(r) holds significant value-capturing potential in the thriving siRNA therapeutics and associated delivery markets, through improved safety, efficacy, and reduced cost-of-goods (particularly compared to viral technologies).Pharmidex's unique expertise in advanced preclinical drug development will enable the generation of a preclinical data-pack for rapid commercialization and clinical advancements via generation of licensing deals. Sixfold's comprehensive IP portfolio and licensing strategy engages the broader biopharmaceutical supply chain, generating diverse benefits to the wider UK life sciences sector.\[1\]Lam\_J.K.W\_et\_al.\__Mol\_Ther\_Nucleic\_Acids_\_2015\_4(9):e252\. \[2\]Debacker\_A.J\_et\_al.\__Mol\_Ther._\_2020\_28(8):1759-1771.\[3\]Payne\_D\__Nature_\_574\_S1\_2019\.

诱导的目标是开发和验证Sixfold的RNA治疗递送系统，Mergo？，用于将（同时开发的）短干扰RNA （siRNA）基因沉默货物递送到特定组织类型（未公开）。诱导汇集了多学科，高专业知识的合作伙伴，并有成功完成项目的记录，允许快速的科学进步和商业进步。与小分子和抗体相比，sirna可以作用于几乎不受限制的“不可药物”治疗靶点，具有高效力和特异性，具有治疗一系列疾病适应症的潜力\[1\]。2018-2019年Alnylam siRNA治疗肝脏疾病的开创性监管批准\[2\]证实了此类治疗的临床和商业机会。然而，由于细胞特异性靶向、载货能力、高毒性和复杂/昂贵的制造等方面的限制，目前的给药方法（例如galnac偶联物、脂质纳米颗粒、病毒载体）仍然不是最佳的，这突出了需要新的配方来增加可寻址的疾病适应症\[3\]。Sixfold的专有给药系统Mergo(r)通过其基于中心RNA纳米支架的模块化设计解决了这些挑战，该系统可以与治疗药物/靶向分子一起功能化，以识别特定细胞上的生物标志物，从而显著减少治疗药物对其他细胞和组织的毒副作用。在通过体外/体内结果证明有希望的技术成熟之后，需要对特定组织类型的作用机制进行进一步的验证。诱导将开发一种针对特定肝外组织的内部治疗方法，并利用Mergo(r)的多功能性来改善通过特定组织靶向的递送。反过来，诱导将在加速候选药物开发的同时产生内部资产，并作为Mergo(r)应用于其他临床适应症的临床前示范。Mergo(r)通过提高安全性、有效性和降低商品成本（特别是与病毒技术相比），在蓬勃发展的siRNA疗法和相关递送市场中具有巨大的价值捕获潜力。Pharmidex在先进的临床前药物开发方面的独特专业知识，将通过授权交易的产生，为快速商业化和临床进展提供临床前数据包。Sixfold全面的知识产权组合和许可战略涉及更广泛的生物制药供应链，为更广泛的英国生命科学领域带来多样化的利益。\[1\] Lam＿J.K.W＿et＿al.＿＿Mol＿Ther＿Nucleic＿Acids＿＿2015＿4(9):e252\。\[2\] Debacker＿A.J＿et＿al.＿＿Mol＿Ther.＿＿2020＿28(8):1759-1771。\[3\] Payne＿D＿＿Nature＿＿574＿S1＿2019\。