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\.

诱使旨在开发和验证六倍的RNA疗法传递系统Mergo？，用于递送（同时开发的）短路RNA（siRNA）基因沉默的货物（未公开）。诱导将成功的项目完成的往绩汇集在一起​​，允许快速的科学进步和商业进步。与小分子和抗体相比，SirNA可以采取实际上无限制地选择“不可用的”治疗方法。具有高效力和特异性的目标，有可能治疗一系列疾病适应症\ [1 \]。 2018 - 2019年对Alnylam siRNA治疗肝脏疾病的开创性监管批准[2 \]证实了此类疗法的临床和商业机会。然而，由于围绕细胞特异性靶向的限制，货物载荷能力，高毒性和复杂/昂贵的制造，目前的交付方法仍然是次优的（例如Galnac-Conjugates，lipid纳米颗粒，病毒向量）疾病的适应症\ [3 \]。六倍的专有输送系统Mergo（R）通过基于中央RNA纳米命中率的模块化设计解决了这些挑战，可以通过治疗剂/靶向分子功能化，以识别有关感兴趣的特定细胞的生物标志物，显着降低了其他细胞和组织中治疗性的有毒副作用。在证明了通过_通过_in _in/in Vivo_结果表明有希望的技术成熟度后，需要对特定组织类型的行动机理进行其他验证。诱导将开发针对特定肝外组织的内部治疗性，并利用Merogo的多功能性（R）通过特定的组织靶向改善分娩。反过来，诱导会在加快候选人发展的同时产生内部资产，并充当临床前示威者，用于应用Migo（R）以针对其他临床指示。 Mergo（R）通过提高的安全性，功效和货物成本降低（尤其是与病毒技术相比），在蓬勃发展的siRNA治疗和相关的交付市场中拥有巨大的价值潜力。Pharmidex在先进的临床前药物开发方面的独特专业知识将会通过生成许可交易，可以生成一个快速商业化和临床进步的临床前数据包。 SixFold的全面IP投资组合和许可策略与更广泛的生物制药供应链相关，从而为更广泛的英国生活科学领域带来了多样的好处。 \ _4（9）：E252 \。 \ [2 \] debacker \ _a.j \ _et \ _Al。 。