ENHANCE: Scaling up development of novel Mergo® formulations via optimised synthesis and high-throughput strategies

增强：通过优化合成和高通量策略扩大新型 Mergo® 配方的开发

• 批准号: 10070133
• 金额: $ 49.12万
• 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=10070133
• 关键词: ENHANCE; Scaling; up; development; novel

ENHANCE aims to improve the development and manufacturing process of Sixfold's innovative Mergo(r) formulations for the delivery of siRNA therapeutics to diseased cells. ENHANCE combines multidisciplinary partners with highly complementary expertise and successful project delivery experience, with rapid scientific and commercial progress.Compared to small-molecules and antibodies, siRNAs hold the ability to act on a virtually unrestricted choice of otherwise 'undruggable' therapeutic targets, with high potency and specificity \[1\]. siRNAs have the potential to treat a range of disease indications. Pioneering regulatory approvals of Alnylam's siRNA therapeutics for liver disorders in 2018-2019 \[2\] validated clinical and commercial opportunities for such therapies. Nevertheless, 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) formulations address these challenges through their modular design, comprising a central RNA-nanoscaffold that can be functionalized with therapeutics and targeting molecules, recognizing biomarkers on specific diseased cells of interest only, in turn significantly reducing toxic side-effects in other cells/tissues. Following promising _in vitro/in vivo_ results, competitive safety and favourable cost-profiles demonstrated by Mergo(r) formulations, the technology has reached sufficient maturity to initiate the process of building upon formulation capabilities. In turn, this will support and accelerate the development pathways for Mergo(r) formulations to ensure scalability in later-stage development.ENHANCE identifies and addresses manufacturing bottlenecks via Design of Experiments-based high-throughput strategies, enhancing the robustness of manufacturing processes to improve resource efficiency and throughput. CPI's cross-functional and tailored expertise in advancing innovations in manufacturing for tech transfer will help de-risk and accelerate the route to market, enabling Mergo(r) formulations to make a secure transition in its development stages to scale up.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\.

ENHANCE 旨在改进 Sixfold 创新 Mergo(r) 配方的开发和制造流程，以向患病细胞提供 siRNA 治疗药物。 ENHANCE 将具有高度互补的专业知识和成功的项目交付经验的多学科合作伙伴结合在一起，并取得了快速的科学和商业进展。与小分子和抗体相比，siRNA 能够作用于几乎不受限制的“不可成药”治疗靶点的选择，具有很高的治疗效果。效力和特异性\[1\]。 siRNA 具有治疗一系列疾病适应症的潜力。 Alnylam 的 siRNA 肝脏疾病疗法于 2018-2019 年获得监管部门的首创性批准，[2] 验证了此类疗法的临床和商业机会。然而，由于细胞特异性靶向、货物装载能力、高毒性和复杂/昂贵的制造等方面的限制，目前的递送方法仍然不够理想（例如 GalNAc 缀合物、脂质纳米粒子、病毒载体），这凸显了对新制剂的需求，以增加可寻址能力疾病适应症\[3\]。Mergo(r) 配方通过其模块化设计解决了这些挑战，其中包括一个中央 RNA 纳米支架，可以通过治疗剂和靶向分子进行功能化，识别生物标志物仅针对感兴趣的特定患病细胞，从而显着减少其他细胞/组织的毒副作用。 Mergo(r) 配方展现出有希望的_体外/体内_结果、具有竞争力的安全性和有利的成本概况，该技术已达到足够的成熟度，可以启动建立配方能力的过程。反过来，这将支持并加速 Mergo(r) 配方的开发路径，以确保后期开发的可扩展性。ENHANCE 通过基于实验设计的高通量策略识别和解决制造瓶颈，增强制造工艺的稳健性提高资源效率和吞吐量。 CPI 在推进制造创新和技术转让方面拥有跨职能和量身定制的专业知识，这将有助于降低风险并加速进入市场的进程，使 Mergo(r) 配方能够在其开发阶段安全过渡以扩大规模。Sixfold 全面的知识产权组合许可策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种利益\[1\]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\。 \[3\]佩恩\_D\__自然_\_574\_S1\_2019\。