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的创新Mergo（r）制剂的开发和制造过程，以将siRNA治疗剂输送到患病细胞。ENHANCE结合了多学科合作伙伴，具有高度互补的专业知识和成功的项目交付经验，具有快速的科学和商业进展。与小分子和抗体相比，siRNA具有作用于几乎不受限制的选择的能力，否则'不可用药'的治疗靶点，具有高效力和特异性\[1\]。siRNA具有治疗一系列疾病适应症的潜力。2018-2019年Alnylam的siRNA治疗肝病的开创性监管批准\[2\]验证了此类疗法的临床和商业机会。尽管如此，目前的交付方法仍不理想由于围绕细胞特异性靶向、货物装载能力、高毒性和复杂/昂贵的制造的限制，Mergo（r）制剂（例如GalNAc-缀合物、脂质纳米颗粒、病毒载体）越来越多地用于治疗疾病，这突出了对新制剂的需求，以增加可寻址的疾病适应症[3]。Mergo（r）制剂通过其模块化设计解决了这些挑战，包括中心RNA纳米支架，其可以用治疗剂和靶向分子功能化，仅识别感兴趣的特定患病细胞上的生物标志物，进而显著降低其他细胞/组织中的毒副作用。在Mergo（r）配方证明了有希望的体外/体内结果、有竞争力的安全性和有利的成本概况之后，该技术已经达到足够的成熟度，可以开始建立配方能力的过程。反过来，这将支持和加速Mergo（r）配方的开发途径，以确保后期开发的可扩展性。ENHANCE通过基于实验的高通量策略设计来识别和解决制造瓶颈，增强制造工艺的稳健性，以提高资源效率和产量。CPI在推动制造业创新以促进技术转让方面的跨职能和量身定制的专业知识将有助于降低风险并加快上市速度，使Mergo（r）配方能够在其开发阶段安全过渡到规模扩大。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行业带来多样化的利益。[1] Lam J.K.W等人Mol\_Ther\_Nucleic\_Acids_\_2015\_4（9）：e252\. [2]Debacker A.J等人摩尔\_治疗_ 2020\_28（8）：1759-1771\. \[3\]Payne\_D\__Nature_\_574\_S1\_2019\.