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

Enhance的目标是改进Six公司创新的Mergo(R)配方的开发和制造工艺，用于向患病细胞输送siRNA疗法药物。Enhance结合了具有高度互补性的专业知识和成功的项目交付经验的多学科合作伙伴，以及快速的科学和商业进展。与小分子和抗体相比，siRNAs具有几乎不受限制地选择否则无法用药的治疗靶点的能力，具有高效力和特异性。SiRNA有可能治疗一系列疾病的适应症。Alnylam的siRNA疗法在2018-2019年率先获得监管部门的批准，用于治疗肝病，[2]证实了此类疗法的临床和商业机会。然而，由于细胞特异性靶向、载货能力、高毒性和复杂/昂贵制造的限制，目前的递送方法仍然不是最优的(例如GalNAc结合物、脂质纳米粒、病毒载体)，突出了对新制剂的需求，以增加可寻址的疾病适应症。Mergo(R)制剂通过其模块化设计来解决这些挑战，包括可与治疗和靶向分子一起功能化的中心RNA纳米支架，仅识别感兴趣的特定疾病细胞上的生物标记物，从而显著减少其他细胞/组织中的毒副作用。Mergo(R)配方证明了良好的体外/体内结果、具有竞争力的安全性和有利的成本概况，这项技术已经足够成熟，可以开始建立配方能力的过程。反过来，这将支持和加快Mergo(R)配方的开发途径，以确保后期开发的可扩展性。Enhance通过设计基于实验的高通量策略来识别和解决制造瓶颈，增强制造过程的健壮性，以提高资源效率和生产能力。CPI在推进制造创新以进行技术转移方面的跨职能和量身定做的专业知识将有助于降低风险并加快进入市场的道路，使MERGO(R)配方能够在其开发阶段进行安全过渡，以扩大规模。sector.\[1\]Lam\_J.K.W\_et\_al.\__Mol\_Ther\_Nucleic\_Acids_\_2015\_4(9)：e252\.的全面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公司带来各种好处。\[2\]Debacker\_A.J\_et\_al.\__Mol\_Ther._\_2020\_28(8)：1759-1771\.[3]佩恩·D·自然·574···

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\.