ENHANCE: Scaling up development of novel Mergo® formulations via optimised synthesis and high-throughput strategies
Lead Participant:
SIXFOLD BIOSCIENCE LTD.
Abstract
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\.
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\.
Lead Participant | Project Cost | Grant Offer |
|---|---|---|
| SIXFOLD BIOSCIENCE LTD. | £418,902 | £ 293,231 |
Participant |
||
| CENTRE FOR PROCESS INNOVATION LIMITED | £92,270 | £ 92,270 |
| CPI INNOVATION SERVICES LIMITED | ||
| INNOVATE UK |
People |
ORCID iD |
| Anna Perdrix Rosell (Project Manager) |