Public Funding for Pepgen Limited

Nucleic acid drugs are genomic medicines with the potential to transform human healthcare. Research has indicated that such therapeutics could have applications across a broad range of disease areas, including degenerative disorders, rare disorders and cancer. The use of this technology is highly promising, yet **the main challenge impeding the clinical translation of nucleic-acid based drugs is drug delivery itself**. The aim of PepGen is to meet this delivery challenge. The technology underpinning PepGen's approach is to **harness the drug delivery properties of small protein fragments known as cell-penetrating peptides (CPPs)**. These peptides can be attached to nucleic-acid based drugs in order to improve the delivery of these cargo molecules to their site of action. Antisense oligonucleotides (ASOs) are a subtype of nucleic acid drugs that modulate how the information within a gene is processed in the cell. ASOs bind to specific sites in the genome and allow genetic information to be 'skipped' over in order to mask underlying mutations. This project supports the development of a CPP-ASO conjugate drug. The advantage of PepGen's novel CPPs is that **efficacy and toxicology are decoupled in these peptides**. As such, our CPPs are known to elicit highly effective delivery with dramatic reductions in the associated side effects often seen with other molecules in this class. It should be emphasised that this is a **truly innovative step-change**, and puts PepGen at the forefront of both drug delivery technology and nucleic acid therapeutics. This 20-month project funds the work needed for PepGen to advance a lead candidate towards the clinic, with the support of Innovate UK having a considerable impact on the development timelines of this project. To conclude, the major barrier to realising the full potential of nucleic acid drugs across a broad range of therapeutic areas is drug delivery. This project will develop a disruptive technology that delivers nucleic acid drugs to their site of therapeutic action, and we expect this work to have a transformative impact on human healthcare.