ProteinQure and Orbit Discovery are developing a new peptide discovery platform that can be commercialized as well as specific therapeutic molecules addressing key unmet needs. In particular we aim to develop novel peptide ligands using ProteinQure's Artificial Intelligence (AI) Platform to design custom libraries which will be subsequently utilised in functional screens using the Orbit Discovery screening platform. The combination of both AI and functional screening on a "library scale" is unprecedented in the current market. This project will work on two Orphan GPCRs, with disease related biology. The resulting peptides will have significant commercial value, but of even higher commercial potential is the demonstration of the combination of a proprietary screening platform and AI tools to enable therapeutics discovery for even the hardest sets of targets. These platforms offer opportunities in both a collaborative research setting or service setting with third parties.

Orbit Discovery is a UK-based SME pioneering the discovery and development of novel peptide therapeutics. Peptides represent a unique class of pharmaceutical compound, having incredibly high chemical diversity, molecularly poised between small molecules and proteins, yet biochemically and therapeutically distinct from both. Peptide therapeutics typically combine the specificity and efficacy of large biological molecules with the smaller dose-size, simpler delivery routes and lower manufacturing costs of small molecule therapeutics. The growing realisation in drug discovery is the need to screen targets (including a range of biological entities which may include proteins, genes and RNA) in as close to their natural contexts as possible. Biopharmaceutical companies developing novel drug therapies have a **currently unmet yet critical need** to identify drugs that both **bind to the target** and **induce a functional response**. Previously, the primary source of clinical trial failure has been, and remains, an inability to demonstrate efficacy; mostly due to screening of targets out of their native physiological context. Traditional screening methodologies typically make use of recombinant forms of protein targets isolated in solution. Orbit proposes to screen targets directly on cells to identify peptides that not only bind but also elicit a functional response. Orbit has previously demonstrated a proof-of-concept for its cell-based peptide library screening method which has the potential to **address a significant need** for its target customers (bio/pharmaceutical firms developing peptide therapeutics), providing a radical step-change in the speed of discovery of novel functional peptides. In this project, Orbit will develop a crucial part of the platform implementing droplet-based microfluidics for cell-functional screening. This game-changing droplet-based screen will enable high-throughput screening against cell-based drug targets for the discovery of **functional** peptide drug candidates. This will significantly reduce screening cost, labour, and time. The project will address difficult to access drug targets in biologically relevant contexts; will cause disruption to the drug discovery and development markets as well as the peptide therapeutics market, positioning Orbit as the leading peptide drug discovery company globally.