High throughput cell-based functional screening platform for peptide drug discovery

Orbit Discovery是一家总部位于英国的中小企业，率先发现和开发新型多肽疗法。多肽是一类独特的药物化合物，具有令人难以置信的高度化学多样性，分子上位于小分子和蛋白质之间，但在生化和治疗方面与两者截然不同。多肽疗法通常将大生物分子的特异性和有效性与小分子疗法的更小剂量、更简单的给药路线和更低的制造成本结合在一起。药物发现中越来越多的人意识到，需要在尽可能接近其自然环境的情况下筛选靶标(包括一系列生物实体，可能包括蛋白质、基因和RNA)。开发新药物疗法的生物制药公司有一个**目前尚未得到满足的关键需求**，即**与靶标结合**和**诱导功能性反应**的药物。以前，临床试验失败的主要原因一直是，现在仍然是，无法证明疗效；主要是因为筛选出了不同于其天然生理背景的靶点。传统的筛选方法通常利用分离于溶液中的重组形式的蛋白质靶标。Orbit建议直接在细胞上筛选靶标，以识别不仅结合而且能引起功能性反应的多肽。Orbit之前已经展示了其基于细胞的肽库筛选方法的概念验证，该方法有可能**满足其目标客户(开发肽疗法的生物/制药公司)的重大需求，使发现新功能肽的速度发生根本变化。在这个项目中，Orbit将开发平台的关键部分，实现基于液滴的微流控技术，用于细胞功能筛选。这种改变游戏规则的基于液滴的筛选将能够针对基于细胞的药物目标进行高通量筛选，以发现**功能性**多肽药物候选药物。这将大大减少筛选成本、人力和时间。该项目将解决在生物相关背景下难以获得药物靶标的问题；将对药物发现和开发市场以及多肽治疗市场造成干扰，使轨道公司成为全球领先的多肽药物发现公司。

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.