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，致力于发现和开发新型肽疗法。肽代表了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，分子平衡介于小分子和蛋白质之间，但在生化和治疗上与两者不同。肽疗法通常将大生物分子的特异性和功效与小分子疗法的更小剂量、更简单的递送途径和更低的制造成本结合起来。药物发现中越来越多的人认识到需要在尽可能接近其自然环境的情况下筛选靶标（包括一系列可能包括蛋白质、基因和RNA的生物实体）。开发新型药物疗法的生物制药公司有一个**目前尚未满足但至关重要的需求**来识别既能**与靶点结合**又能**诱导功能性反应**的药物。此前，临床试验失败的主要原因一直是并且仍然是无法证明疗效；主要是由于目标的筛选脱离了其天然的生理背景。传统的筛选方法通常利用在溶液中分离的重组形式的蛋白质靶标。 Orbit 建议直接筛选细胞上的靶标，以识别不仅能结合而且能引发功能反应的肽。 Orbit 此前已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**解决其目标客户（开发肽疗法的生物/制药公司）的重大需求**，从而为新型功能性肽的发现速度提供根本性的改变。在该项目中，Orbit 将开发实施基于液滴的微流体进行细胞功能筛选的平台的关键部分。这种改变游戏规则的基于液滴的屏幕将能够对基于细胞的药物靶标进行高通量筛选，以发现**功能性**候选肽药物。这将显着减少筛选成本、劳动力和时间。该项目将解决在生物学相关背景下难以获得的药物靶点；将对药物发现和开发市场以及肽治疗市场造成干扰，使 Orbit 成为全球领先的肽药物发现公司。

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.