Unlocking discovery of next-generation multispecific biologics for targeted cancer therapies

单克隆抗体已成为治疗晚期癌症的标准药物；然而，耐药性（无论是原发性的还是后天的）是一个主要问题。单特异性抗体的临床疗效仍然有限，特别是在晚期实体瘤的情况下。多特异性生物制剂在克服单特异性抗体的治疗缺陷方面显示出巨大的希望。通过结合位点靶向多种信号通路，多特异性抗体降低了原发性或获得性耐药的可能性，提高了临床疗效，预防和/或延缓了发病机制。最重要的是，多特异性生物制剂使新的作用机制能够根除癌细胞，否则传统抗体是不可能的。迄今为止，已有7种双特异性抗体获得市场批准，50多种抗体正在临床试验中。然而，由于缺乏高通量的多特异性组装和筛选技术，多特异性生物制剂的发现仍然受到严重限制。由于潜在靶标的数量、组合粘合剂/格式空间和复杂（通常未知的）作用机制，多特异性的发现变得更加复杂。LiliumX是一家总部位于英国的初创企业（SME），于2021年从牛津大学剥离出来，由Arne Scheu博士和Irsyad Khairil共同创立。我们已经开发了一种革命性的专有平台技术，用于高通量组装和多特异性生物制剂的筛选。我们已经从Y Combinator和Creative Destruction Lab毕业，提交了专利申请来保护我们的通用组装平台，并从领先的风险投资家那里筹集了投资。有了Smart基金，我们将进一步开发和验证我们的多特异性生物制剂发现通用装配平台的性能，证明我们可以通过从发现到体内研究的管道创造可行的资产。50年来，英国在单克隆抗体药物研发方面一直处于世界领先地位。创新英国智能资金用于开发和验证LiliumX的通用装配平台，将使英国在未来50年引领下一代多特异性生物制剂的开发和商业化。

Monoclonal antibodies have emerged as the Standard of Care for late-stage cancers; however, resistance (whether primary or acquired) is a major issue. Clinical efficacy of monospecific antibodies remains limited, particularly in the case of advanced solid tumours.Multispecific biologics show great promise in overcoming the treatment shortcomings of monospecific antibodies. With binding sites targeting multiple signalling pathways, multispecific antibodies decrease the likelihood of primary or acquired resistance and increase clinical efficacy, preventing and/or delaying pathogenesis. Most importantly, multispecific biologics enable new mechanisms of action to eradicate cancer cells, not otherwise possible with traditional antibodies. To date, seven bispecific antibodies have received market approval and over 50 are in clinical trials.However, the discovery of multispecific biologics remains severely restricted by the lack of high-throughput assembly and screening technologies for multispecifics. Discovery of multispecifics is further complicated by the number of potential targets, combinatorial binder/format spaces, and complex (often unknown) mechanisms of action.LiliumX is a UK-based start-up (SME), spun out from the University of Oxford in 2021, co-founded by Drs Arne Scheu and Irsyad Khairil. We have developed a transformative and proprietary platform technology for high-throughput assembly and screening of multispecific biologics. We have graduated from Y Combinator and Creative Destruction Lab, filed a patent application to protect our Universal Assembly Platform, and raised investment from leading venture capitalists.With Smart funding, we will further develop and validate the performance of our Universal Assembly Platform for multispecific biologics discovery, demonstrating that we can create viable assets, through the pipeline from discovery to _in vivo_ studies.For 50 years, the UK has led the world in developing monoclonal antibody drugs. Innovate UK Smart funding to develop and validate LiliumX's Universal Assembly Platform will position the UK to lead the way for the next 50 years, developing and commercialising next-generation multispecific biologics.