Intellegens: Developing a novel ML-driven tool to advance Oligonucleotide-therapeutic characterisation and manufacturing.

英特尔公司正在寻求开发一种新型的ML动力数字工具，为组织提供用于寡核苷酸表征和杂质预测的用户界面。英特尔将与过程创新中心（CPI）合作，建立一个广泛的相关结构数据库，并将定义和编码到软件中的智能查找逻辑用于创建靶分子的特定配置文件。核酸疗法（NAT）是一种主要的新兴药物，为治疗一系列常见和罕见疾病提供了巨大的潜力，通常缩短了开发时间，比其他类别的药物更快。此外，NAT提供了根据患者的基因组序列为个体患者定制治疗的机会。然而，NAT的广泛临床应用可能受到当前制造和递送方法的限制。寡核苷酸分为几类，包括反义、核酶、适体、miRNA、CPG/免疫刺激和RNAi。目前，寡核苷酸疗法针对许多治疗领域和适应症，从肿瘤（29%）、中枢神经系统（CNS）疾病（12%）和遗传性疾病（9%）到心血管、呼吸系统、眼科、胃肠道和感染性疾病。全球寡核苷酸开发管道目前有660个处于临床前阶段，70个处于1期阶段，94个处于2期阶段，19个处于3期阶段，13个处于上市阶段，其中更大比例的目标人群为50万以上的患者群体。40%的批准发生在5年内（例如Inclisiran），提供了寡核苷酸是有效治疗领域的积极信号/置信度[NICE，2021]。为小分子设计的杂质预测工具还不足以预测寡核苷酸的杂质。随着对机制的理解和筛选方法的改进，可以鉴定出具有更好安全性的更有效的寡核苷酸候选物，用于治疗越来越多的疾病和患者人群。最近批准的寡核苷酸治疗剂的激增表明了即将到来的潜力，因为寡核苷酸具有中等大小，与小分子相比，对靶标的选择性大大提高，脱靶效应更少[Thakur，2022]。Intelaps解决了对能够预测杂质并表征寡核苷酸的大型和复杂性质的数字工具的未满足的市场需求。随后，降低开发成本并促进制造规模扩大。

Intellegens Ltd is seeking to develop a novel ML-powered digital tool to provide organisations with a user interface for oligonucleotide characterisation and impurity prediction. Intellegens will collaborate with the Centre for Process Innovation (CPI) to build an extensive database of associated structures and intelligent look-up logic defined and coded into the software to create specific profiles for target molecules.Nucleic Acid Therapies (NATs) is a major emerging new class of medicines, offering enormous potential to treat a range of common and rare diseases with typically reduced timescales for development that can be quicker than other classes of drugs. In addition, NATs provide opportunities to tailor treatments to individual patients based on their genome sequence. However, the broader clinical application of NATs can be limited by current methods of manufacture and delivery.Oligonucleotides are segmented into several classes, including antisense, ribozymes, aptamers, miRNA, CPG/Immunostimulatory and RNAi. Many therapeutic areas and indications are currently targeted by oligo therapies from oncology (29%), Central Nervous System (CNS) disorders (12%) and genetic disorders (9%) to cardiovascular, respiratory, ophthalmology, gastrointestinal and infectious diseases. The global oligonucleotide development pipeline currently has 660 in preclinical, 70 phase-1, 94 phase-2, 19 phase-3 and 13 marketed, with a larger proportion targeting patient populations \>500k. 40% of approvals have occurred within 5-years (e.g. Inclisiran), providing a positive signal/confidence that oligonucleotides are a valid therapeutic area \[NICE,2021\]. This is encouraging more investment at the discovery end.Impurity prediction tools designed for small molecules are not sophisticated enough to predict impurities for oligonucleotides. With improved mechanistic understanding and screening approaches, more potent oligo candidates with better safety profiles can be identified for treatment of an increasing range of diseases and patient populations. The recent surge in approved oligonucleotide therapeutics indicates imminent potential as oligos are of intermediate size with much-improved selectivity towards the target and fewer off-target effects than small molecules \[Thakur,2022\].Intellegens addresses the unmet market need for a digital tool capable of impurity prediction and characterisation of the large and complex nature of oligonucleotides. Subsequently, reducing development costs and facilitating manufacturing scale-up.