First in class to first in human: Harnessing physiological regulation mechanisms to enhance safety and efficacy of next generation bispecific antibodies

治疗性抗体是一种生物疗法，它彻底改变了我们治疗癌症和炎症性疾病的方式。Novalgen是一家新兴的免疫治疗公司，它已经开发出一种新型的智能抗体，一旦它们完成了它们的活性，就会停止发挥其治疗活性。通过这样做，NovalGen技术提供了新一代抗体疗法，具有最大的安全性和最大的有效性。我们的第一个智能抗体疗法将治疗血友病A(HA)，这是一种遗传性疾病，血液不能正常凝结，因为它缺乏足够的凝血蛋白(凝血因子)。因此，血友病患者在受伤后经历自发性出血或出血的时间比正常情况下更长。我们的新抗体药物将取代HA患者缺失的凝血因子(FVIII)，但其特殊性是，一旦帮助形成血栓，它将被灭活，以避免与不受控制的血栓相关的潜在威胁生命的副作用。在我们在人体上测试这种新药之前，我们需要在实验室进行测试，以确定其安全性和有效性。这需要一个全面的数据包来证明将这种候选药物推向临床是值得的。生物医学催化剂拨款将使NovalGen能够开发非常详细的数据包并准备临床试验申请，该申请将在项目结束时提交给英国监管机构(药品和医疗保健产品监管机构[MHRA])，以获得对血友病患者使用这种新药的许可，这是将新药推向市场的第一步。如果血友病产品清除了第一阶段临床研究的第一个障碍，那么它们在获得批准方面有非常好的记录，因此，UKRI支持这一计划的资金可能会使英国在未来的HA治疗方面走在前列。这种药物的成功将鼓励NovalGen和其他公司制造其他“智能药物”，这代表着我们治疗疾病的方式发生了一步变化。

Therapeutic antibodies are biological therapies that have revolutionised the way we treat cancer and inflammatory diseases. Novalgen, an emerging immunotherapy company, has developed a novel and smart type of antibody that stops exerting its therapeutic activity once they have completed their activity. In so doing, the NovalGen technology offers a new generation of antibody therapies with potential for maximal safety alongside maximal efficacy.Our first smart antibody therapy will treat Haemophilia A (HA), an inherited condition in which blood doesn't clot normally because it lacks sufficient blood-clotting proteins (clotting factors). Consequently, patients with haemophilia, experience spontaneous bleeds or bleed for a longer time after an injury than normal. Our new antibody drug will replace the missing clotting factor (FVIII) in patients with HA, but with the peculiarity that it will get inactivated once it has helped the formation of a blood clot, to avoid potentially life-threatening side effects associated with uncontrolled clotting.Before we test this new drug in people, we need to test it in the laboratory to establish that its safety and efficacy. This requires a comprehensive data package demonstrating that it is worth progressing this candidate drug to the clinic.The Biomedical Catalyst grant will enable NovalGen to develop very detailed data packages and prepare a clinical trial application which will be submitted to the UK regulatory agency (the Medicines and Healthcare Products Regulatory Agency \[MHRA\]) at the end of the project, to gain permission to administer this new drug to haemophilia patients, the first step in bringing a new drug to the market.Haemophilia products have a very good track record of obtaining approval if they clear the first hurdle of a Phase I clinical study, so funding from UKRI in support of this program could result in the UK being at the forefront of HA treatment in the future. Success with this drug will encourage NovalGen and other companies to make other "smart drugs" representing a step change in the way we treat diseases.