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。新兴的免疫治疗公司Novalgen开发了一种新型智能抗体，一旦完成其治疗活性，就会停止发挥其治疗活性。因此，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疗效。我们的首个智能抗体疗法将用于治疗A型血友病（HA），这是一种遗传性疾病，患者的血液由于缺乏足够的凝血蛋白（凝血因子）而无法正常凝血。因此，血友病患者在受伤后会自发性出血或出血时间比正常人长。我们的新抗体药物将取代HA患者体内缺失的凝血因子（FVIII），但它的特点是，一旦它帮助形成血凝块，它将被灭活，以避免与不受控制的凝血相关的潜在危及生命的副作用。在我们对这种新药进行人体试验之前，我们需要在实验室进行试验，以确定其安全性和有效性。这需要一个全面的数据包，证明值得将这种候选药物推向临床。生物医学催化剂的资助将使NovalGen能够开发非常详细的数据包，并准备一份临床试验申请，该申请将在项目结束时提交给英国监管机构（药品和保健产品监管机构\[MHRA\]），以获得对血液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。血友病产品有一个非常好的记录，如果它们清除了I期临床研究的第一个障碍，就会获得批准，因此UKRI的资金支持该计划可能会使英国在未来处于HA治疗的前沿。这种药物的成功将鼓励诺valgen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重大变化。

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.