Harnessing FDC technology for metastatic colorectal cancer (mCRC)

安提科生物医药公司正在开创一种名为OptiLink的创新药物输送平台，该平台是为实体肿瘤量身定做的。它的独特之处在于，它利用专门设计的小格式、肿瘤特异性抗体和适当设计的连接物，专门将强大的细胞毒有效载荷输送到肿瘤深处。与使用全尺寸抗体-药物结合物(ADC)的竞争对手不同，安提科的技术能够开发出更小的片段-药物结合物(FDC)。这些产品具有许多优势：FDC产品可能具有更高的癌症治疗指数，因为它们更有效，可以更积极地给药，因为它们更快地从正常组织中清除，快速深入到肿瘤中，从而能够更快、更有效地破坏肿瘤。通过之前的Innovate-UK支持，安提科扩展和改进了其技术，并发现了针对胃癌的强大的临床前FDC候选药物(ANT-045)，目前正在进入正式的IND使能研究，预计在18个月内提交监管文件。安提科现在正在将其流水线扩展到另一种难以治疗的实体肿瘤-结直肠癌(CRC)。虽然本质上是胃肠道，但这对胃部有非常不同的挑战。针对结直肠癌的明确靶点较少，而且这种疾病对微管抑制剂药物不敏感或迅速产生耐药性是出了名的。我们已经为CRC确定了一个合适但新兴的目标，与我们的技术非常匹配，我们需要围绕破坏DNA的有效载荷创新和发展我们的专业知识。这个发现和早期开发项目旨在发现一组抗体片段(使用我们为FDC优化的专有库)，并合成与我们更小、更具穿透力的格式兼容的接头有效负载衍生品。我们已经实施了发现战略，并获得了一些有希望的候选抗体的初步数据，我们需要扩大这一战略，以有更广泛的选择范围。我们也有初步的化学数据，这个项目以此为基础来完善合成，并发现一些潜在的新颖和可申请专利的新接头-有效载荷新的有效载荷将与新的抗体片段结合，创建用于CRC治疗的新颖和专有的FDDC。使用我们已建立的流程，我们将使用我们的一套生物物理分析技术和生物检测来充分表征候选的FDCs，旨在产生动物模型的早期概念验证。在成功之后，将进一步投资开发先进型号的领先产品，并最终用第二种创新和急需的固体肿瘤治疗产品填充安提科的生产线。

Antikor Biopharma is pioneering an innovative drug delivery platform called OptiLink, tailored for solid tumours. It is unique by utilising specially-engineered, small-format, tumour-specific antibodies with appropriately-designed linkers to specifically deliver potent cytotoxic payloads deep into tumours. Unlike its competitors, who use full-size antibody-drug conjugates (ADCs), Antikor's technology enables much smaller fragment-drug conjugates (FDCs) to be developed. These have many advantages: FDC products potentially have a higher therapeutic index for cancer therapy as they are more potent, can be dosed more aggressively because they clear from normal tissues more quickly and penetrate rapidly and deeply into tumours enabling faster and more effective tumour destruction.Through previous Innovate-UK support, Antikor expanded and refined its technology and discovered a strong pre-clinical FDC candidate (ANT-045) aimed at gastric cancer which is now entering formal IND-enabling studies with expectations for a regulatory filing in 18 months.Antikor is now expanding its pipeline to another difficult-to-treat solid tumour, colorectal cancer (CRC). Although gastrointestinal in nature, this has very different challenges to gastric. There are fewer well-characterised targets for CRC and this disease is notoriously insensitive or rapidly-develops resistance to microtubule inhibitor drugs. We have identified a suitable but emerging target for CRC, well- matched to our technology and we need to innovate and develop our expertise around DNA-damaging payloads. This discovery and early development project aims to discover a panel of antibody fragments (using our proprietary libraries optimised for FDCs) and to synthesize linker-payload derivatives that are compatible with our smaller, more penetrating format.We have already implemented the discovery strategy and have preliminary data on some promising candidates and we need to expand this to have a wider range to choose from. We also have preliminary chemistry data and this project builds on this to refine the synthesis and discover some potentially novel and patentable new linker-payloadsNew payloads will be conjugated to new antibody fragments to create novel and proprietary FDCs for CRC therapy. Using our established process, we will use our suite of biophysical analytical techniques and biological assays to fully-characterise candidate FDCs, aiming to generate early proof-of-concept in animal models. Success will be followed by further investment to develop leads in advanced models and ultimately fill Antikor's pipeline with a second innovate and much- needed product for solid tumour therapy.