Harnessing FDC technology for metastatic colorectal cancer (mCRC)

Antikor Biofilma正在开创一种名为OptiLink的创新药物输送平台，专为实体瘤量身定制。其独特之处在于利用专门工程化的小规格肿瘤特异性抗体与适当设计的接头，将强效细胞毒性有效载荷特异性递送至肿瘤深处。与使用全尺寸抗体药物缀合物（ADC）的竞争对手不同，Antikor的技术能够开发更小的片段药物缀合物（FDC）。这些有许多优点：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，因为它们可以更快地从正常组织中清除，并快速深入地渗透到肿瘤中，从而更快，更有效地破坏肿瘤。通过之前的Innovate-UK支持，Antikor扩展并完善了其技术，发现了一种针对胃癌的强有力的临床前FDC候选药物（ANT-045），目前正在进入正式的IND-Antikor目前正在将其产品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的，但这对胃有非常不同的挑战。CRC的明确靶点较少，并且这种疾病对微管抑制剂药物不敏感或迅速产生耐药性。我们已经确定了一个合适的，但新兴的目标，为CRC，以及匹配我们的技术，我们需要创新和发展我们的专业知识，围绕DNA损伤的有效载荷。这个发现和早期开发项目旨在发现一组抗体片段（使用我们针对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-有效载荷衍生物。我们已经实施了发现策略，并获得了一些有希望的候选物的初步数据，我们需要扩大这一范围，以提供更广泛的选择。我们也有初步的化学数据，这个项目建立在此基础上，以完善合成，并发现一些潜在的新的和专利的新的接头payloads新的有效载荷将结合到新的抗体片段，以创造新的和专有的FDC的CRC治疗。使用我们建立的过程，我们将使用我们的一套生物物理分析技术和生物测定来完全验证候选FDC，旨在在动物模型中产生早期概念验证。成功之后，将进一步投资，以开发先进模型的领先优势，并最终填补安提科的管道与第二个创新和急需的产品，为实体肿瘤治疗。

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.