2021年6月18日(美国时间), Ambrx于美国纽约证券交易所挂牌上市，受到了行业广泛关注。其独特的ADC偶联技术是原因之一。Ambrx的技术平台能将合成氨基酸（SAA）整合到活细胞中的蛋白中，以克服传统的基于天然氨基酸偶联方法的局限，从而开发出精准设计的生物药物。
基于此，本次第九届国际生物药大会Biocon-Antibody 2022（3月22-23日，上海宝华万豪酒店）非常有幸能够邀请到Ambrx研发运营高级副总裁和中国地区总负责人张韶辉博士，并请张博在会前先行分享一些他和团队在ADC药物开发领域的心得与经验。作为一位药物靶点选择和验证、试验开发、先导物发现、临床前和临床开发方面具有实践和管理经验的专家，张博也将在会上从Ambrx非天然氨基酸技术的定点偶联优化设计ADC的稳定性与有效性方向做专题报告。
Dr. Shawn Zhang has served as our Senior Vice President of R&D Operations and Ambrx China since April 2021, and previously was Vice President of Research. Dr. Zhang is an established executive in the areas of drug R&D, business development, product sourcing, in-licensing, project management and senior management leadership. Shawn has also demonstrated hands-on and managerial experience in drug target selection and validation, assay development, lead discovery, preclinical and clinical development. Before his appointment, Shawn was the Vice President of Research at HUYA Bioscience International. As a senior management team member, he oversaw new product sourcing, drug evaluation, in-licensing, and research/ development, in a wide range of therapeutic areas including oncology, metabolic diseases, inflammation and companion diagnostics/biomarkers. Prior to that, in Mitsubishi-Tanabe, Shawn established and led multiple drug projects in oncology, immunology and metabolic diseases. Dr. Zhang performed his postdoctoral training at Cold Spring Harbor Laboratory, obtained his Ph.D. in Biochemistry from UCSD/Salk Institute, MS in molecular genetics from Institute of Genetics, Chinese Academy of Science and B.S. in biology from Beijing Normal University.
BioCon组委：ADC 发展突飞猛进，您作为药物研发等多领域的专家，首先想请您从您的角度谈谈，您认为现在中国和国际在ADC药物研发上存在哪些挑战，以及潜在的解决思路？
张博：
原文：
The main issue has always been ADC stability. Most ADC will loose payloads during circulation in the body. Technology has been evolving in improving the stability of linker and conjugation chemistry.
MOA of payloads needs diversity as cell will develop mechanism to acquire drug resistance.
ADC的稳定性一直是主要问题，ADC会在体内循环过程中减少有效载荷。
新的技术一直是围绕着如何提高链接子和偶联化学（linker & conjugation chemistry）的稳定性。可控的定点偶联及血清中稳定的化学是问题的关键。
另外，我认为需要提高小分子化药毒物部分（payload）作用机制的多样性，因为细胞总会产生抗性机制。
BioCon组委：据了解，Ambrx 开创了世界上第一个在细胞内将非天然氨基酸定点整合到蛋白质肽链上的技术平台，请您谈谈该平台对于生物药研发而言有怎样的助力？目前团队的最新进展如何？
张博：
原文：
Yes, Ambrx pioneered the first syntheticamino acid (SAA) incorporation into proteins in a living cell.
Protein engineering by chemical modification needs to be precise modification. Traditional conjugation technologies are mostly based on cysteine and lysine, which existing in multiple sites of each protein, it will be hard to do chemical conjugation at a single site, leading to a mixture of different DAR. Ambrx can incorporate a single SAA into a protein, then using specific chemistry to stably conjugate the chemical payload to the SAA, producing a single uniform product.
Ambrx technology can perform systemic SAR on a protein to incorporate SAA to modify the protein, other technologies currently are hard to do so.
是的，Ambrx是第一个将非天然氨基酸或叫合成氨基酸（SAA，NNAA)掺入活细胞蛋白质的先驱。
为了保持或设计蛋白质的精准生物功能，蛋白质的化学修饰需要精确设计和可控性。
传统的偶联技术大多基于半胱氨酸和赖氨酸，它们存在于每个蛋白质的多个位点上，很难在单个位点上进行化学偶联，导致不同DAR的混合。 而Ambrx可以将单个SAA结合到蛋白质中，然后使用特定的化学方法将有效载荷稳定地偶联到SAA上，产生均一的偶联产物。
Ambrx技术使得对蛋白质进行系统性的结构活性关系(SAR)的研究成为可能。这样可以沿着蛋白肽链选择任何一个位点利用掺入SAA，然后对蛋白质进行精准的化学修饰，这是目前其他技术难以做到的。
BioCon组委：您在Ambrx 负责运营等工作，也想请您简单分享下接下来Ambrx在ADC领域的布局与开发战略？如何推进现有的管线？
张博：
原文：
Ambrx currently has 3 ADC in clinical trials or to be entered into clinical trials
ARXARX788, HER2 ADC, is positioned to breast cancer, gastric cancer and some other HER2 expression cancers. Currently at different stages (Phase 1-3) of clinical development.
517, PSMA ADC, is initially focused on prostate cancer, currently in a Phase 1 clinical trial.
ARX305, CD70 ADC, is just cleared IND in the US FDA, targeting multiple solid tumors.
Ambrx目前有3个ADC处于临床试验或即将进入临床试验：
第一个是ARX788，即HER2 ADC，定位于乳腺癌、胃癌和其他一些HER2表达的癌症。 目前处于临床开发的不同阶段(1-3期)。
第二个是ARX517, PSMA ADC，最初专注于前列腺癌，目前处于1期临床试验。
第三个是ARX305, CD70 ADC，是美国FDA刚刚批准的针对多种实体肿瘤的IND。
BPC组委：非常感谢张博士的精彩分享！敬请期待张博士在 BioCon 会议现场带来更多关于创新偶联药物的分享！
新靶点/机制/Biology/分子设计/ADC及其他偶联药物/单/双多抗/…等创新抗体药物探索，尽在BioCon-Antibody2022！