Adagrasib

SAN DIEGO--( BUSINESS WIRE )--Iambic Therapeutics, a clinical-stage biotechnology company developing novel therapeutics using its unique AI-driven discovery platform, today announced the appointment of Peter Olson, Ph.D. to the role of chief scientific officer. Dr. Olson, who was most recently vice president, research at Mirati Therapeutics, a Bristol Myers Squibb (BMS) company, will join Iambic’s executive leadership team. A specialist in cancer biology and genetics, Dr. Olson will lead a team focused on driving small molecule programs from target identification through to clinical proof-of-concept. At Mirati, he led in vitro and in vivo pharmacology and translational research across its portfolio, which included pre-clinical efforts for KRAZATI™ (adagrasib), a KRAS G12C inhibitor approved by the US Food and Drug Administration (FDA) in 2022. “We couldn’t be more excited to welcome Pete Olson to the Iambic team,” said Tom Miller, PhD, Iambic’s chief executive officer. “He brings extraordinary drug discovery and development leadership experience as we advance and expand our pipeline of clinical candidates for oncology and other disease areas.” Iambic is developing an internal pipeline of candidates, discovered using its platform that integrates AI models for protein structure prediction and wholistic drug design with high-throughput chemistry and biology experimentation. The Company’s pipeline currently includes IAM1363, a highly selective, brain penetrant small molecule inhibitor of both wild-type and oncogenic HER2 mutants currently in a Phase 1/1b study, as well as a potential first-in-class selective dual CDK2/4 inhibitor for multiple cancer indications, an allosteric inhibitor for KIF18A, and additional new programs. “Iambic’s AI-driven discovery platform enables the rapid identification of promising drug molecules and provides predictive insights into clinical properties of potential medicines,” said Dr. Olson. “I am excited to join the Iambic team to further advance their promising pipeline as we work to deliver innovative breakthroughs for patients.” Dr. Olson has over twenty-five years of basic, pre-clinical and translational cancer biology experience in academia and industry and is the author of close to 50 peer-reviewed papers. Prior to Mirati he was a senior principal scientist in Pfizer’s Oncology Research Unit, where he was the translational project leader for OGSIVEO™, the first FDA approved treatment for progressive desmoid tumors. Before Pfizer, he was a postdoc in the Hanahan Laboratory at the University of California, San Francisco. He received his Ph.D. in Biology from the University of California, San Diego and a B.S. in Biochemistry from the University of California, Davis. About Iambic’s AI-Driven Discovery Platform The Iambic AI-driven platform was created to address the most challenging design problems in drug discovery, leveraging technology innovations such as Enchant, a multi-modal transformer model that predicts clinical outcomes from the earliest stages of discovery, and NeuralPLexer, the best-in-class predictor of protein and protein-ligand structures. The integration of physics principles into the platform’s AI architectures improves data efficiency and allows molecular models to venture widely across the space of possible chemical structures. The platform enables identification of novel chemical modalities for engaging difficult-to-address biological targets, discovery of defined product profiles that optimize therapeutic window, and multi-parameter optimization for highly differentiated development candidates. Through close integration of AI-generated molecular designs with automated experimental execution, Iambic completes design-make-test cycles on a weekly cadence. About Iambic Therapeutics Founded in 2019 and headquartered in San Diego, California, Iambic Therapeutics is disrupting the therapeutics landscape with its unique AI-driven drug-discovery platform. Iambic has assembled a world-class team that unites pioneering AI experts and experienced drug hunters with strong track records of success in delivering clinically validated therapeutics. The Iambic platform has been demonstrated to deliver high-quality, differentiated therapeutics to clinical stage with unprecedented speed and across multiple target classes and mechanisms of action. The Iambic team is advancing an internal pipeline of clinical assets to address urgent unmet patient needs. Learn more about the Iambic team, platform, and pipeline at iambic.ai .

来源：药渡 撰文：万有引力     编辑：维他命 近日（2024年12月6日），CDE（国家药品监督管理局药品审评中心）官网显示百济神州自主研发的1类新药BGB-53038正式获批进入临床阶段，拟用于治疗晚期实体瘤患者。 BGB-53038作为一款Pan-KRAS抑制剂，这是该药在国内首次获得临床批件，标志着百济神州在抗癌药物研发领域取得了又一重要突破。 图1. BGB-53038获批进入临床阶段，来源：CDE官网 1 研发背景 KRAS，即Kirsten大鼠肉瘤病毒癌基因同源物，是一种广泛存在于多种肿瘤突变中的关键基因。研究表明，约23%-25%的癌症患者携带有KRAS突变，这些突变类型多样，包括G12C、G12D、G12R、G12A等。KRAS突变导致细胞无法控制地生长和分裂，进而引发肿瘤。然而，长期以来，KRAS一直被视为“不可成药”的靶点，因为其结构复杂且高度动态，难以被药物有效抑制。 图2. KRAS-G12C抑制剂作用机制示意图 近年来，随着生物技术和药物研发的不断进步，KRAS抑制剂的研发取得了突破性进展。2021年，安进公司的KRAS抑制剂索托拉西布开出首张处方，标志着KRAS抑制剂正式进入临床应用。然而，目前全球已上市的KRAS抑制剂仅有4款，且均为针对KRAS G12C突变的抑制剂。尽管这些药物在一定程度上改善了KRAS G12C突变患者的预后，但仍存在较大的尚未满足的临床需求。 今年9月，百济神州启动了BGB-53038首次人体I期研究（NCT06585488），旨在评估其作为单药治疗携带KRAS突变或扩增的晚期或转移性实体肿瘤患者的安全性、耐受性、药代动力学（PK）、药效学和初步抗肿瘤活性。同时，该研究还探索了BGB-53038与替雷利珠单抗联合用于非鳞状非小细胞肺癌（NSCLC）患者，以及与西妥昔单抗联合用于结直肠癌（CRC）患者的疗效。 2 Pan-KRAS抑制剂机理和特点 BGB-53038为一款高度选择性的pan-KRAS抑制剂，对NRAS、HRAS的抑制活性很弱，其独特的作用机制为肿瘤治疗提供了新的思路。与其他pan-KRAS抑制剂不同，BGB-53038高度选择性地作用于KRAS，对NRAS和HRAS的影响较小，这使得它在治疗肿瘤时能够更加精准地针对KRAS突变，减少对其他相关蛋白的不必要抑制，从而降低潜在的副作用风险。 这种高度选择性的作用机制为肿瘤治疗带来了新的可能性。例如，在治疗晚期实体瘤时，BGB-53038可以更有效地抑制肿瘤细胞的生长和扩散，同时减少对正常细胞的损害。此外，由于其对NRAS和HRAS的抑制活性很弱，BGB-53038可能与其他针对不同靶点的肿瘤治疗药物联合使用，发挥协同作用，提高治疗效果。 与Revolution Medicines、加科思、礼来等公司的pan-KRAS抑制剂相比，BGB-53038的独特作用机制使其在竞争激烈的研发领域中脱颖而出。这些公司的抑制剂在作用机制上可能存在一些差异，但都致力于攻克KRAS突变这一难题。BGB-53038 的高度选择性为其在临床应用中提供了优势，有望为晚期实体瘤患者带来更好的治疗选择。 3 Pan-KRAS抑制剂疗效和安全性 BGB-53038的临床研究数据为其疗效和安全性提供了有力证据。在首次人体I期研究中，BGB-53038展现出了良好的安全性和耐受性。研究结果显示，多数患者能够耐受BGB-53038的治疗，且未出现严重的不良反应。同时，BGB-53038还初步展现出了抗肿瘤活性，部分患者的肿瘤负荷得到了有效控制。 在与其他靶向药物联用的研究中，BGB-53038也展现出了良好的协同作用。 与替雷利珠单抗联合用于非鳞状非小细胞肺癌（NSCLC）患者的研究结果显示，联合治疗组患者的肿瘤缓解率和生存期均优于单药治疗组。 同样，与西妥昔单抗联合用于结直肠癌（CRC）患者的研究也取得了积极结果。 这些研究结果为BGB-53038的未来临床应用提供了有力支持。 此外，BGB-53038的药代动力学（PK）和药效学（PD）研究结果也为其疗效和安全性提供了重要依据。研究结果显示，BGB-53038在体内具有良好的药代动力学特性，药物浓度稳定且持续时间长。同时，BGB-53038还能够有效抑制KRAS突变蛋白的活性，从而阻断细胞信号传导，抑制肿瘤细胞的生长和分裂。这些研究结果为BGB-53038的临床应用提供了科学依据和理论支持。 4 Pan-KRAS抑制剂市场价值 Pan-KRAS抑制剂的市场价值不可小觑。目前，全球范围内在研的Pan-KRAS抑制剂近35款，其中进入临床阶段的有7款。这些药物的研发不仅为患者提供了更多治疗选择，也为医药市场带来了巨大的商业价值。 从市场份额来看，KRAS突变患者数量庞大，且目前市场上已上市的KRAS抑制剂种类有限，因此Pan-KRAS抑制剂的市场潜力巨大。据估计，仅KRAS G12C和KRAS G12D就将是一个约超100亿美元的市场。从覆盖群体来看，Pan-KRAS突变可以覆盖多个瘤种，全球每年有270万患者携带KRAS突变，其市场价值大约是KRAS G12C 抑制剂的8倍左右。 目前已有多款KRAS抑制剂进入临床阶段或已上市。其中，安进公司的索托拉西布和Mirati公司的阿达格拉西布是两款具有代表性的KRAS G12C抑制剂。这两款药物在市场上取得了不错的销售业绩，但也面临着耐药性和适用范围有限等问题。相比之下，Pan-KRAS抑制剂具有更广泛的适用范围和更好的联用效果，因此具有更大的市场潜力。 在国内市场方面，加科思和璎黎药业等创新药企已将Pan-KRAS抑制剂推进至临床阶段，辉瑞等跨国药企也在积极布局这一领域。随着国内医药产业的快速发展和创新能力的提升，未来国内Pan-KRAS抑制剂市场有望迎来爆发式增长。随着医药市场的不断扩大和竞争的加剧，Pan-KRAS抑制剂的市场竞争也将更加激烈。因此，百济神州等创新药企需要不断加强研发创新和市场拓展能力，以在激烈的市场竞争中脱颖而出。 结 语 百济神州Pan-KRAS抑制剂BGB-53038的临床获批标志着公司在抗癌药物研发领域取得了又一重要突破。BGB-53038作为一款具有广泛适用范围和良好疗效的Pan-KRAS抑制剂，为患者提供了新的治疗选择。随着研究的深入和临床应用的推广，BGB-53038有望在未来成为抗癌药物市场的重要力量。 参考资料： 1. CDE官网 2. 百济神州公司官网 *声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！ 盘点：11月FDA批准上市的重磅药物 10亿美金！映恩生物新型ADC药物独家授权GSK MNC加速扫货中国创新药，狂掀“买买买”热潮！