编者按：近年来，癌症药物研发的重心正悄然发生转变。与过去围绕成熟靶点持续进行优化迭代不同，新一轮创新更加聚焦于 如何突破长期被视为"不可成药"（undruggable）的靶点。在2025年欧洲肿瘤内科学会（ESMO）靶向抗癌治疗（TAT）大会 上，多项针对此类靶点的创新疗法首次人体研究结果相继公布，显示该领域正加速从基础探索迈向临床验证阶段。随后， Annals of Oncology对其中具有代表性的研究进行了系统梳理，重点介绍了已在人体中完成机制验证、展现出生物标志物相关信 号且具有可控安全性的候选药物，同时也涵盖多项仍处于临床前阶段、但有望突破"不可成药"限制的创新技术平台。 作为全球医药创新的赋能者，药明康德依托一体化、端到端的CRDMO平台，持续支持全球合作伙伴加速创新疗法研发进程， 致力于将更多突破性治疗方案带给癌症患者。本文将基于Annals of Oncology的相关内容，并结合公开资料，梳理当前"不可成 药"靶点领域涌现的早期突破及其潜在意义，呈现这一前沿方向的最新发展脉络。 靶点：MYC MYC长期被认为属于典型的"不可成药"靶点。其蛋白结构高度动态且缺乏稳定结合口袋，使传统小分子难以实 ...

Company Overview - Lingke Pharmaceutical (Zhejiang) Co., Ltd. has submitted an application for listing on the Hong Kong Stock Exchange, with CITIC Securities and Jianyin International as joint sponsors [1] - The company is a leading developer of innovative differentiated small molecule inhibitors targeting autoimmune and inflammatory diseases, focusing on the JAK-STAT signaling pathway [3] Product Pipeline - Key products include LNK01001, a highly selective second-generation JAK1 inhibitor, and LNK01004, a potential first-in-class third-generation soft pan-JAK inhibitor, both targeting autoimmune and inflammatory diseases [3] - LNK01006 is a cutting-edge, highly selective allosteric TYK2 inhibitor designed to penetrate the central nervous system, targeting related diseases [3] - The company has developed the proprietary IsoNova protein degradation platform, which enhances target selectivity and reduces off-target effects, expanding the range of degradable targets [3][4] Market Potential - The global JAK inhibitor market is projected to grow from $5.5 billion in 2019 to $13.9 billion in 2024, with expectations to reach $25.6 billion by 2028 and $40.8 billion by 2033 [6][16] - In China, the JAK inhibitor market is expected to expand from RMB 400 million in 2019 to RMB 3.8 billion in 2024, with forecasts of RMB 17.1 billion by 2028 and RMB 46.5 billion by 2033 [6][16] Clinical Development - As of the last feasible date, the company has 53 issued patents and 106 pending patent applications, with 34 issued patents and 45 pending applications related to its core and key products [7] - LNK01001 is currently undergoing multiple Phase III clinical trials, with new drug application stages expected in 2026 and 2027 for various indications [7] - LNK01004 has completed Phase II trials in China and plans to initiate Phase III trials in mid-2027 [7] Financial Performance - The company reported other income of RMB 20.57 million in 2023, RMB 16.98 million in 2024, and RMB 54.78 million for the nine months ending September 30, 2025 [9] - Annual losses were approximately RMB 260 million in 2023, RMB 312 million in 2024, and RMB 145 million for the nine months ending September 30, 2025 [10] - Research and development expenses were RMB 186 million in 2023, RMB 223 million in 2024, and RMB 121 million for the nine months ending September 30, 2025 [11] Industry Overview - The global market for autoimmune and inflammatory disease drugs grew from $133 billion in 2019 to $160.8 billion in 2024, with a compound annual growth rate (CAGR) of 3.9% [13] - The Chinese market for autoimmune and inflammatory disease drugs is expected to grow from RMB 42.7 billion in 2019 to RMB 66.5 billion in 2024, with a CAGR of 9.3% [13][14]

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