Zirdafulven

写在前面 传统新药研发有多难？ 平均投入26亿美元，耗时12–15年，临床试验成功率不足10%。这组数字背后，是整个制药行业长期面临的投入高、周期长、失败率高的三重困境。 而人工智能，正在从根本上重塑这一格局。 这篇发表于药物化学顶刊JMC的编辑部综述，系统梳理了AI在药物研发全生命周期中的落地应用——从最上游的靶点识别，到虚拟筛选、分子设计、ADMET评价，再到临床试验优化、老药新用，乃至上市后的安全监测。文章不仅讲清了技术逻辑，还附上了27款已进入临床阶段的AI研发药物清单，是目前AI制药领域最全面的全景式综述之一。 下面我们按照药物研发的经典流水线，逐阶段拆解AI的价值与真实案例。一、靶点识别：从大海捞针到精准定位 靶点是新药研发的起点。找到真正驱动疾病的关键蛋白/基因，后续所有工作才有意义。传统方法的瓶颈 传统靶点发现依赖全基因组敲除筛选、亲和下拉实验等湿实验手段：周期长、失败率高、难以挖掘复杂疾病网络中的隐藏关键节点。AI如何破局 AI通过整合多维度生物数据，从假设驱动转向数据驱动的靶点发现：多组学数据建模、图深度学习、知识图谱、生物大语言模型。经典案例 INS018-055（特发性肺纤维化，II期临床）：由英矽智能PandaOmics平台发现。AI通过整合多组学数据与生物网络分析，锁定TNIK激酶为纤维化治疗新靶点，并基于此设计出特异性抑制剂。二、虚拟筛选：百万级化合物库的计算机初筛 靶点确定后，下一步是从数十万乃至上百万个化合物中，找出能与靶点结合的活性分子。两类经典筛选范式 基于结构的虚拟筛选（SBVS）和基于配体的虚拟筛选（LBVS）。AI带来的技术升级 等变神经网络对接模型、配体-受体共折叠模型（AlphaFold3、RosettaFold）、结合姿态智能优化。经典案例 NDI-034858（斑块型银屑病，III期临床）：又名Zasocitinib（TAK-279），是一款高选择性TYK2抑制剂。三、分子生成：AI从零设计全新化学骨架 如果说虚拟筛选是从已有库中找，那么生成式AI就是无中生有造新分子。AI生成式设计的核心技术 强化学习（RL）、变分自编码器（VAE）、生成对抗网络（GAN）。现状与挑战 AI生成分子目前最大的痛点是合成可行性——很多纸上完美的分子，实际合成难度极大。四、ADMET评价：临床前的安全守门员 ADMET是决定一个分子能否成药的关键。据统计，超过半数的临床失败，根源都在于ADMET性质不佳。ADMET五个维度 A - 吸收（Absorption）、D - 分布（Distribution）、M - 代谢（Metabolism）、E - 排泄（Excretion）、T - 毒性（Toxicity）。AI ADMET预测方案 传统机器学习、深度神经网络（DNN）、几何图神经网络（GeoGNN）。图1：AI在药物研发各阶段的应用全景 下图完整展示了AI从靶点识别到上市后监测的全链条布局，建议收藏。 图注：AI技术贯穿药物研发六大核心阶段——靶点识别、药物发现、临床前开发、临床试验、药品获批、上市后监测，每个阶段均有对应的AI应用场景。五、生物标志物：精准医疗的核心标尺 生物标志物是连接药物与患者的桥梁，分为诊断标志物、预后标志物、疗效预测标志物三类。AI在标志物领域的应用 数字病理诊断（如nuclei.io平台）、细胞形态标志物、蛋白组标志物。六、药物重定位：老药新用，AI制药最快落地赛道 药物重定位（Drug Repurposing），就是为已经上市、安全性已验证的老药，找到全新的治疗适应症。AI三大实现路径 组学特征匹配、真实世界数据挖掘、知识图谱推理。经典案例 PXT3003（腓骨肌萎缩症1A型，III期临床）：由Pharnext公司通过AI辅助重定位发现。七、临床试验：AI提升人体试验成功率 AI从患者招募、试验设计、剂量优化等多个维度切入，降低临床风险。AI的四大核心价值 精准患者筛选、试验结局预测、治疗窗口优化、患者招募加速。八、上市后监测：AI守护全生命周期用药安全 药物获批上市不是终点，而是长期安全监测的起点。监管端的AI实践（以FDA为例） 自动分类不良事件报告、NLP文本挖掘（InfoViP平台）、持续风险监控。表1：代表性AI研发药物临床管线一览 下表汇总了27款已进入各阶段临床试验的AI赋能药物，涵盖肿瘤、自身免疫、神经、罕见病等多个治疗领域。 药物编号 药物名称 研发公司 适应症 临床阶段 NCT编号 1 PXT3003 Pharnext 腓骨肌萎缩症1A型 III期 NCT03023540 2 BTRX-335140 Neumora 重度抑郁症 III期 NCT06058013 3 NDI-034858 武田制药 斑块型银屑病 III期 NCT06973291 4 REC-2282 Recursion 2型神经纤维瘤病 II/III期 NCT05130866 5 HLX-0201 Healx 男性脆性X综合征 II期 NCT04823052 6 LAM-001 Steven Hays 闭塞性细支气管炎综合征 II期 NCT06018766 7 LAM-002A OrphAI Therapeutics 肌萎缩侧索硬化 II期 NCT05163886 8 SOM0226 SOM Innovation Biotech 转甲状腺素蛋白淀粉样变性 II期 NCT02191826 9 SOM3355 SOM Innovation Biotech 亨廷顿病舞蹈症 II期 NCT05475483 10 LP-100 Allarity 转移性去势抵抗性前列腺癌 II期 NCT03643107 11 LP-300 Lantern Pharma 晚期肺腺癌 II期 NCT05456256 12 REC-994 Recursion 脑海绵状血管畸形 II期 NCT05085561 13 BT-11 NImmune 溃疡性结肠炎 II期 NCT03861143 14 INS018-055 英矽智能 特发性肺纤维化 II期 NCT05975983 15 NDI-1150-101 Nimbus 实体瘤 I/II期 NCT05128487 16 ERAS-007 Erasca 晚期胃肠道恶性肿瘤 I/II期 NCT05039177 17 REC-4881 Recursion 家族性腺瘤性息肉病 I/II期 NCT05552755 18 LP-184 Lantern 实体瘤 I/II期 NCT05933265 19 BXCL701 BioXcel Therapeutics 转移性去势抵抗性前列腺癌 I/II期 NCT03910660 20 RLY-4008 Elevar Therapeutics 实体瘤 I/II期 NCT04526106 21 SGR-1505 Schrdinger 复发/难治性B细胞淋巴瘤 I期 NCT05544019 22 NX-13 Landos Biopharma 溃疡性结肠炎 I期 NCT04862741 23 BXCL-501 BioXcel Therapeutics 儿童精神分裂症与双相情感障碍相关躁动 I期 NCT05025605 24 PHI-101 首尔国立大学医院 急性髓系白血病 I期 NCT04842370 25 BPM-31543 BPGbio 脱发 I期 NCT01588522 26 RLY-1971 罗氏 转移性实体瘤 I期 NCT04252339 27 RLY-2608 Relay Therapeutics 晚期实体瘤或乳腺癌 I期 NCT05216432 数据来源：clinicaltrials.gov，截至2025年10月九、挑战与局限：AI不是万能钥匙 文章没有神化AI，而是客观指出了当前行业面临的核心问题： 1. 高质量训练数据稀缺：生物医学数据量少、标注难，且大量阴性实验数据从未公开。 2. 生成分子的合成可行性问题：很多AI生成的全新骨架，实际合成难度大。 3. 不可成药靶点仍是难题：转录因子、支架蛋白等柔性强、无明确结合口袋的靶点。 4. 黑箱问题阻碍监管信任：深度学习模型决策过程不透明。 5. 监管政策尚未完善：FDA等机构仍在制定AI药物研发的明确指导原则。十、未来展望 针对上述挑战，文章提出了几个关键发展方向： 数据标准化与共享：建立统一的生物医药数据标准，推动阴性数据公开。 多模态融合：结合化学结构、文本、组学等多模态信息，缓解数据不足问题。 虚拟人体仿真：构建数字孪生患者模型，模拟疾病机制与药物作用。 罕见病药物开发：通过AI老药重定位，为孤儿病快速找到治疗方案。 监管体系完善：建立AI模型可解释性标准，明确申报路径。总结 AI正在从一个锦上添花的工具，逐步变为药物研发各环节的标配能力。 从靶点发现的源头创新，到虚拟筛选的效率提升，从ADMET的早期风险把控，到临床试验的成功率优化，再到上市后的安全监测——AI正在重构整条药物研发流水线。 如今已有数十款AI发现/优化的药物进入临床，其中多款推进至III期。虽然数据质量、合成可行性、监管规范等问题仍待解决，但AI重塑制药行业的大趋势已经不可逆转。 对于从业者而言，理解AI、用好AI，将成为未来药物研发人员的核心能力之一。

The FDA raised no objections to Lantern's key proposed protocol amendments to the HARMONIC™ clinical trial. Amendments include: (1) enriching enrollment for patients with EGFR exon 21 L858R mutations; (2) extending LP-300 dosing to a maximum of eight cycles; and (3) transitioning to a single-arm study design — changes that align with emerging data and support a clearer regulatory and partnering path. EGFR exon 21 L858R mutations account for approximately 40% of all EGFR-mutant NSCLC globally and up to 50% in Asian populations — a molecularly defined subset that consistently experiences inferior outcomes when treated with current EGFR-targeted therapies relative to patients with exon 19 deletions. DALLAS--(BUSINESS WIRE)--Lantern Pharma Inc. (NASDAQ: LTRN), a clinical-stage, AI-driven precision oncology company, today announced that it has received a successful response to its recent Type C meeting request from the U.S. Food and Drug Administration (FDA), focused on the ongoing Phase 2 HARMONIC™ trial of LP-300 in never-smokers with advanced non-small cell lung cancer (NSCLC) adenocarcinoma. In its written responses to Lantern's Type C meeting request, the FDA raised no objections to key proposed protocol amendments, providing a more focused, clearer regulatory path forward for the HARMONIC™ trial and for the future development of LP-300 in this distinct, high-need patient population. The HARMONIC™ trial is designed to evaluate LP-300, a small molecule given in combination with carboplatin and pemetrexed, in never-smokers with advanced NSCLC adenocarcinoma who have experienced disease progression following treatment with kinase inhibitors. Never-smoker NSCLC is increasingly recognized as a distinct disease entity with unique clinical and genomic features. Globally, approximately 400,000 to 500,000 patients are diagnosed with never-smoker NSCLC each year — a patient population that, if classified separately, would rank among the most common cancers worldwide. Despite this scale, no therapies have been specifically developed or labeled for the never-smoker NSCLC patient population, and the EGFR exon 21 L858R subset in particular continues to experience inferior outcomes when treated with currently available standards of care. “In our view, this successful Type C interaction with the FDA is a meaningful de-risking milestone for the LP-300 program and for the HARMONIC™ trial. The FDA's response to our proposed amendments supports our strategy to focus HARMONIC™ on the EGFR exon 21 L858R-mutant never-smoker population, where emerging data suggest LP-300 may offer meaningful differentiated benefit when added to standard chemotherapy following TKI failure.” — Panna Sharma, President and Chief Executive Officer, Lantern Pharma Inc. Focused Enrollment in EGFR Exon 21 L858R Never-Smokers Under the amended protocol supported by the FDA's Type C responses, Lantern plans to focus all future HARMONIC™ enrollment on patients harboring the EGFR exon 21 L858R mutation, a subtype of EGFR kinase domain mutations associated with lower TKI binding affinity and inferior outcomes on osimertinib-based therapy relative to patients with exon 19 deletions. Preliminary analyses from the ongoing HARMONIC™ trial suggest that patients with EGFR exon 21 L858R-mutant disease may derive greater clinical benefit from the LP-300 triplet regimen than other EGFR-mutant subgroups, providing a biologically and clinically compelling rationale to enrich the study for this population. Based on currently available data, preliminary multivariable Cox regression analyses incorporating race, gender, and TP53 mutation status have confirmed L858R as an independent predictor of progression-free survival benefit in the trial, suggesting the signal is not driven by demographic confounders. “The preliminary signal in the EGFR exon 21 L858R cohort — including a median progression-free survival of 8.3 months and durable responses extending beyond two years in select patients — gives us confidence that an enriched, single-arm design is the right next step. Aligning the trial with that signal, and receiving no objection from the FDA to key aspects of our approach via a successful Type C interaction, positions us to generate a more focused, decision-enabling data-set for patients, regulators, and potential partners.” — Panna Sharma, President and Chief Executive Officer, Lantern Pharma Inc. Extended LP-300 Dosing Based on Safety and Emerging Outcomes In addition to refining the molecularly defined patient population, the Type C feedback supports Lantern's proposal to increase the maximum number of LP-300 treatment cycles in HARMONIC™ from six to eight. This change is supported by historical safety data from prior clinical experience with LP-300 indicating that up to eight cycles at the current dose level did not alter the established safety pro the drug, as well as by emerging HARMONIC™ data suggesting improved outcomes with longer LP-300 treatment duration. By extending LP-300 dosing, Lantern aims to maximize the depth and durability of response without adding clinically meaningful toxicity beyond that expected with carboplatin and pemetrexed alone. In earlier studies, LP-300 has been administered in multiple clinical trials to more than 1,000 individuals and has generally been well tolerated, providing a substantial safety foundation for this dosing adjustment. Transition to a Single-Arm, Enriched Study Design As part of the protocol amendments proposed in the Type C meeting interaction, Lantern will discontinue enrollment into the control arm of the HARMONIC™ trial and migrate the study into a single-arm design that only enrolls additional patients with the EGFR exon 21 L858R mutation. This evolution reflects the rapidly changing treatment landscape in TKI-refractory NSCLC, where increasing availability of subsequent-line therapies and patient preferences have made continued randomization to a traditional chemo-doublet control arm operationally challenging in never-smokers. The enriched, single-arm design is intended to accelerate enrollment, sharpen the clinical signal within a genomically defined subgroup, and enable more efficient comparisons to historical and real-world benchmarks in EGFR exon 21 L858R-mutant never-smoker NSCLC. Lantern anticipates that the amended design, coupled with continued integration of AI-driven insights from its RADR® platform, will support more informed discussions with regulators and prospective collaborators regarding potential registration-oriented strategies for LP-300. Differentiated Safety Pro Currently Approved Post-TKI Combinations A central commercial rationale for the focused HARMONIC™ design is the differentiated safety pro LP-300 plus chemotherapy relative to currently approved post-TKI regimens. In the recently published Phase 3 MARIPOSA-2 trial, amivantamab plus chemotherapy — now FDA-approved for EGFR-mutant NSCLC following progression on osimertinib — was associated with substantial rates of treatment-related serious adverse events, infusion reactions, and dermatologic toxicities that complicate real-world administration. Preliminary HARMONIC™ data (Data Cutoff: April 13, 2026; n=31 receiving LP-300 + chemotherapy) suggest a materially more manageable safety pro LP-300 is added to a carboplatin/pemetrexed backbone: The table below summarizes observations regarding Treatment-Related Adverse Events (TRAE) and Treatment-Emergent Adverse Events (TEAE). A Treatment-Emergent Adverse Event in clinical trials is an unfavorable medical occurrence that starts or worsens in intensity or frequency after the first dose of study treatment. Adverse Event (any grade unless noted) LP-300 + Chemo (N=31) Amivantamab + Chemo (N=130)¹ Treatment-related serious adverse event 3% 23% TEAE leading to dose delay (any study drug) 19% 65% TEAE leading to drug discontinuation 6% 18% Infusion-related reaction (TRAE) 7% 58% Rash (TRAE) 7% 43% Paronychia (TRAE) 0% 36% Stomatitis (TRAE) 0% 31% ¹ Cross-trial comparison; not a head-to-head study. Amivantamab + chemotherapy data from Passaro A, et al. Annals of Oncology 2024;35(1):77-90 (MARIPOSA-2). LP-300 + chemotherapy data are preliminary, HARMONIC™ trial Data Cutoff: April 13, 2026. The cleaner tolerability pro particularly relevant in the post-TKI L858R setting, where patients have already been heavily pretreated and where treatment-emergent toxicities can drive dose interruptions, premature discontinuation, and erosion of efficacy in clinical practice. Lantern believes this safety differentiation, together with the emerging efficacy signal in the L858R subgroup, positions LP-300 as a potential future best-in-tolerability option in a treatment setting that currently demands meaningful infrastructure and supportive-care resources. Ongoing Trial Progress and Emerging Clinical Data The HARMONIC™ trial is currently enrolling patients at clinical sites in the United States and Taiwan, following the completion of targeted enrollment in Japan in July 2025 across five clinical centers, including the National Cancer Center Tokyo. Taiwan represents a particularly important region for HARMONIC™, as more than half of lung cancer cases there occur in never-smokers, underscoring the global relevance of LP-300 for this patient population. The trial has already generated encouraging early clinical data: in its initial safety lead-in cohort in the United States, LP-300 in combination with carboplatin and pemetrexed demonstrated an 86% clinical benefit rate and a 43% objective response rate among the first seven patients enrolled, including one patient who achieved a durable complete response in target lesions that has now been sustained for more than two years. Additional emerging data presented in April 2026 showed a median progression-free survival of 8.3 months in EGFR exon 21 L858R-mutant patients treated with the LP-300 triplet after TKI failure, with no new safety signals and no clinically meaningful toxicity added beyond that of carboplatin and pemetrexed alone. KOL Webinar: Never-Smoker Lung Cancer – May 21, 2026 Rodman & Renshaw is hosting a fireside chat with Joseph Treat, M.D., on Thursday, May 21, 2026, from 3:00 to 4:00 PM ET, moderated by Michael G. King, Jr., Senior Biotechnology Analyst at Rodman & Renshaw. Dr. Treat is Professor Emeritus in the Division of Medical Oncology at Fox Chase Cancer Center and has focused his clinical research exclusively on lung cancer since 1991, when he founded the first medical oncology thoracic program at the University of Pennsylvania Cancer Center. His prior work as a Senior Fellow at Eli Lilly on a Phase III anti-VEGF trial in EGFR-mutated lung cancer led to regulatory approvals by the FDA, EMA, and Japanese authorities, and his current research focuses on lung cancer in individuals who have never smoked. The discussion will address the evolving treatment landscape in lung cancer, the unmet need in never-smoker populations, and what durable disease control could mean for real-world patient outcomes. To register, please click here . Lantern is actively exploring collaboration and partnering opportunities, both globally and regionally, to maximize the commercial potential of LP-300 across multiple geographies where never-smoker NSCLC is an increasingly recognized clinical challenge. The Company expects to provide additional clinical data updates from the HARMONIC™ trial, including outcomes in the enriched EGFR exon 21 L858R cohort under the amended protocol, in the second half of 2026. About LP-300 and the HARMONIC™ Trial LP-300 is an investigational small molecule being evaluated in Lantern Pharma's Phase 2 HARMONIC™ trial in combination with carboplatin and pemetrexed in never-smokers with advanced NSCLC adenocarcinoma who have progressed following treatment with EGFR tyrosine kinase inhibitors. Following a successful Type C meeting request outcome, HARMONIC™ is transitioning to a single-arm design that will enrich enrollment for patients with EGFR exon 21 L858R mutations and extend LP-300 dosing to a maximum of eight cycles. The trial is enrolling patients at clinical sites in the United States and Taiwan, with completed targeted enrollment in Japan. The HARMONIC™ trial is registered on ClinicalTrials.gov under identifier NCT05456256. LP-300 has not received FDA marketing approval for any indication. About Lantern Pharma Lantern Pharma Inc. (NASDAQ: LTRN) is a clinical-stage, AI-driven precision oncology company developing targeted therapies for high-need cancer indications. The Company's proprietary RADR® AI platform integrates multi-omic biomarker data with clinical outcomes to identify patient subgroups most likely to respond to specific therapies, enabling more efficient clinical development and biomarker-driven trial design. Lantern's pipeline includes LP-300 (HARMONIC™ trial in never-smoker NSCLC), LP-184, and LP-284, with additional preclinical programs identified through RADR®. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements include, among other things, statements relating to: future events or our future financial performance; the planned implementation of protocol amendments and transitioning of the study design for the HARMONIC™ clinical trial; the planned development pathway for LP-300 in patients harboring the EGFR exon 21 L858R mutation; LP-300’s potential clinical activity and tolerability profile; our clinical development plans; expectations and estimates regarding clinical trial timing and patient enrollment; estimates regarding patient populations, potential markets and potential market sizes; and our plans to discover and develop drug candidates and to maximize their commercial potential by advancing such drug candidates ourselves or in collaboration with others. Any statements that are not statements of historical fact (including, without limitation, statements that use words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “target,” “model,” “objective,” “aim,” “upcoming,” “should,” “will,” “would,” or the negative of these words or other similar expressions) should be considered forward-looking statements. There are a number of important factors that could cause our actual results to differ materially from those indicated by the forward-looking statements, such as (i) the risk that we may not be able to secure sufficient future funding when needed and as required to advance and support our existing and planned clinical trials and operations, (ii) the risk that observations in preclinical studies and emerging or preliminary observations in clinical studies do not ensure that later observations, studies and development will be consistent or successful, (iii) the risk that the planned development of LP-300 for treatment of patients harboring the EGFR exon 21 L858R mutation may not be successful, (iv) the risk that any clinical benefit observed to date relating to LP-300 may not be reproduced in the completed HARMONIC™ trial or in larger or confirmatory studies, (v) the risk that clinical data referenced in this press release are exploratory and preliminary, based on small patient cohorts, and may not be representative of outcomes in broader populations, (vi) the risk that cross-trial comparisons are provided for context only and should not be interpreted as direct evidence of comparative safety or efficacy, (vii) the risk that our research and the research of our collaborators may not be successful, (viii) the risk that we may not be successful in licensing our product candidates or in completing potential partnerships and collaborations, (ix) the risk that none of our product candidates has received FDA marketing approval, and we may not be able to successfully initiate, conduct, or conclude clinical testing for or obtain marketing approval for our product candidates, and (x) those other factors set forth in the Risk Factors section in our Annual Report on Form 10-K for the year ended December 31, 2025, filed with the Securities and Exchange Commission on March 30, 2026. You may access our Annual Report on Form 10-K for the year ended December 31, 2025, under the investor SEC filings tab of our website at or on the SEC’s website at . Given these risks and uncertainties, we can give no assurances that our forward-looking statements will prove to be accurate, or that any other results or events projected or contemplated by our forward-looking statements will in fact occur, and we caution investors not to place undue reliance on these statements. All forward-looking statements in this press release represent our judgment as of the date hereof, and, except as otherwise required by law, we disclaim any obligation to update any forward-looking statements to conform the statement to actual results or changes in our expectations. Contacts Investor & Media Contact Investor Relations | ir@lanternpharma.com | +1-972-277-1136