Enfuvirtide

Jeremy B. Fitch, MBA, appointed as Chief Business Officer Michael A. Alrutz, J.D., Ph.D., appointed as General Counsel Guy C. Ruble, PharmD, appointed as VP, Regulatory Affairs CAMBRIDGE, United Kingdom and NEW YORK, May 04, 2026 – Artios Pharma Limited (“Artios” or “the Company”), a clinical-stage biopharmaceutical company pioneering the development of new classes of DNA Damage Response (DDR) medicines to deliver meaningful survival benefits for patients with cancer, today announced the appointment of three senior executives to the leadership team as the Company accelerates its potential first-in-class oncology pipeline. Jeremy B. Fitch, MBA, joins as Chief Business Officer (CBO) and will shape Artios’ corporate business development and strategic partnerships. Michael A. Alrutz, J.D., Ph.D., joins as General Counsel and will oversee Artios’ legal, corporate governance, regulatory compliance, risk management, and intellectual property management, while serving as a strategic partner to the Board of Directors and executive leadership team. Guy C. Ruble, PharmD, has been appointed as Vice President of Regulatory Affairs to lead the Company’s regulatory strategy and initiatives. These appointments come as Artios advances alnodesertib into late-stage development and prepares for potential U.S. commercialization, executes a randomized Phase 2 study for ART6043, and rapidly advances its DNA Damage Response antibody drug conjugate platform toward clinical development. “Jeremy brings a proven track record of executing high‑impact transactions and shaping portfolio and corporate strategy,” said Mike Andriole, Chief Executive Officer of Artios. “His appointment as CBO, together with Michael’s deep legal and governance expertise and Guy’s leadership in global regulatory strategy, comes at a pivotal inflection point as we progress alnodesertib toward potential registration and commercialization. These leadership additions further strengthen our ability to execute with discipline, accelerate paths to registration, and urgently deliver first‑in‑class therapies to patients with late‑stage cancers who need more treatment options.” “With three potentially first-in-class DDR programs under rapid development, Artios is uniquely positioned with a differentiated pipeline and clear opportunities to create long-term value,” said Jeremy B. Fitch, MBA, Chief Business Officer of Artios. “I look forward to working with the rest of the management team to develop and execute value-creating transactions which leverage our substantial DDR scientific and clinical expertise.” Jeremy B. Fitch, MBA, Chief Business Officer Jeremy joins Artios with more than 30 years of experience in the biopharmaceutical industry with Eli Lilly and Company (“Lilly”), across operational, financial, and corporate business development roles. Jeremy spent the past 15 years in Lilly’s Corporate Business Development group, most recently as Vice President of Transactions, where he led strategic deal-making spanning M&A, asset acquisitions/divestitures, and licensing agreements. Having led more than $5 billion in transactions during his career, Jeremy has been central to developing and implementing strategies that have driven substantial value creation across Lilly’s pipeline. Jeremy is a Certified Licensing Professional and holds an MBA from Duke University’s Fuqua School of Business. Michael A. Alrutz, J.D., Ph.D., General Counsel Dr. Alrutz is a seasoned General Counsel and Corporate Secretary, bringing 25 years of biotechnology legal affairs experience to Artios across both private and public biopharmaceutical companies. Dr. Alrutz brings a strong track record advising leadership teams through complex corporate inflection points, including IPOs, follow-on financings, intellectual property matters, pre-commercialization matters, and high-value corporate transactions. Most recently, he was SVP, General Counsel, Secretary, and Chief Compliance Officer at Chimerix, where he led SEC compliance, board governance, intellectual property management, and the legal facets of corporate transactions, including the company’s $935 million all-cash merger with Jazz Pharmaceuticals as the company prepared for commercialization of Modeyso® (dordaviprone). Previously, while General Counsel at Trimeris, Inc., he provided legal counsel for the company’s commercial launch of its antiretroviral, Fuzeon® (enfuvirtide). Dr. Alrutz is registered to practice before the USPTO, and holds a J.D. from Duke University School of Law, and a Ph.D. in Microbiology and Molecular Biology from Tufts University. Guy C. Ruble, PharmD, VP of Regulatory Affairs Guy brings more than 20 years of regulatory affairs leadership and nearly three decades of biopharmaceutical industry experience to Artios. He most recently served as Vice President of Regulatory Affairs at Iovance Biotherapeutics, where he led the U.S. FDA accelerated approval of AMTAGVI® (li ), the first tumor-infiltrating lymphocyte (TIL) therapy approved in the United States and Canada, and also led global submissions across Europe and Asia. Prior to Iovance, Guy spent nearly 23 years at Eli Lilly and Company, leading global regulatory strategy for multiple oncology programs, including the U.S. FDA approval of Verzenio® (abemaciclib). He earned recognition as a Top 100 Lilly Innovator. Guy holds a Doctor of Pharmacy (PharmD) from Purdue University and is Regulatory Affairs Certified (RAC-US). He is a member of the Regulatory Affairs Professional Society and the American Society of Clinical Oncology. About Artios Pharma Ltd. Artios’ mission is to develop new classes of medicines that harness DNA Damage Response (DDR) pathways, targeting DNA replication stress and synthetic lethality, to deliver meaningful survival benefits for patients with cancer. Its three potentially first-in-class programs, each with a novel mechanism of action, include ATR inhibitor alnodesertib, the DNA polymerase theta (Polθ) inhibitor ART6043, and a preclinical portfolio of DDRi-ADC candidates with novel payloads. Together, these programs are designed to eliminate cancer cells’ survival mechanisms, driving cancer cell death and improving clinical outcomes. Visit our website at to learn more about Artios. For more information, please contact: Trophic Communications Jacob Verghese or Verena Schossmann Tel: +49 151 7441 6179 Email: artios@trophic.eu Attachment Artios Leadership PR

今天给大家分享一种量化抗体可变区人源化程度的计算框架（T20评分），旨在解决已有计算工具无法准确区分人源与非人源抗体序列的痛点问题，对于临床前抗体药物开发具有极大的应用价值 。一、 研究背景🔍 单克隆抗体疗法在肿瘤、自身免疫及神经系统疾病等治疗中发挥着不可替代的作用 。然而，早期抗体（如纯鼠源抗体）由于含有大量非人源序列，在人体内极易诱发抗药抗体（ADAs）的产生 。ADAs 不仅会中和药物活性导致药物疗效锐减，还可能引发从注射部位皮疹到致命性全身炎症的严重不良反应 。因此，在将药物推进至临床试验之前，能够准确预测并评估候选抗体的免疫原性风险，是抗体药物研发中亟待解决的核心痛点 。由于抗体中包含的人源序列越多，其免疫原性通常越低，因此提高抗体序列的“人源化程度”成为了降低免疫原性的标准策略 。 为了量化评估抗体的人源化程度，过往研究提出了多种计算工具（如 H-score 和 G-score） 。然而，这些早期算法依赖的参考数据库体量极小（仅约3500条序列），存在明显的底层局限性 。最致命的缺陷在于，它们无法在评分上清晰地将人类抗体序列与小鼠抗体序列隔离开来，导致大量鼠源重链和轻链的得分与人源序列高度重叠 。如果一种评分系统在算法源头就无法精准分辨不同物种特征差异，就无法真正有效地指导抗体的人源化设计与后续免疫原性预测 。二、研究方法🧩 为了突破现有工具的局限，研究团队开发了全新的 T20评分分析器 (T20 score analyzer) 。研究人员首先通过高通量数据抓取，构建了一个庞大的抗体序列数据库，其中包含约 38,700 条纯人类抗体可变区序列，并利用 Kabat 编号系统对所有序列进行标注，精准拆分出互补决定区 (CDRs) 和骨架区 (framework) 。该数据库被精细划分为完整的重链 (VH)、Kappa轻链 (VK) 和 Lambda轻链 (VL) 序列库，以及对应的去除 CDR 后的纯骨架区序列库 。 在评分算法层面，系统将输入的抗体序列与对应数据库进行 protein BLAST 序列比对，提取匹配度最高的前20条序列的序列等同性 (percent identity) 的平均值作为该候选抗体的 T20 评分 。为了进一步消除人源库中极端异常序列对评分区分度的干扰，研究人员创新性地在分布尾部切了一刀，移除了数据库中评分最低的 15% 序列，构建了纯净度极高的“T20 阈值人类数据库 (T20 Cutoff Human Databases)” 。 这一关键的数据清洗步骤确立了明确的“人源化阈值”，使得评分算法在区分人源与非人源序列时展现出了极高的特异性 。 Fig 1：T20 评分分析器开发与数据库清洗流程图 描述：(A) 抗体序列处理与 Kabat 编号标注。(B) 利用 BLAST 匹配 Top 20 序列并计算平均序列等同性得出 T20 评分。(C) 剔除底部 15% 序列确立 T20 人源化阈值。 三、 结果与讨论📊 在使用剔除了底部干扰序列的 T20 阈值数据库后，T20 评分展现出了极其干脆的物种分辨能力 。绝大部分真实人类抗体序列的得分稳稳地落在阈值之上，而几乎所有的小鼠全长及骨架序列得分均大幅度跳水至阈值以下，人鼠两组序列在评分分布上的重叠区间被压缩到了极点 。 Fig 2：使用 T20 阈值数据库大幅提升人源与鼠源序列的区分度 描述：左图为使用全量人类数据库的评分分布（有重叠），右图为使用剔除底部 15% 序列的阈值数据库后的分布情况（重叠显著减少）。 这一高特异性评估能力在独立验证集、人类生殖系序列 (germline) 以及涵盖从硬骨鱼类到非人灵长类的 12 种不同物种的广泛抗体库测试中得到了全面验证 。数据严谨地显示，除猕猴等高度同源的非人灵长类动物和转基因小鼠产生的人源抗体外，其余所有非灵长类动物的序列均被精准拦截在人源化阈值之下 。 Fig 3：涵盖多种物种库的 T20 评分系统特异性验证 描述：分别在全长序列 (A-C) 和纯骨架序列 (D-F) 上测试多种动物来源抗体，非灵长类序列均无法通过人源化阈值验证。 在针对 98 种实际处于临床阶段的治疗性单抗（涵盖纯鼠源、嵌合、人源化及全人源抗体）的横向测评中，T20 评分异常敏锐地捕捉到了抗体在经历人源化改造后序列得分的显著跃升 。对比测试表明，传统的 H-score 和 G-score 虽然在趋势上与 T20 相关，但在统计显著性上远不及 T20，T20 评分能够以更小的 P-value 显著区分鼠源/嵌合抗体群与人源化/全人源抗体群 。 Fig 4：T20 评分与传统 H-score及 G-score 对临床治疗性抗体的区分能力对比 描述：T20 评分 (B-E图上方) 相较于 H-score (中间) 和 G-score (下方) 能更精准、显著地拉开不同人源化程度抗体群体之间的评分差距。 最引人瞩目的是，当研究者将这 65 种单抗的 T20 评分直接拟合其真实的临床免疫原性数据（ADA发生率）时，发现了一条干脆的负相关曲线：T20 评分越高，抗体诱发 ADA 的发生率越低 。令人惊喜的是，尽管全人源抗体在全长序列的得分略高于人源化抗体，但在临床呈现的实际免疫原性水平上两者基本持平 。只要人源化抗体的纯骨架区 (framework only) T20 得分能够跨越人源化阈值，其安全性表现就完全可以媲美全人源抗体 。 Fig 5：治疗性抗体 T20 评分与临床免疫原性的负相关性分析 描述：数据显示 T20 得分升高伴随免疫原性显著下降。图中可见人源化抗体（绿点）与全人源抗体（红点）在免疫原性极低区间表现出高度一致性。 通过持续追踪 3 款从高免疫原性鼠源分子成功升级为人源化版本的临床抗体，可以直观地看到：随着重轻链骨架区的 T20 评分稳步跨过设定的安全性阈值，其临床免疫原性发生率呈断崖式下跌，彻底归零 。这不仅证实了人源化工程的绝对必要性，也完美佐证了 T20 评分在实战中的强大预测能力 。 Fig 6：三款临床抗体在人源化改造前后的免疫原性与 T20 评分动态追踪 描述：随着鼠源抗体（蓝点）被改造为人源化版本（空心点），T20 得分增加的同时，免疫原性均降低至 0%。 四、 总结📌 总体而言，T20 评分系统为单抗的人源化序列筛选提供了一种高特异性、高分辨度且极具实操性的量化标尺 。该文献以扎实的大样本数据粉碎了业界对“全人源抗体绝对优越性”的刻板印象，证明了：在研发实战中，只要通过理性的蛋白质工程改造，使抗体骨架区的 T20 评分触达甚至超越人类序列安全阈值，人源化抗体即可完全消除免疫原性隐患，达到与纯全人源抗体并驾齐驱的临床安全性 。这对于当今 AI 驱动抗体设计（AIDD）和早期抗体药物发现管线而言，不仅是一种高效的底层质控算法，更能够大幅优化研发路径、节约全人源发现平台的巨额成本 。 参考资料  Gao, S.H., Huang, K., Tu, H. et al. Monoclonal antibody humanness score and its applications. BMC Biotechnol 13, 55 (2013).  以上只代表个人的观点，文中信息不当或不准确的地方，欢迎留言或私信指正。  ------关注我，学习更多AIDD文献🔍------