Phase II Randomized Study Evaluating a Pragmatic Approach to Adoptive Cell Therapy (ACT) Using an IL2 Analog (ANV419) vs High Dose IL2 After Tumor Infiltrating Lymphocytes (TIL) Therapy in Patients With Melanoma, NSCLC and Cervical Cancer

Background:
The presence of T-lymphocytes in resected tumor samples derived from long-term survival patients and the fact that reinvigoration of their functionality through the administration of specific immune-therapies can lead to remarkable antitumor responses supports that lymphocytes play a critical role in cancer immunity.
TIL-based ACT (Adoptive cell therapy using tumor-infiltrating lymphocytes product) is a modality of ACT used to treat patients with multiple types of cancer and it consists in the adoptive transfer of ex vivo expanded autologous tumor-infiltrating lymphocytes obtained from tumor resection or tumor biopsies in patients following a non-myeloablative lymphodepleting (NMA-LD) chemotherapy. Ex vivo expansion of TIL relies on the non-specific expansion of lymphocytes present in tumor single cell suspensions or tumor fragments in high dose IL-2.
Although proven efficacy in selected, the HD-IL-2 use remains relatively restricted due to toxicity. Due to the short serum half-life and the need to achieve an immune-modulatory effect in the tissues, IL-2 must be given in doses that induce severe systemic toxicities, including capillary leak syndrome (CLS), pulmonary edema, hypotension, acute renal insufficiency, and rarely myocarditis, limiting its applicability in cancer. Studies comparing HD-IL-2 with lower doses both in renal cell carcinoma and metastatic melanoma to minimize toxicity demonstrated the superiority of the high dose regimens in both diseases. These drawbacks of HD-IL-2 use encouraged the development of improved IL-2-based biologic agents with higher selectivity for effector immune cell subsets, reduced toxicity, and prolonged half-life.
ANV419 is a novel IL-2 agent, which has been developed as a preferentially IL-2Rβγ directed fusion protein with a longer half-life. It has shown high effector selectivity and a favorable safety profile in preclinical testing, including in nonhuman primates, and it has been investigated in an ongoing open-label, dose-escalation Phase I Study in multiple tumor types. he safety profile of ANV419 is characterized by pyrexia, nausea, vomiting, ALT/AST changes and CRS in some patients. Most events are low grade and self-limiting and manageable with standard supportive care. ANV419 was well-tolerated by most patients. No patient discontinued treatment due to treatment related AE.
Taking all the previous information into account, the primary objectives of this study are:
1. To determine whether TIL-ACT using the IL-2 analog ANV419 reduces the mean number of predefined grade ≥3 relevant adverse events related to interleukin use (based on Common Terminology Criteria for Adverse Events v5.0 - CTCAE v5.0) compared to TIL-ACT using HD-IL-2.
2. To determine whether TIL-ACT using the IL-2 analog improves patient´s reported outcomes (PRO) compared to TIL-ACT using HD-IL-2

开始日期2025-01-15

申办/合作机构

Vall d'Hebron Institut d'Oncologia

[+1]

NCT05641324

/ Terminated临床1期

A Phase 1 Study of ANV419 as Monotherapy, and ANV419 in Combination With Daratumumab or With Lenalidomide Plus Low-Dose Dexamethasone, in Patients With Relapsed or Refractory Multiple Myeloma (OMNIA-2)

The purpose of this study is to evaluate the safety and tolerability of ANV419 monotherapy followed by ANV419 in combination with lenalidomide plus low-dose dexamethasone or ANV419 in combination with daratumumab.

开始日期2023-02-10

申办/合作机构

Anaveon AG

NCT05578872

/ Completed临床1/2期

A Phase 1/2 Study of ANV419 as Monotherapy or in Combination With Anti-PD-1 or Anti-CTLA-4 Antibody Following Anti-PD-1/Anti-PD-L1 Antibody Treatment in Patients With Unresectable or Metastatic Cutaneous Melanoma (OMNIA-1)

The purpose of this study is to evaluate the efficacy and safety of ANV419 monotherapy or the combination of ANV419 with anti-PD1 antibody or with anti-CTLA4 antibody in adult participants with advanced (unresectable or metastatic) cutaneous melanoma. The study has 3 parts. Part 1 to evaluate ANV419 in monotherapy and Parts 2 and 3 to evaluate ANV419 in combination with anti-PD1 antibody or anti-CTLA4 antibody. Parts 2 and 3 were not initiated, as the prespecified efficacy criteria to graduate to Part 2 were not met at the interim analysis of Part 1.

开始日期2022-12-16

申办/合作机构

Anaveon AG

100 项与 ANV-419 相关的临床结果

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100 项与 ANV-419 相关的转化医学

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100 项与 ANV-419 相关的专利（医药）

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项与 ANV-419 相关的文献（医药）

2024-12-31·mAbs

Discovery and development of ANV419, an IL-2/anti-IL-2 antibody fusion protein with potent CD8+ T and natural killer cell-stimulating capacity for cancer immunotherapy

Article

作者: Regnier, Catherine ; Rondeau, Jean-Michel ; Popp, Simone ; Katopodis, Andreas ; Egli, Nicole ; Huber, Christoph ; Richter, Kirsten ; Murer, Patrizia ; Petersen, Laetitia ; Brannetti, Barbara

Novel engineered IL-2 agonists strive to increase the therapeutic window of aldesleukin (human IL-2) by increasing selectivity toward effector over regulatory T cells and reducing dose-limiting toxicities. Here we describe ANV419, an IL-2/anti-IL2 antibody fusion protein designed for selective IL-2 receptor βγ (IL-2 Rβγ) activation by sterically hindering IL-2 from binding to IL-2 Rα. The fusion protein has an IL-2 connected to the light chain complementarity-determining region (CDR) domain of a humanized antibody that binds to IL-2 at the same epitope as IL-2 Rα. Optimization of the selectivity and pharmacological properties led to the selection of ANV419. ANV419 preferentially expands CD8⁺ T cells and natural killer (NK) cells over T_regs and can be safely administered at doses that elicit strong pharmacodynamic effects and efficacy in mouse tumor models. Its anti-tumor efficacy was enhanced when combined with programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors. ANV419 also enhances the NK cell killing capacity and increases tumor growth inhibition when used alongside trastuzumab in a Her-2⁺ xenograft mouse model. In cynomolgus monkeys, the estimated half-life of ANV419 is 24 h, and doses that induced sustained expansion of effector cells were well tolerated without the severe toxicities typically observed with high-dose IL-2. These data support the clinical development of ANV419 in solid tumors and hematological malignancies as monotherapy and in combination with checkpoint inhibitors or agents that induce antibody-dependent cellular cytotoxicity. ANV419 is currently in Phase 1/2 clinical development and may provide cancer patients with a wider therapeutic window than aldesleukin.

2024-05-01·Journal for ImmunoTherapy of Cancer

Phase 1 first-in-human dose-escalation study of ANV419 in patients with relapsed/refractory advanced solid tumors

Article

作者: Stephane Champiat ; Aurelien Marabelle ; Yohann Loriot ; Justin Cagnat ; Julia Delahousse ; Laurent Mathiot ; Francois-Xavier Danlos ; David Combarel ; Santiago Ponce ; Sophie Broutin ; Kaissa Ouali

Patients with advanced cancer, previously treated with immune checkpoint blockade therapy, may retain residual treatment when undergoing the initial infusion of experimental monotherapy in phase 1 clinical trials. ANV419, an antibody-cytokine fusion protein, combines interleukin-2 (IL-2) with an anti-IL-2 monoclonal antibody, aiming to stimulate the expansion of CD8 T and natural killer lymphocytes while restricting regulatory T lymphocytes. In the recent publication of the phase 1 dose escalation study of ANV419, a notable gap exists in detailed information regarding patients’ prior antitumoral treatments, specifically programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) targeted monoclonal antibodies. Some patients likely retained residual anti-PD-1/PD-L1 monoclonal antibodies, potentially influencing the outcomes of ANV419. In a separate clinical cohort, we retrospectively measured the residual concentration of nivolumab and pembrolizumab, revealing persistent serum concentrations of anti-PD-1/PD-L1 antibodies even months after treatment cessation. This underscores the importance of comprehensively documenting prior immunotherapy details in clinical trials. Such information is crucial for understanding potential interactions that may impact both immunological and clinical effects.

2023-11-01·Journal for immunotherapy of cancer

Phase 1 first-in-human dose-escalation study of ANV419 in patients with relapsed/refractory advanced solid tumors

Article

作者: Sanchez Perez, Vicky ; Bucher, Christoph ; Corral de la Fuente, Elena ; Joerger, Markus ; Calvo, Emiliano ; Jethwa, Sangeeta ; Alonso, Guzmán ; Lopez, Juanita ; Garralda, Elena ; Hess, Dagmar ; König, David ; Laubli, Heinz

Background:

ANV419 is a stable antibody–cytokine fusion protein consisting of interleukin-2 (IL-2) fused to an anti-IL-2 monoclonal antibody that sterically hinders binding of IL-2 to the α subunit of its receptor but has selective affinity for the receptor βγ subunits. Thus, ANV419 preferentially stimulates CD8+ effector T cells and natural killer cells which are associated with tumor killing, while minimizing the activation of immunosuppressive regulatory T cells.

Methods:

ANV419-001 is an open-label, multicenter, phase 1 study to evaluate the safety, tolerability, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ANV419. Secondary objectives were to characterize the pharmacokinetics, pharmacodynamics and tumor response. Adult patients with advanced solid tumors and disease progression after ≥1 previous line of systemic therapy were enrolled. ANV419 was administered by intravenous infusion once every 2 weeks, with a planned treatment duration of 12 months. The dose escalation part of the study explored doses 3, 6 and 12 µg/kg as single patient cohorts followed by 24–364 µg/kg in a 3+3 design. Interim results are reported here (data cut-off: March 22, 2023).

Results:

Forty patients were enrolled and received at least one dose of ANV419. The MTD and RP2D were determined to be 243 µg/kg. The most common ANV419-related treatment-emergent adverse events were Grade 1 and 2 fever (31 (77.5%)), chills (23 (57.5%), vomiting (14 (35.0%)), cytokine release syndrome and nausea (12 (30.0%) each). Transient and self-limiting lymphopenia due to lymphocyte redistribution was observed in all patients. In the RP2D cohort, Grade ≥3 thrombocytopenia and fever were reported by one patient (12.5%) each. All events were manageable with standard supportive care. At doses of 243 µg/kg (RP2D/MTD), the estimated T1/2 was approximately 12 hours. At ANV419 doses ≥108 µg/kg, 64% of patients had a best response of at least SD (15 SD and 1 confirmed PR).

Conclusions:

ANV419 at doses up to 243 µg/kg (the RP2D) was well tolerated and showed signs of antitumor activity in a heavily pretreated patient population with advanced solid tumors.

Trial registration number:

NCT04855929.

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·博药

All-in冷门靶点：Forte Bio的18天逆风之路

创新药作为典型的高风险、长周期赛道，具备极高的商业价值天花板，往往一款成功的产品就足以重塑一家企业的命运，也承载着难以替代的社会价值与科研成就感。但同时，行业普遍存在的路径依赖，也让绝大多数参与者局限于成熟靶点与适应症的内卷之中，这正是GLP-1、PCSK9这类具备全新设计思路的颠覆性产品始终稀缺的核心原因。 2026年7月，处于临床阶段的美国生物科技公司Forte Biosciences以单月超260% 的涨幅登顶美股生物科技板块涨幅榜榜首，成为全球资本市场最受关注的核心标的。而这场暴涨的核心驱动力，正是其管线背后差异化的全新药物设计逻辑： 2026年7月9日，Forte公布FB102治疗白癜风的Ib期临床阳性结果，受试者病情改善显著；叠加此前乳糜泻适应症的Ib期积极信号，市场迅速认可了该分子的跨适应症潜力，资金大幅涌入。 2026年7月27日，自免领域巨头Argenx宣布以22亿美元全额收购Forte，溢价超40%，将早期临床的概念验证价值彻底落地为实打实的商业对价，也进一步夯实了Argenx在全球自免赛道的龙头地位。短短18天，Forte Biosciences从一家二线临床阶段Biotech跃升至22亿美元的并购标的，让市场再次见证了早期创新资产的估值爆发力。但很少有人记得，就在五年前，这家公司曾走到退市清算的悬崖边缘。借壳上市的明星管线，一夜折戟 Forte Biosciences的资本起点，是2020年的借壳上市。彼时公司通过反向收购已上市的脑癌基因疗法企业Tocagen登陆纳斯达克，业务聚焦皮肤疾病领域，核心资产为外用活菌生物疗法FB-401，活性成分为黏膜玫瑰单胞菌，主打通过调节皮肤菌群治疗特应性皮炎。凭借早期研究中良好的安全性与初步疗效信号，FB-401在公司上市后数月便获得FDA快速通道资格，被资本市场视为特应性皮炎赛道的潜力挑战者，一时风头无两。但命运的转折来得猝不及防。 2021年9月，FB-401治疗特应性皮炎的II期临床顶线结果公布：主要终点未达标：EASI-50（湿疹面积及严重程度指数改善50%）指标上，FB-401组为58.0%，安慰剂组为60.0%，p=0.7567，试验药疗效未优于安慰剂。次要终点无统计学差异：EASI-90指标上，FB-401组为27.6%，安慰剂组为20.5%，p=0.3075，仅呈现微弱数值趋势。作为当时公司唯一一款处于临床阶段的管线，FB-401的失败相当于直接宣判了原有业务的终结。消息公布后两个交易日，公司股价暴跌85%，市值几乎归零，距离破产清算仅一步之遥。截至2021年底，Forte账面现金仅剩4200万美元，团队大幅收缩，管理层开始公开评估出售、合并、资产授权等全部战略选项。在行业普遍看来，这家上市仅一年多的 Biotech，已经进入了生命倒计时。豪赌：All-in冷门靶点，走差异化机制路线就在所有人都认为Forte将草草收场之时，拥有深厚华尔街背景、深谙资本市场估值逻辑的CEO Paul Wagner博士做出了出乎行业意料的决策：“彻底砍掉皮肤菌群疗法等全部旧有业务，将仅剩的资金、团队等所有资源，全部押注于当时仍处于临床前阶段的抗体分子FB102”。图片来源：Forte Bio官网不得不说，这一决定可谓一场豪赌。毕竟FB102作为一款靶向CD122（IL-2/IL-15受体β亚基）的单克隆抗体，在当时已是十分冷门的开发方向，更何况FB102的药物开发路径还并非激动剂策略，而是拮抗剂策略。数据来源：公开数据整理 CD122靶点的药物开发历来可分为两条技术路径，即：激动剂策略：主要用于肿瘤免疫治疗，通过偏向性激活CD122/IL-2Rβγ通路增强效应T细胞的杀伤能力，是当时的热门赛道，代表产品包括Anaveon的ANV419、Medicenna的MDNA11、信达生物的IBI363以及Nektar的NKTR-214等。拮抗剂策略：主要用于自身免疫病，通过阻断IL-2/IL-15信号抑制病理性组织驻留记忆T细胞（TRM），代表产品为Forte的FB102与AnaptysBio的ANB033。而CD122拮抗剂之所以冷门，主要源于传统认知中，CD122拮抗剂会非特异性阻断IL-2与IL-15的全部信号，在抑制致病性T细胞的同时，也会削弱维持免疫耐受的调节性T细胞（Treg）功能，理论上存在破坏免疫稳态、提升感染风险的隐患。因此当时行业的主流选择，要么是开发CD122激动剂用于肿瘤领域，要么是靶向更上游的IL-15——既能精准调控TRM通路，又能最大程度保留IL-2对Treg的支持作用，安全性逻辑更自洽。但也正是如此，Forte团队在其中也看到了差异化的本质机会：Treg细胞表面表达的是高亲和力三聚体IL-2受体（CD25/CD122/CD132），而致病性CD8+T细胞、NK细胞主要表达中低亲和力的二聚体受体（CD122/CD132）。如果能通过抗体工程优化，实现对CD122的选择性阻断——优先抑制二聚体受体介导的致病性免疫细胞激活，同时最大程度保留三聚体受体对Treg的支持功能，或许就能在保证安全性的前提下，实现比单纯抗IL-15更深、更持久的疾病缓解。并且，这条路径还有机会清除组织中潜伏的免疫记忆细胞，直击自身免疫病“停药即复发”的核心临床痛点，具备实现功能性治愈的潜力。因此，Paul Wagner带领的管理层在承受来自股东的大量质疑与清算压力的情况下，毅然踏上了这场没有退路的豪赌，最终还是以破釜沉舟的定力，将有限的资源全部集中到FB102的临床推进上。逆袭：两份阳性报告，完成价值跃迁事实证明，Forte确实赌对了，从两份扎实的概念验证数据开始，Forte的翻身仗正是打响。 2025年，FB102公布乳糜泻Ib期积极数据：在仅32名受试者的试验中，接受麸质激发后，FB102组的组织学复合终点显著优于安慰剂组，p值达到0.0099。这是FB102首次在人体中验证了机制可行性。乳糜泻长期以来是自免药物开发的高失败率洼地，多款靶向药物先后折戟，患者尚无获批的药物治疗方案，仅能通过严格无麸质饮食控制病情。FB102的阳性信号，第一次让市场收起对这款冷门分子的轻视，开始认真审视其机制价值。 2026年7月9日，FB102公布的白癜风Ib期数据：治疗第24周，FB102组患者面部白癜风面积评分指数（F-VASI）较基线平均改善29.6%，安慰剂组仅为7.9%；在基线病情更严重的患者群体中，改善幅度更是达到43.2%，而安慰剂组仅0.5%。图片来源：Forte Bio官网更具颠覆性的是疗效的持续性：受试者仅接受了12周的治疗，停药后疗效不仅没有回落，反而持续加深——整体人群在12至24周期间，F-VASI评分额外改善8%，重症患者更是提升了14%；84%的FB102治疗患者实现持续改善，全程无一人病情恶化。这份数据精准击中了白癜风治疗的核心痛点：现有外用JAK抑制剂虽能暂时控制炎症、促进复色，但皮肤中潜伏的TRM细胞会长期留存，一旦停药极易复发。而FB102通过调控免疫记忆通路，实现了停药后的持续获益，完美印证了“长效化缓解” 的机制假说，也为整个自免领域提供了全新的药物设计思路。数据公布当日，Forte股价一度飙升约55%。曾经不被行业看好的冷门管线，一夜之间成为自免赛道最炙手可热的明星资产。而也正是此时，本就是Forte战略投资者的Argenx没有选择等待更后期的数据，毅然选择出手，在白癜风数据公布仅18天后，从财务股东直接升级为全资买家，抢在乳糜泻II期数据读出前锁定了这笔资产，避免后续数据读出后资产估值进一步抬升。复盘：22亿美元并购的四大底层逻辑一笔22亿美元的交易，买下的不只是一个处于Ib期的抗体分子，更是Forte在绝境中跑通的一套Biotech生存与增长逻辑。它的逆袭绝非偶然，而是四项核心能力共同作用的结果。 ① 极致差异化的机制设计：打造“管线级单品”核心壁垒 FB102的核心竞争力，从来不是“同时阻断两条通路”的概念，而是精准的选择性阻断能力。通过对抗体结合特性的优化，它实现了“精准修剪致病细胞、不破坏整体免疫平衡”的效果——既保证了疗效的深度与持久性，也预留了更优的安全窗口。更重要的是，这种靶向免疫记忆的机制具备广谱性：从白癜风到乳糜泻，再到斑秃、克罗恩病等更多T细胞驱动的自免疾病，一款分子即可覆盖多个适应症，真正实现 “一款产品即一条管线”的价值，这也是Argenx愿意支付高溢价的核心原因。 ② 精准的赛道卡位：避开红海，锚定真实临床需求 Forte没有跟风布局类风湿关节炎、银屑病这类玩家云集的热门自免适应症，而是锚定了白癜风、乳糜泻这类长期“缺医少药”的细分领域。白癜风虽不危及生命，但全球患者群体庞大、治疗周期极长、复发率高，现有外用制剂受使用面积限制，系统性疗法存在巨大临床空白；乳糜泻更是药物开发的“坟场”，历史失败率极高，患者几乎只能依靠严格饮食控制，临床需求极其迫切。这些赛道看似绝对体量不及大适应症，但竞争格局清晰，未满足需求明确，监管层面也有孤儿药、快速通道等政策支持，一旦做出有效临床数据，价值兑现的速度和弹性都远高于红海赛道。 ③ 绝境下的战略定力：管理层的复合视角与决断力从核心管线失败到All-in新靶点，Forte的每一步都走在悬崖边缘。Paul Wagner带领的团队，展现了极强的战略判断力与执行力：在公司最艰难的时刻，没有选择保守续命、分散投资的“安全策略”，而是敢于破釜沉舟，集中所有资源押注高潜力的差异化方向；面对股东的质疑与清算压力，依然坚持对靶点价值的判断，没有被短期市场情绪左右。尤其值得注意的是，管理层的华尔街背景让其具备独特的买方视角——深谙资本市场对创新资产的定价逻辑，清楚“什么样的差异化能兑现为商业价值”，而非单纯从科研视角做决策。这种产业 + 资本的复合视角，是很多Biotech团队稀缺的特质，也是 Forte能完成逆袭的关键前提。 ④ 高效的临床推进：用速度兑现价值从确定押注FB102，到连续在两个适应症拿到Ib期阳性概念验证，Forte用极快的临床推进速度，把科学潜力变成了实实在在的商业价值。对于现金流紧张的小型Biotech而言，时间就是最大的成本。越快拿出扎实的临床概念验证数据，就越快能获得资本市场认可，掌握融资与商务合作的主动权。Forte正是用高效的执行力，在最短时间内完成了资产价值的跃迁，也为自己争取到了被并购的最佳窗口。结语从濒临清盘到被免疫学巨头以22亿美元收购，Forte的故事充满了戏剧张力，但剥开戏剧化的外壳，其内核无比朴素：在创新药行业，所有的逆袭，本质都是科学的胜利与数据的兑现。它给所有身处周期低谷的Biotech留下了重要启示：热门赛道的拥挤故事终会退潮，真正能穿越周期的，永远是对临床需求的精准洞察、对差异化机制的深耕，以及拿出过硬临床数据的执行力。而Argenx的这笔天价收购，也为全球自免领域定下了新的价值标尺：那些瞄准免疫记忆、指向长效缓解甚至功能性治愈的差异化靶点，哪怕仍处于临床早期，只要完成了扎实的人体概念验证，就具备极高的商业价值。参考来源 1.Forte Bio官网 2.Forte FB102 Phase 1b Vitiligo Data 3.Forte Biosciences Corporate Presentation - December 2025 4.FB102 prevents histological damage and mitigates gluten challenge-induced symptoms in a celiac disease Phase 1b study 5.CD122（IL-2Rβ/IL-15Rβ）靶向药物开发进展总结 6.ASCO 2018 摘要靶点深度解读专题——CD122 END 博腾股份成立于2005年，为全球药企、生物科技公司及科研机构等提供从临床前研究到药品上市全生命周期的端到端CDMO服务，涵盖小分子药物、多肽与寡核苷酸药物、蛋白与偶联药物以及细胞与基因治疗药物的原料药到制剂全流程。截至2025年末，公司拥有全球员工4300余人，累计服务客户1400余家，成功交付项目超5000个。我们始终坚持以客户为中心，致力于提供创新可靠的全球化CDMO解决方案，让好药更早惠及大众。免责声明：本文仅作者个人观点的表达，文中观点不代表博腾及其所属子公司立场，亦不对本文所提供信息做任何形式的保证。同时，本文不做治疗方案推荐，也不承担因使用或依赖本文信息所产生的任何直接或间接的后果。如需获得治疗方案指导，请前往正规医院就诊。

2026-05-28

·BioSpace

Anaveon Reports Clinical Benefit of ANV600 in the EXPAND-1 Phase 1 Clinical Trial at ASCO 2026 and Actively Seeks Partners for its Legacy Oncology Portfolio

BASEL, Switzerland, May 28, 2026 (GLOBE NEWSWIRE) -- Anaveon, a late-stage preclinical biotechnology company focused on reprogramming the immune system for the treatment of autoimmune and inflammatory diseases, today announced that new clinical data from its legacy oncology asset ANV600 (sunekafusp alpha) will be presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. Following its strategic pivot to immunology, Anaveon is actively seeking global development and commercialization partners for its oncology portfolio to maximize the potential of these highly differentiated assets. ANV600 is a first-in-class, non-blocking PD-1-targeted IL-2R-βγ agonist designed to selectively expand tumor-reactive PD-1 + CD8 + effector T cells while reducing the toxicities historically associated with IL-2 therapy. It is compatible with existing Check Point Inhibitors (CPI) and is positioned for use in CPI-resistant and CPI-relapsed patients. Key results from the EXPAND-1 Phase 1 study will be highlighted in the poster: The encouraging preliminary antitumor activity observed with ANV600 should be investigated further through additional clinical studies with larger patient populations, ANV600 is well tolerated as a monotherapy and in combination with pembrolizumab, A complete response (CR) was observed in a patient with NSCLC (non-small cell lung cancer) previously progressing on CPI and treated with ANV600 monotherapy at 120 µg/kg Q2W. Partial responses (PRs) were reported for two patients treated respectively with 30 µg/kg and 60 µg/kg ANV600 Q2W in combination with pembrolizumab Q3W, Patients experienced target lesion shrinkage in 29% of patients receiving ANV600 monotherapy and 24% of patients receiving ANV600 plus pembrolizumab, Disease control defined as Complete Response, Partial Response, or Stable Disease observed in 42% of patients treated with ANV600 monotherapy and 59% of the patients receiving ANV600 and Pembrolizumab, Recommended Phase 2 dose of 90 µg/kg weekly for 4 weeks followed by 150 µg/kg Q2W established, Patients Treatment with ANV600 resulted in higher absolute counts of CD8 + T cells and NK cells over regulatory T cells. “Patients with advanced solid tumors treated with ANV600 derived meaningful clinical benefit, with approximately 24% of patients achieving a Complete Response, Partial Response or durable Stable Disease maintained for at least 18 weeks (≥3 tumor assessments),” said Prof. Dr. med. Markus Jörger of Health Ostschweiz (HOCH) in St. Gallen (Switzerland). “The trial provided a valuable treatment option for patients whose disease had progressed beyond available therapies. ANV600 demonstrated a promising safety-efficacy profile, together with compelling proof-of-mechanism in patients with advanced solid tumors.” ASCO Annual Meeting abstracts may be accessed online via . Presentation Details: Title: Safety, PK/PD, and efficacy results from Expand-1: A phase 1 dose escalation study of the novel PD-1 targeted IL-2R-βγ agonist sunekafusp alpha (ANV600) as a single agent and in combination with pembrolizumab in patients with advanced solid tumors. First Author: Markus Joerger Abstract number: 2587 Session Title: Development Therapeutics- Immunotherapy Poster board: 377 Location, Date and Time: Hall A, May 30, 2026, 1:30 to 4:30 pm, CDT “With established clinical benefits and strong interest from current clinical investigators, we believe that ANV600 is ideally suited for a partner with the resources and expertise to bring it forward in CPI-resistant NSCLC and other immuno-oncology indications,” added Thaminda Ramanayake , Chief Executive Officer of Anaveon . Anaveon’s proprietary oncology product portfolio is built around a non-blocking PD-1 targeted cytokine platform. This highly selective “cis-signaling” proximity-activated delivery of cytokines is precise and combinable with Check Point Inhibitors. In addition to ANV600, the platform includes ANV700, a preclinical proximity-activated PD-1-targeted IL-21 fusion protein with potential for synergistic effects when combined with IL-2-based approaches and another undisclosed preclinical program. Included in the oncology portfolio is ANV419, an earlier generation (non-PD-1-targeted) IL-2/anti-IL-2 fusion protein with demonstrated safety in prior clinical studies. The company is now prioritizing its core immunology pipeline and is open to various partnering structures (license, co-development, or acquisition) for the oncology platform and portfolio. For partnering inquiries, please, contact: collaborations@anaveon.com . Media contact: Benz Advisory Beatrix Benz Email: beatrix.benz@anaveon.com Tel: +41 79 256 77 73 About Anaveon: Anaveon AG is a late-stage preclinical biotechnology company headquartered in Basel, Switzerland. The company is dedicated to transforming lives by precisely modulating the immune system to address high unmet needs in autoimmune diseases and inflammatory disorders. Our therapeutics target central regulatory nodes of the immune system to selectively eliminate or reprogram pathogenic immune cells and restore durable immune balance. Anaveon is backed by Syncona, Forbion, Blue Owl, Novartis Venture Fund, Pfizer Ventures and Pontifax. About ANV600: ANV600 is a novel PD-1–targeted IL-2R-βγ agonist that binds PD-1 on a unique non-blocking epitope, distinct from that targeted by pembrolizumab and other PD-1 checkpoint inhibitors. It is designed to preferentially stimulate PD-1⁺ CD8⁺ T cells with a pre-exhausted, cytotoxic phenotype, aiming to activate tumor antigen-experienced T cells within the tumor microenvironment. This targeted, non-blocking PD-1 approach may reduce IL-2–related toxicities, enhance tumor selectivity, and potentiate responses in checkpoint-refractory tumors without compromising combination therapies. Find out more at > anaveon.com

2026-02-24

·递因递药

【免疫疗法】将IL2打乱重构：一种新型的PD-1靶向IL-2Rβγ激动剂ANV600

白介素-2（IL-2）在抗肿瘤免疫中具有关键作用，但其临床应用受限于系统性毒性及对调节性T细胞（Treg）的非选择性激活。近日，Anaveon公司在《Journal for ImmunoTherapy of Cancer》发表了其首创（First-in-Class）分子ANV600的研究数据。该分子是在ANV419的基础上，通过增加靶向PD-1非阻断位点，使其选择性激活IL-2Rβγ受体，实现了在肿瘤微环境中的精准免疫动员。一、传统IL-2疗法的问题不赘述。非选择性受体激活：传统IL-2优先结合表达IL-2Rα（CD25）的Treg细胞，产生免疫抑制效应，抵消抗肿瘤活性。严重的系统性毒性：药物结合血管内皮细胞引发毛细血管渗漏综合征（VLS），导致临床耐受剂量极低，难以维持有效的治疗窗口。二、 ANV600分子的结构设计与靶向策略 ANV600是一款双特异性抗体-细胞因子融合蛋白，其核心设计是通过蛋白质工程实现“顺式（cis）”激活，即药物分子同时结合同一细胞表面的PD-1和IL-2受体。 1. PD-1靶向性：ANV600的抗PD-1臂以高亲和力结合人PD-1（KD 5.0E-10）。其结合表位与帕博利珠单抗（Pembrolizumab）及纳武利尤单抗（Nivolumab）不产生空间竞争，支持三方同时结合。 2. 受体选择性：ANV600的IL2来自ANV419，利用一种巧妙的打乱重构的设计达到IL2受体选择性。简单说，将IL2 从K96和N97（按照前体序列编码）之间截开，创造一个新的N端和C端，同时将原N端P22和和C端T153连接，形成一个具有相同IL2结构的重组分子。将该重组分子插入至抗IL-2 抗体轻链，使抗IL-2 抗体遮蔽与α受体的结合。 IL-2Rα (CD25)：由于抗IL-2抗体的空间屏蔽效应，ANV600对CD25几乎不表现出任何结合活性。 IL-2Rβ (CD122)：ANV600保留了对CD122的正常结合力，亲和力水平与天然IL-2基本相当（KD 0.322 nM）。 3. 体外激活效能：在PD-1阳性的T细胞中，ANV600诱导STAT5磷酸化的EC50值显著降低。与非靶向的IL-2Rβγ激动剂相比，其激活效能提高了约88倍，验证了PD-1靶向带来的精准激活优势。 ANV600通过PD-1锚定，实现IL-2信号在同一细胞内的“顺式激活（Cis-activation）”，在降低系统暴露量的同时显著提升局部信号强度。三、 ANV600体内药效学评估研究团队在多个同系肿瘤模型中评估了ANV600的单药及联合药效： 1. 单药治疗剂量：剂量设置：0.03 mg/kg、0.1 mg/kg及0.2 mg/kg。药效结果：在B16F10黑色素瘤及MC38结肠癌模型中，0.2 mg/kg（静脉注射，第0、3天给药）诱导了最强烈的肿瘤生长抑制（TGI）。在B16F10模型中，TGI显著优于相同剂量的非靶向对照物。 2. 联合用药增效：方案：ANV600 (0.2 mg/kg) 联合 PD-1抑制剂 (10 mg/kg，腹腔注射，第0、3、7天给药)。结果：在对PD-1单药不敏感的模型中，联合治疗组实现了几乎完全的肿瘤消退，其抗肿瘤反应呈现明显的加成或协同效应。 3. TILs重编程：流式细胞术显示，0.2 mg/kg剂量的ANV600能显著扩增肿瘤内的CD8+ T细胞（特别是Tcex和Tpex亚群），同时不引起Treg细胞的显著增加。四、肿瘤原位激活机制研究团队通过FTY720（一种抑制淋巴细胞从淋巴结流出的药物）封闭实验发现： ANV600的抗肿瘤效力主要驱动自肿瘤微环境内已存在的驻留T细胞。这意味着该药物能够有效逆转TME内的免疫耗竭状态，通过“唤醒”已存在的肿瘤特异性T细胞群，而非单纯依赖外周血免疫细胞的募集。五、安全性数据与临床转化1. 毒性监测：在临床前剂量强度试验中，ANV419 (与ANV600的IL2 端完全一样)在猴的最高剂量（0.3 mg/kg）下未引发明显的副作用，ANV600 在小鼠中给予0.2 mg/kg 剂量下也未观察到明显的体重减轻。体重：实验动物体重保持稳定，未出现类似传统IL-2导致的急性体重下降。血管损害：组织学检查未观察到肺水肿或血管渗漏综合征（VLS）的相关指征。目前，ANV600已正式进入临床评估阶段：试验编号：NCT06470763（EXPAND-1研究）研究设计：针对晚期实体瘤患者的Phase I/II期临床研究。主要终点：评估ANV600作为单药，以及与帕博利珠单抗（Pembrolizumab）联用的安全性、耐受性及剂量限制性毒性（DLT）。总结 ANV600的研究成果为克服IL-2类药物的剂量限制毒性提供了验证性路径。通过靶向PD-1非阻断表位的“顺式激活”策略，ANV600有望在PD-1治疗耐药的患者中提供全新的治疗方案，并与现有的免疫检查点疗法实现深度协同。风险提示：药物研发具有高风险性，临床试验结果存在不确定性。本文仅供科研及医疗专业人士参考，不作为临床诊疗依据。请患者及其家属理性看待研发进展，并遵医嘱进行治疗。参考文献： Patrizia Murer, et al.ANV600 is a novel PD-1 targeted IL-2Rβγ agonist that selectively expands tumor antigen-specific T cells and potentiates PD-1 checkpoint inhibitor therapy. JITC 2025. SITC 2024, Poster # 954.

100 项与 ANV-419 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
非小细胞肺癌	临床2期	西班牙	Vall d'Hebron Institut d'Oncologia	2025-01-15
宫颈癌	临床2期	西班牙	Vall d'Hebron Institut d'Oncologia	2025-01-15
晚期恶性实体瘤	临床2期	美国	Anaveon AG	2022-12-16
晚期恶性实体瘤	临床2期	法国	Anaveon AG	2022-12-16
晚期恶性实体瘤	临床2期	德国	Anaveon AG	2022-12-16
晚期恶性实体瘤	临床2期	意大利	Anaveon AG	2022-12-16
晚期恶性实体瘤	临床2期	西班牙	Anaveon AG	2022-12-16
皮肤黑色素瘤	临床2期	美国	Anaveon AG	2022-12-16
皮肤黑色素瘤	临床2期	法国	Anaveon AG	2022-12-16
皮肤黑色素瘤	临床2期	德国	Anaveon AG	2022-12-16

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05578872 (CTgov)	临床1/2期	皮肤黑色素瘤 \| 晚期恶性实体瘤 \| 转移性黑色素瘤 ... 更多	29	ANV419 (ANV419 Single Agent, Low Dose)	繭製鑰憲膚簾鬱顧繭簾 = 鬱衊網窪醖窪衊願餘壓衊製衊窪選製糧積鏇窪 (鹹憲鬱願膚齋襯觸鹹觸, 鬱簾窪鏇衊製齋積鏇製 ~ 膚觸鏇壓築蓋網網廠鏇) 更多	-	2025-08-26
				ANV419 (ANV419 Single Agent, High Dose)	繭製鑰憲膚簾鬱顧繭簾 = 願蓋獵齋膚鏇積鏇構壓衊製衊窪選製糧積鏇窪 (鹹憲鬱願膚齋襯觸鹹觸, 廠鑰醖衊廠夢醖選夢淵 ~ 網壓繭鹹壓製觸憲鹹齋) 更多
NCT04855929 (ANV419-001, Pubmed)	临床1期	晚期恶性实体瘤	-	ANV419	襯醖網窪簾窪糧繭積鏇(繭淵顧顧繭憲獵網襯構) = 糧簾夢簾範淵衊廠製淵蓋衊壓餘窪顧獵鑰廠鑰 (膚簾觸醖願憲壓觸鹹鏇 ) 更多	积极	2023-11-01
NCT04855929 (ANV419-001, Corporate Publications) 人工标引	临床1/2期	肿瘤	26	ANV-419 (Single patient cohort)	-	积极	2022-09-10
				ANV-419 (3+3 cohort Dose Expansion)	簾艱蓋壓齋襯憲製選齋(衊鹹獵顧艱淵製獵艱繭) = 淵繭廠糧鹹簾壓觸糧醖製壓衊壓繭襯膚構觸糧 (齋選遞鹽鏇範選糧範鏇 ) 更多
NCT04855929 (ANV419-001, AACR2022)	临床1/2期	肿瘤	-	ANV419	構鬱範襯顧夢網鹽憲願(築顧鹽選廠鹽顧衊廠糧) = 憲憲願糧壓鬱齋願艱繭淵網廠廠獵衊壓鏇壓壓 (夢壓衊鹹製鬱窪構鹽艱 ) 更多	-	2022-06-15
NCT04855929 (ANV419-001, ASCO2022) 人工标引	临床1/2期	HR阳性/HER2低表达实体瘤	13	ANV419	範鑰醖艱衊鏇膚鹹遞鏇(繭鬱製觸製衊衊願衊製) = 鏇範壓鬱鑰鹽窪襯廠糧遞鹹遞醖觸繭鑰繭顧蓋 (遞鑰構壓觸顧鹹壓窪遞 ) 更多	积极	2022-06-02
SITC2021	临床1期	-	2	ANV419 0.03 mg/kg	餘顧鬱鬱夢繭淵簾顧觸(艱繭艱積鏇蓋鹽觸鏇製) = mild systemic inflammatory response was observed at 0.3 mg/kg evidenced by a transient increase of CRP on days 4 and 19 廠願壓遞範範鑰觸繭鹽 (衊鹹範膚糧鹽簾獵蓋獵 ) 更多	积极	2021-11-10
				ANV419 0.1 mg/kg