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更新于：2025-12-24
Insulin (Oramed)
重组人胰岛素（Oramed）
更新于：2025-12-24
概要
基本信息
最高研发阶段申请上市 |
首次获批日期- |
最高研发阶段(中国)申请上市 |
特殊审评- |
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关联
19
项与 重组人胰岛素（Oramed） 相关的临床试验NCT06731075
A Double-Blinded, Placebo-controlled, Double Dummy, Multi-center Randomized, Phase 3 Study to Evaluate the Efficacy and Safety of ORMD-0801 in Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on One to Three Glucose-lowering Agents
ORA-013-3 is a randomized, controlled study to test the efficacy and safety of an oral capsule of ORMD-0801 at several doses in patients with Type 2 Diabetes Mellitus (T2DM) who have not responded well to other glucose-lowering medications. A total of three hundred subjects will be enrolled in this study and will be required to complete this thirty-four-week clinical trial.
开始日期2025-12-15 |
申办/合作机构 Oramed Ltd. [+1] |
CTR20244337
一项开放、随机、两周期、两交叉、评价人胰岛素肠溶胶囊在中国健康男性受试者中的药效动力学、药代动力学及相对生物有效性、相对生物利用度研究
主要目的：
本研究采用高胰岛素-正葡萄糖钳夹技术作为测试方法，对人胰岛素肠溶胶囊进行药效动力学研究，对比人胰岛素肠溶胶囊与人胰岛素注射液(天麦霖® R)的相对生物有效性。
次要目的：
对人胰岛素肠溶胶囊进行药代动力学研究，对比人胰岛素肠溶胶囊与人胰岛素注射液(天麦霖® R)的相对生物利用度。
开始日期2024-07-17 |
申办/合作机构 Israel Oramd Co Ltd [+3] |
NCT04817215
A Double-Blinded, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of ORMD-0801 in Uncontrolled Type 2 DM Subjects on Diet Control Alone, Metformin Monotherapy, or Two or Three Oral Glucose-lowering Agents
To compare the efficacy of ORMD-0801 to placebo in improving glycemic control as assessed by A1C in inadequately controlled T2DM subjects on diet control alone or on diet control and metformin monotherapy or two or three oral glucose-lowering agents.
To assess the safety of repeat administration of ORMD-0801 in inadequately controlled T2DM subjects on on diet control alone or on diet control and metformin monotherapy or two or three oral glucose-lowering agents.
To assess the safety of repeat administration of ORMD-0801 in inadequately controlled T2DM subjects on on diet control alone or on diet control and metformin monotherapy or two or three oral glucose-lowering agents.
开始日期2021-10-01 |
申办/合作机构 |
100 项与 重组人胰岛素（Oramed） 相关的临床结果
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100 项与 重组人胰岛素（Oramed） 相关的转化医学
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100 项与 重组人胰岛素（Oramed） 相关的专利（医药）
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5
项与 重组人胰岛素（Oramed） 相关的文献（医药）2025-12-01·DIABETES OBESITY & METABOLISM
Pharmacokinetics and pharmacodynamics of oral insulin (
ORMD
‐0801) in healthy subjects: A phase I study using hyperinsulinaemic‐euglycaemic clamp
Article
作者: Zhou, Yingxia ; Chen, Yufei ; Lu, Jiangjie ; Ning, Guang ; Lv, Qing ; Wang, Jiayi ; Wang, Weiqing ; Shi, Jia ; Zhou, Jie ; Gao, Ya ; Ma, Ming ; Zhang, Yifei ; Sheng, Haiyuan ; Shao, Ting ; Hu, Zhuomeng
Abstract:
Aims:
To characterise the pharmacokinetic (PK) and pharmacodynamic (PD) properties of an oral insulin formulation (ORMD‐0801) in healthy subjects.
Materials and Methods:
In this phase I hyperinsulinaemic‐euglycaemic clamp study with open‐label, randomised, crossover design, 20 healthy Chinese male subjects were randomised to receive either oral
ORMD
‐0801 (8 or 16 mg), followed by subcutaneous (
SC
) insulin (5
IU
, Tianmailin®) or vice versa.
PK
and
PD
parameters were evaluated by assessing changes in plasma insulin levels and glucose infusion rate (
GIR
) during an 11‐h clamp procedure.
Results:
For 16 mg oral versus SC insulin, maximum GIR (GIR
max)
was 3.87 ± 1.08 versus 3.51 ± 0.52 mg/kg/min, and area under the glucose infusion rate curve from 0 to 11 h (AUC
GIR0–11h
) was 26.98 ± 10.69 versus 23.74 ± 9.04 h·mg/kg/min. For 8 mg oral versus
SC
insulin, GIR
max
was 3.86 ± 1.25 versus 5.41 ± 3.05 mg/kg/min, and AUC
GIR0–11h
was 27.07 ± 8.43 versus 29.95 ± 7.70 h·mg/kg/min. SC‐equivalent doses were 6.53 ± 3.97 IU (16 mg) and 4.62 ± 1.13 IU (8 mg), respectively. PK analysis showed area under the insulin concentration–time curve from zero to infinite (AUC
Ins0‐∞
) of 5.47 ± 3.17 versus 7.50 ± 2.37 h·ng/mL for 16 mg oral versus SC insulin, and 4.86 ± 2.89 versus 7.85 ± 2.02 h·ng/
mL
for 8 mg oral versus
SC
insulin, with relative bioavailability of 0.53 ± 0.25% and 0.94 ± 0.77%.
Conclusions:
This study comprehensively describes the PK/PD characteristics of ORMD‐0801 in healthy subjects and provides a basis for future clinical trials.
2024-01-01·Gastro hep advances
Oral Insulin Alleviates Liver Fibrosis and Reduces Liver Steatosis in Patients With Metabolic Dysfunction-associated Steatohepatitis and Type 2 Diabetes: Results of Phase II Randomized, Placebo-controlled Feasibility Clinical Trial
Article
作者: Lopez, Oliver ; Katchman, Helena ; Kidron, Miriam ; Neutel, Joel ; Kolben, Yotam ; Ishay, Yuval ; Gelman, Ram ; Mohseni, Rizwana ; Ilan, Yaron ; Arbib, Orly Sneh
Background and Aims:
Metabolic dysfunction-associated steatohepatitis is an advanced form of nonalcoholic fatty liver disease and a leading cause of end-stage liver disease and transplantation. Insulin resistance and inflammation underlie the pathogenesis of the disease.
Methods:
This double-blind, randomized, placebo-controlled, multicenter feasibility clinical trial aimed to determine the safety of oral 8 mg insulin in patients with metabolic dysfunction-associated steatohepatitis and type 2 diabetes mellitus. Patients were treated twice daily for 12 weeks with an 8 mg insulin (n = 21) or placebo (n = 11) capsule. Safety was monitored throughout the study. MRI-proton density fat fraction assessed liver fat content, and Fibroscan® measured liver fibrosis and steatosis levels at screening and after 12 weeks of treatment.
Results:
No severe drug-related adverse events were reported during the study. After 12 weeks of treatment, mean percent reductions in whole-liver (-11.2% vs -6.5%, respectively) and liver segment 3 (-11.7% vs +0.1%, respectively) fat content was higher in the insulin than in the placebo arm. Patients receiving insulin showed a median -1.2 kPa and -21.0 dB/m reduction from baseline fibrosis and steatosis levels, respectively, while placebo-treated patients showed median increases of 0.3 kPa and 13.0 dB/m, respectively. At Week 12, oral insulin was associated with a mean of 0.27% reduction and placebo with a 0.23% increase from baseline hemoglobin A1c levels. Mean percent changes from baseline alanine aminotransferase, and aspartate aminotransferase levels were -10% and -0.8%, respectively, in the oral insulin and 3.0% and 13.4%, in the placebo arm.
Conclusion:
The results of this feasibility study support the safety and potential therapeutic effect of orally delivered insulin on liver fibrosis, fat accumulation, and inflammatory processes (NIH Clinical Trials No. NCT04618744).
2023-04-01·Diabetes, obesity & metabolism
Oral insulin (
ORMD
‐0801) in type 2 diabetes mellitus: A
dose‐finding 12‐week
randomized
placebo‐controlled
study
Article
作者: Neutel, Joel ; Kidron, Miriam ; Homer, Kenneth ; Fleming, Alexander ; Eldor, Roy ; Rosenstock, Julio ; Francis, Bruce H.
Abstract:
Aims:
To assess the safety and efficacy of multiple daily doses of oral insulin (ORMD‐0801) in subjects with type 2 diabetes (T2DM) over 12 weeks.
Materials and Methods:
Participants with T2DM on metformin or combination oral therapy with glycated haemoglobin (HbA1c) levels ≥ 7.5% (58 mmol/mol) were randomized to receive ORMD‐0801 8 mg or 16 mg once (QD) or twice (BID) daily, or 32 mg QD, BID or three times daily (TID) over a 12‐week period.
Results:
A total of 373 subjects were randomized to active treatment or placebo (~60% male, age ~ 56 years, HbA1c 9%‐9.8%; 75‐84 mmol/mol). Placebo‐adjusted HbA1c changes from baseline to Week 12 were observed with ORMD‐0801 8 mg BID (−7.15 ± 3.57 mmol/mol [−0.65% ± 0.33%];
P
= 0.046). However, a significant site interaction was observed in two sites. After excluding these, HbA1c reduction was observed with 8 mg QD (−0.81 ± 0.37%; −8.89 ± 4.01 mmol/mol;
P
= 0.028, n = 15), 8 mg BID (−0.82 ± 0.37%; −8.95 ± 4.08 mmol/mol;
P
= 0.029, n = 17), 32 mg QD (−0.54 ± 0.26%; −5.89 ± 2.78 mmol/mol;
P
= 0.036, n = 69) and 32 mg BID (−0.53 ± 0.26%; −5.80 ± 2.83 mmol/mol;
P
= 0.042, n = 68). No effect was observed with 16 mg QD (0.25 ± 0.37%; 2.76 ± 3.99 mmol/mol;
P
= 0.48, n = 18), 16 mg BID (−0.36 ± 0.40%; −3.97 ±
P
= 0.36, n = 15) or 32 mg TID (−0.45 ± 0.27%, −4.89 ± 2.90 mmol/mol;
P
= 0.093, n = 69). Continuous glucose monitor and serum glucose measurements showed similar trends but were not significant. ORMD‐0801 was safe, well tolerated and not associated with weight gain or hypoglycaemia.
Conclusions:
Oral insulin (ORMD‐0801) induced greater reductions in HbA1c when compared to placebo, and was safe and well tolerated in individuals with uncontrolled T2DM. The efficacy and safety findings support continued development of the 8‐mg dose at bedtime, which is currently being evaluated in two Phase 3 trials.
76
项与 重组人胰岛素（Oramed） 相关的新闻（医药）2025-12-02
·药事纵横
将肽类和蛋白质类药物从注射给药转变为口服给药，是制药领域百年来的梦想与挑战。截至今日，我们见证了两个标志性分子的截然不同的命运：诺和诺德（Novo Nordisk）的口服司美格鲁肽（Semaglutide,商品名Rybelsus®）作为首个口服GLP-1受体激动剂（GLP-1RA）在全球范围内成功商业化，而口服胰岛素在历经无数次尝试后，其领跑者如Oramed公司的ORMD-0801和诺和诺德早期的OI338GT项目均以失败告终。到底什么原因造成这一“冰火两重天”局面？
1.口服司美格鲁肽的成功之路——技术、数据与策略的完美结合
口服司美格鲁肽于2019年获得美国FDA批准，并于2024年1月在中国获批上市。它的成功并非偶然，而是建立在三大支柱之上：革命性的递送技术、扎实的临床证据以及清晰的商业化路径。
1.1核心技术突破：SNAC平台克服口服肽类药物天堑
肽类药物口服给药面临两大核心障碍：胃肠道中蛋白酶的快速降解和肠道上皮细胞的低通透性。诺和诺德通过其专有的Eligen®技术，特别是核心赋形剂SNAC（SodiumN-(8-[2-hydroxybenzoyl]amino)caprylate，沙卡布若钠），巧妙地解决了这些问题。
图1 口服司美格鲁肽的作用模式（参考1）
SNAC的作用机制是多方面的，堪称“贴身保镖”：
局部环境改造与保护：当药片在胃中崩解时，SNAC能够瞬时提高胃部局部pH值，从而抑制胃蛋白酶的活性，保护司美格鲁肽免于被降解。
促进跨细胞吸收：SNAC是一种吸收促进剂，它能与司美格鲁肽分子发生非共价的疏水相互作用，增加其脂溶性。这使得药物分子能够更容易地以“跨细胞”途径（transcellular pathway）穿过胃上皮细胞膜，进入血液循环。
增加细胞间通透性：SNAC还能暂时性地影响细胞间的紧密连接，增加胃黏膜的通透性，为药物提供一条“旁细胞”吸收（paracellular pathway）的额外通道。
正是SNAC这一创新性的单一分子解决方案，取代了传统“肠溶包衣+蛋白酶抑制剂+渗透增强剂”的复杂组合，高效地将口服司美格鲁肽的生物利用度提升至一个虽低（约1%）但稳定、可预测且在临床上有效的水平，这是其成功的技术基石。
图2口服司美格鲁肽与SNAC共配制剂的吸收机制示意图。本示意图展示了以片剂形式存在的口服司美格鲁肽与SNAC共配制剂在胃中溶解和吸收的过程。当片剂在胃中崩解时，司美格鲁肽和SNAC被释放出来。SNAC发挥局部缓冲作用，图中以片剂周围的紫色区域表示。该缓冲作用保护司美格鲁肽免受胃蛋白酶（一种胃酶）的降解。由于在胃中避免了胃蛋白酶诱导的肽类降解，司美格鲁肽在通过跨细胞途径穿越胃粘膜的过程中，与SNAC分子保持微弱且非共价的结合状态。一旦SNAC和司美格鲁肽进入体循环，两者便会解离。（参考2）
1.2强大的临床证据：PIONEER项目构建的循证金字塔
诺和诺德为口服司美格鲁肽设计了规模宏大的PIONEER全球III期临床试验项目，该项目包含超过10个独立的临床试验，入组了近万名2型糖尿病患者，全面评估了其疗效和安全性。
卓越的疗效数据：
强效降糖与减重：PIONEER系列研究一致证明，口服司美格鲁肽在降糖和减重方面表现优异。例如，研究显示14mg、25mg和50mg剂量组的糖化血红蛋白（HbA1c）分别降低1.5%、1.9%和2.2%，体重分别减轻4.5kg、7.0kg和9.2kg。在中国患者亚组的PIONEER11研究中，HbA1c降幅高达1.6%，达标率（<7%）接近92.3%，效果显著。更高剂量的50mg在OASIS1试验中，68周可使体重平均降低17.4%。
心血管安全性得到证实：PIONEER6心血管结局试验（CVOT）表明，口服司美格鲁肽的心血管风险特征不劣于安慰剂。而司美格鲁肽注射剂在SELECT试验中已证明能显著降低主要不良心血管事件（MACE）风险，为整个产品家族提供了强大的心血管获益证据。
图3 PIONEER系列试验中口服司美格鲁肽与对照药物相比的HbA1c和体重自基线变化情况（参考1）
清晰且可管理的安全性特征：
PIONEER项目的数据显示，口服司美格鲁肽最常见的不良反应是胃肠道事件（如恶心、腹泻、呕吐），这些事件大多为轻至中度，且通常具有自限性，在治疗初期和剂量递增期更为常见。这一安全性特征与GLP-1RA类药物的已知情况相符，易于临床管理。其免疫原性风险低，临床试验中未观察到有临床意义的中和抗体。
这一系列设计严谨、数据扎实的临床试验，为监管机构的审批提供了无可辩驳的证据，也为上市后的市场推广奠定了坚实的基础。
1.3精准的监管与市场准入策略
诺和诺德凭借充分的临床前和临床数据，成功推动了口服司美格鲁肽的全球监管审批。
监管审批：FDA于2019年9月率先批准其上市。其后，诺和诺德积极在中国递交申请，并于2024年1月获得国家药品监督管理局（NMPA）的批准。在FDA的审评过程中，尽管其注射剂型的顾问委员会曾对糖尿病视网膜病变的风险表示担忧，但最终以16票赞成、0票反对的压倒性结果支持批准，认为通过标签说明即可管理该风险这为口服剂型的顺利审批扫清了部分障碍。
中国市场准入：司美格鲁肽注射剂型在2021年已被纳入中国国家医保药品目录（NRDL），为其市场渗透奠定了良好基础。口服剂型获批后，但凭借其作为“首款口服GLP-1”的独特性和巨大的临床需求，其市场前景被广泛看好。
综上，口服司美格鲁肽的成功，是创新制剂技术、大规模循证医学证据和成熟商业化运作三者协同作用的结果。
2.口服胰岛素的百年困局——难以逾越的技术与商业鸿沟
口服胰岛素的研发历史几乎与胰岛素发现的历史一样长，被誉为糖尿病治疗领域的“圣杯”。然而，一个世纪以来，尽管投入了巨大的研发资源，但截至2025年，全球仍无一款口服胰岛素成功商业化。其失败根源于多个相互关联且难以解决的深层次问题。
图4 口服胰岛素的努力（参考3）
2.1固若金汤的生理屏障：制剂技术的“阿喀琉斯之踵”
胰岛素是一种由51个氨基酸组成的蛋白质，其口服递送面临比司美格鲁肽（31个氨基酸的肽）更为严峻的挑战。
图5 口服胰岛素的挑战（参考4）
极端的胃肠道环境：胰岛素在胃的强酸环境下（pH1-2）极易变性失活，并迅速被胃蛋白酶降解。进入小肠后，又会面临胰蛋白酶等多种蛋白水解酶的攻击。
极低的肠道吸收效率：作为大分子蛋白质，胰岛素难以穿透由粘液层和紧密连接的肠上皮细胞构成的物理屏障。其生物利用度通常远低于1%，且个体间和个体内差异巨大。
递送技术策略的局限性：尽管研发人员尝试了各种技术，如肠溶包衣（保护药物通过胃部）、蛋白酶抑制剂（降低酶解）、纳米载体（如脂质体、纳米粒）和化学修饰等但这些策略往往“治标不治本”。它们或者保护不完全，或者增加了制剂的复杂性和生产成本，且始终未能将生物利用度提升至一个稳定且商业上可行的水平。
2.2临床试验的屡战屡败：从希望到失望的轮回
众多备受期待的口服胰岛素候选药物，最终都在关键的临床后期阶段折戟。
案例一：Oramed ORMD-0801的III期临床失败
作为近年来走得最远的口服胰岛素项目，Oramed公司的ORMD-0801采用了其POD™技术平台，结合了肠溶包衣、蛋白酶抑制剂和吸收促进剂。然而，在2023年初，Oramed宣布其两项关键性III期临床试验（如ORA-D-013-1）均未能达到其主要终点（在26周时降低HbA1c）和次要终点。这一决定性的失败，直接导致公司宣布停止该药物针对2型糖尿病的开发，给整个领域带来了沉重打击。值得注意的是，ORMD-0801的中国权益由天麦生物持有。在天麦生物于国内开展的III期临床试验中，其试验方案（例如入组患者的疾病程度、用药剂量等）与Oramed在海外失败的试验存在差异。因此，这款产品在中国的研发前景需要单独评估。
图6 单级与多级聚合物纳米颗粒的比较。基于共同辅料ERS-100，对HP55肠溶胶囊包裹的ERS-100纳米颗粒与PLGA-ERS纳米颗粒进行比较。（参考4）
案例二：诺和诺德OI338GT的商业考量
作为胰岛素领域的领导者，诺和诺德也曾大力投入口服胰岛素的研发。其项目OI338GT是一种口服长效基础胰岛素类似物。然而，在2016年，尽管项目已进入II期临床，诺和诺德却宣布终止该项目。官方给出的原因是“出于商业运作的考虑”。深入分析可知，这是因为要达到与注射胰岛素相当的疗效，所需的口服剂量巨大，导致生产成本（Cost of Goods）过高，完全不具备商业可行性。
这些失败案例揭示了一个残酷的现实：在现有技术条件下，口服胰岛素无法在疗效、稳定性、安全性和成本之间取得平衡。
2.3严峻的商业与监管挑战
高昂的制造成本与规模化生产难题：由于生物利用度极低，口服胰岛素需要数倍甚至数十倍于注射剂的原料药（API），这直接导致其生产成本居高不下。同时，复杂的制剂工艺（如纳米颗粒的制备）在大规模生产中难以保证批次间的质量均一性和稳定性，构成了巨大的制造挑战（CMC）。
缺乏明确的临床价值定位：在GLP-1RA等新型降糖药（特别是口服司美格鲁肽）可同时提供强效降糖、显著减重和心血管获益的多重优势背景下，一款仅仅是“无需注射”但价格昂贵、疗效可能不稳定的口服胰岛素，其临床价值主张（value proposition）变得愈发模糊和缺乏吸引力。
监管机构的审慎态度：尽管搜索结果中没有找到FDA或NMPA针对具体口服胰岛素项目终止的官方公开信函（表明终止决定多为企业主动行为），但可以预见，任何口服胰岛素要想获批，必须在大型临床试验中证明其与现有标准疗法（如注射胰岛素）相比至少达到非劣效性，同时还要有可接受的安全性、稳定性和成本效益。历史上的多次失败，使得监管机构对此类产品的审评必然会更加严格。
结论：殊途同归的启示与分野
口服司美格鲁肽的成功与口服胰岛素的百年困局，为大分子药物口服递送领域提供了教科书式的正反案例。两者的分野根植于技术、分子特性、临床价值与商业可行性的多重维度。
1. 技术平台是决胜基石：口服司美格鲁肽的胜利，本质上是其SNAC递送平台的胜利。该平台以相对普适、高效的单一分子方案，系统性地解决了肽类药物的胃肠道屏障，将生物利用度稳定在临床有效的水平。反观口服胰岛素，其固有的复杂结构与极端不稳定性，使得任何“打补丁”式的传统技术组合都难以在疗效、安全性与经济性之间取得平衡。
2. 分子特性与临床价值是根本驱动：司美格鲁肽分子本身经优化后稳定性高、半衰期长，其口服制剂更提供了“强效降糖+显著减重+心血管获益”的多重临床价值，超越了单纯的便利性。而口服胰岛素的核心价值仅在于“无针注射”，在现有技术下，其疗效的精准性与稳定性无法媲美注射剂，高昂的成本也使其在新型疗法面前缺乏竞争力。
3. 商业可行性是最终裁判：诺和诺德对口服胰岛素项目的果断放弃，清晰地表明：一项技术即便在科学上可行，若无法实现规模化、可负担的生产，也注定无法成为成功的商品。口服司美格鲁肽则证明了，通过革命性的制剂技术、严谨的临床开发与成熟的商业运作，攻克口服肽类药物的堡垒是完全可能的。
综上所述，口服司美格鲁肽的成功，为整个行业点亮了指路明灯。而口服胰岛素的破局，仍有待于未来出现能够系统性颠覆其递送难题的下一代技术。在此之前，它依然是制药科学领域那个充满诱惑却又遥不可及的“圣杯”。
参考文献
1.The development of oral semaglutide, an oral GLP‑1 analog, for the treatment of type 2 diabetes
2.Oral Semaglutide: A Review of the First Oral Glucagon-Like Peptide-1 Receptor Agonist
3.Oral Insulin: Challenges and Potential Solutions with a Case Study of Pharmaceutical Company Ventures
4.Critical updates on oral insulin drug delivery systems for type 2 diabetes mellitus
5.首个口服胰岛素在国内申报上市争议：海外临床失败，巨头纷纷被“劝退”
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2025-05-19
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摘要：胰高血糖素样肽-1（GLP-1）不仅是调控血糖的关键激素，近年研究发现其在脂质代谢中亦扮演重要角色。本文系统解析 GLP-1 通过抑制脂肪合成、促进脂肪分解与褐变、调节胆固醇代谢等多途径改善代谢紊乱的机制，综述其在肥胖、非酒精性脂肪肝（NAFLD）及动脉粥样硬化等疾病中的临床应用进展，并探讨 GLP-1/GIP双受体激动剂的潜在优势。研究表明，GLP-1及其类似物通过多靶点作用重塑脂质稳态，为代谢性疾病的治疗提供了新方向。一、GLP-1 的生理基础：从肠道到全身的代谢调控1.1分子结构与分泌特征GLP-1 是由肠道 L 细胞分泌的 30 氨基酸肽激素，主要以 GLP-1 (7-36) 酰胺形式发挥作用，半衰期仅 2-3 分钟，经二肽基肽酶-4（DPP-4）降解。其受体（GLP-1R）广泛分布于胰腺、肝脏、脂肪、心脏等组织，通过激活 cAMP 信号通路调控代谢（图 1）。1.2核心代谢调控途径胰腺：促进胰岛 β 细胞增殖，抑制凋亡，增强葡萄糖依赖性胰岛素分泌。肝脏：通过 AMPK/mTOR 通路抑制糖异生，激活自噬减少脂质堆积。脂肪组织：诱导白色脂肪褐变（WAT→BAT），增强能量消耗，抑制前脂肪细胞分化。中枢神经系统：作用于下丘脑，抑制食欲、延缓胃排空，调节能量平衡。二、GLP-1 与脂质代谢：多环节精准调控2.1抑制肝脏脂肪合成GLP-1 通过下调SREBP-1c、FAS等脂肪合成基因，减少甘油三酯（TG）生成。例如，利拉鲁肽（Lira）可通过抑制 SOCS-3 通路降低肝脏 TG 沉积，在高脂饮食小鼠模型中使肝脂肪含量减少 30%（表 1）。此外，GLP-1 通过激活 TFEB 通路增强自噬，促进脂质降解，改善肝 steatosis。表1：GLP-1 对肝脏脂质代谢的调控靶点通路 / 基因作用机制动物模型 / 临床研究AMPK/mTOR激活自噬，抑制脂质合成ob/ob 小鼠肝脂肪↓35%SREBP-1c下调脂肪酸合成酶（FAS）表达高脂饮食大鼠肝 TG↓28%TFEB增强自噬溶酶体通路HepG2 细胞脂滴↓40%2.2促进脂肪分解与褐变GLP-1 通过CREB-FNDC5 通路诱导鸢尾素（Irisin）分泌，促进白色脂肪褐变，增加解偶联蛋白 1（UCP1）表达，提升产热能力。在 3T3-L1 细胞模型中，GLP-1 可使褐色脂肪标志物 UCP1 表达增加 2 倍，同时激活 ATGL、HSL 等脂肪分解酶，加速脂肪酸氧化（图 2）。图 2：GLP-1 诱导白色脂肪褐变的分子机制2.3胆固醇代谢调控GLP-1 通过LXRα-ABCA1 通路促进胆固醇逆向转运，增加 apo AI 分泌，减少巨噬细胞泡沫化。Exendin-4 可使 ApoE⁻/⁻小鼠主动脉斑块面积减少 40%，同时上调 ABCA1 和 ABCG1 表达，抑制胆固醇在肝细胞和巨噬细胞内的堆积。三、临床应用：从代谢疾病到心血管保护3.1肥胖与代谢综合征GLP-1 类似物（如司美格鲁肽）通过抑制食欲、增强脂肪褐变，显著降低体重及体脂率。在 SURMOUNT-1 试验中，司美格鲁肽使肥胖患者体重下降 15.3%，同时改善血脂异常（TG↓24%、LDL-C↓17%）。其作用机制包括抑制下丘脑食欲中枢、激活棕色脂肪活性，且联合运动可进一步增强减脂效果（如运动 + 利拉鲁肽组腹部脂肪减少 6.1%，图 3）。图 3：GLP-1 类似物对肥胖患者体脂的影响（SURMOUNT-1 试验）3.2非酒精性脂肪肝（NAFLD）与 NASHGLP-1 通过多重机制改善肝脂肪代谢：减少脂质摄取：抑制 ACSL1、SREBP-1c，减少脂肪酸向肝脏转运。促进脂肪氧化：激活 PPARα 通路，增强线粒体 β 氧化。抗炎保肝：抑制 NLRP3 炎症小体，减轻肝纤维化。临床数据显示，司美格鲁肽治疗 48 周可使肝脂肪含量（LFC）减少 31%，且对 NASH 患者的肝纤维化改善率达 40%（表 2）。表 2：GLP-1 类似物在 NAFLD 中的疗效药物研究类型样本量治疗周期肝脂肪减少纤维化改善率利拉鲁肽随机对照试验10024 周↓28%-司美格鲁肽Ⅱ 期试验20048 周↓31%40%3.3动脉粥样硬化与心血管保护GLP-1 通过调节胆固醇逆转运及抗炎作用延缓动脉粥样硬化进程：减少泡沫细胞形成：通过 ABCA1 通路促进巨噬细胞胆固醇外流，抑制 LDL-C 氧化。稳定斑块：降低炎症因子（如 IL-6、TNF-α），提升斑块稳定性。尽管短期试验（如 EXSCEL）未显示显著斑块逆转，但长期数据提示 GLP-1 可降低心血管事件风险达 20%，尤其适用于合并糖尿病的动脉粥样硬化患者。四、新型疗法：GLP-1/GIP 双受体激动剂的突破4.1机制优势双激动剂（如 Tirzepatide）同时激活 GLP-1R 和 GIPR，较单药具备更强代谢调控能力：协同控糖：GIP 增强胰岛素分泌，弥补 GLP-1 单药在低血糖时的局限性。强化减脂：双重激活棕色脂肪活性，提升能量消耗效率。口服便利性：部分双激动剂（如口服剂型）克服注射依赖，提高依从性。4.2临床数据在 SURPASS 系列试验中，Tirzepatide 较安慰剂显著降低 HbA1c（-2.4% vs -0.9%）、体重（-11.3kg vs -3.1kg）及 LDL-C（-15.5%），且对 NAFLD 患者的肝脂肪减少效果优于单药（↓35% vs ↓28%）。此外，其心血管保护作用在 CVD-REAL 研究中显示可降低全因死亡率 15%。五、挑战与未来方向5.1现存挑战长期安全性：胃肠道副作用（如恶心、腹泻）发生率约 15-25%，需优化剂型减少局部刺激。成本与可及性：新型制剂价格高昂（如司美格鲁肽年费用约 $6000），限制低收入群体应用。耐药性争议：长期使用可能导致 GLP-1R 脱敏，部分患者用药 1 年后疗效衰减约 10-15%。5.2发展方向多靶点激动剂：开发 GLP-1R/GIPR/FGF21R 三靶点药物，如 MK-6024，通过协同调节脂质、糖代谢及能量平衡，提升疗效同时降低单药剂量依赖。临床前数据显示，三靶点激动剂可使小鼠肝脂肪减少 45%，优于双激动剂的 35%。口服制剂创新：利用纳米脂质载体技术开发口服 GLP-1 类似物（如 ORMD-0801），避免注射痛苦，目前 III 期数据显示其生物利用度达 18%，疗效与皮下注射相当。精准医疗策略：通过基因检测筛选 GLP-1R 高表达人群，例如携带 GLP-1R rs2268627 位点变异者，药物响应率提升 30%，避免无效用药。六、总结GLP-1 从传统降糖药物已拓展为代谢疾病的多面手，其通过调控肝脏脂肪合成、促进脂肪褐变及胆固醇逆转运，在肥胖、NAFLD 及心血管疾病中展现显著潜力。尽管面临安全性、成本及耐药性挑战，双靶点/多靶点激动剂的研发及口服剂型的突破，正推动领域向更高效、便捷的方向发展。未来，结合精准医疗与全球可及性策略，GLP-1 有望成为代谢健康领域的核心干预手段，为数千万患者带来新希望。识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。
临床结果
2025-04-11
Our analysis of February data reveals key trends in global clinical-stage biopharmaceutical financing. For contextual understanding, we recommend beginning with the following article.
Highlights of February 2025: Biopharmaceutical Clinical-Stage Drug Investment, Financing, and Collaboration Deals (1)
11. Kyorin and Cyrano Therapeutics Enter into an Option Agreement for the Development and Commercialization of CYR-064 in Japan
On February 14, 2025, Kyorin Pharmaceutical Co., Ltd. and Cyrano Therapeutics, Inc. announced the signing of an option agreement for the novel drug CYR-064, which is designed to treat hyposmia following viral infections. Under the terms of this agreement, Kyorin has obtained the rights to develop and commercialize CYR-064 in Japan and will pay an option fee. Once the option is exercised and a licensing agreement is signed, Kyorin will also provide Cyrano with an upfront payment, milestone payments based on development and commercialization progress, and royalties calculated as a percentage of net sales after the product is launched.
CYR-064 is a patented intranasal formulation of theophylline, a broad-spectrum phosphodiesterase inhibitor (PDEi), which increases intracellular cAMP levels by inhibiting cAMP degradation, thereby enhancing the excitability of olfactory neurons. This provides a potential therapeutic pathway for treating hyposmia following viral infections and other olfactory disorders. Currently, CYR-064 is undergoing a Phase II clinical trial in the United States, with trial data expected in the second half of 2025.
Guided by its long-term vision "Vision 110," Kyorin Pharmaceutical is committed to creating high-value new drugs that meet medical needs. By actively leveraging open innovation strategies, Kyorin plans to continuously launch new drugs. This collaboration with Cyrano is part of its strategic implementation, aiming to accelerate the development and commercialization of CYR-064 in the Japanese market to address unmet medical needs.
For the fiscal year ending in March 2025, this agreement is not expected to have a significant impact on Kyorin's business performance. However, with further development of CYR-064 and its potential market success, Kyorin anticipates positive financial returns in the coming years. Meanwhile, this collaboration also opens up new prospects for finding effective treatments for hyposmia following viral infections on a global scale.
12. Royalty Pharma Invests $250 Million to Support Biogen's Lupus Drug Litifilimab Development
Royalty Pharma has entered into a $250 million agreement with Biogen to support the development of Biogen's late-stage experimental lupus drug litifilimab. Under the terms of the agreement, Biogen will receive this amount over the next six quarters. In return, if the drug achieves specific regulatory milestones, Royalty Pharma will receive undisclosed milestone payments and a mid-single-digit royalty on global sales. This transaction not only enhances Royalty Pharma's product portfolio but also brings more opportunities for potential revenue.
Litifilimab is an anti-BDCA2 antibody currently in Phase III trials for systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). The drug has demonstrated significant reduction in skin disease activity in the Phase II LILAC study, showing effective relief of skin symptoms in CLE patients compared to the placebo group at the primary endpoint. If approved by 2030, litifilimab is projected to achieve up to $750 million in global sales. This potential allows Biogen to use the funds to further advance its development process.
Currently, the SLE market is dominated by generic drugs, with only a few targeted biologics approved by the U.S. Food and Drug Administration (FDA) in the past fifty years, such as GSK's Benlysta (belimumab) and AstraZeneca's Saphnelo (anifrolumab). In contrast, the CLE market is even more innovation-starved, with this form of lupus primarily affecting the skin, causing inflammation, rashes, and lesions. The successful development of litifilimab could change this status quo and provide new treatment options for patients.
13. Tivic Health Acquires Statera Biopharma's TLR5 Agonist Entolimod™ to Expand Its Therapeutic Pipeline
Tivic Health Systems, Inc. has announced the acquisition of global exclusive rights to the late-stage Toll-like receptor 5 (TLR5) agonist Entolimod™ from Statera Biopharma for the treatment of acute radiation syndrome (ARS). In addition, Tivic has obtained exclusive options for five additional indications and clinical uses of Entolimod and its derivative Entalasta™. This extensive licensing agreement transforms Tivic into a diversified therapeutic company with complementary bioelectronic and biologic candidates in its clinical pipeline.
As the lead candidate in the licensed portfolio, Entolimod is a TLR5 agonist specifically designed for the treatment of ARS. According to data from market research firm CoherentMI, the global ARS market was valued at $5.2 billion in 2024 and is projected to grow at a compound annual growth rate of 5% from 2024 to 2031. Entolimod and its immune-optimized derivative Entalasta have undergone over forty animal and human trials and received approximately $140 million in investment. The FDA has granted Entolimod Fast Track and Orphan Drug designations for the prevention or treatment of ARS and to prevent death following a potentially lethal dose of total-body ionizing radiation after a radiological disaster.
Animal studies for ARS have shown that a single dose of Entolimod administered 25 hours after exposure to a lethal level of radiation can triple survival rates. The drug is effective without additional supportive care, demonstrating gastrointestinal protective properties and no dose-limiting toxicity even at the highest doses. Other studies have also shown its potential in applications such as immunosenescence, lymphocyte exhaustion, neutropenia, vaccine enhancement, and chronic radiation syndrome.
Under the agreement, Tivic will initially pay Statera $1.2 million in equity consideration and $300,000 in cash for the use of Entolimod in treating ARS. Tivic has the option to add one or more indications and expand its licensing scope to Entolimod's derivative Entalasta by exercising the exclusive options granted in the agreement. Future potential payments will be royalty and milestone-driven, ensuring alignment with the clinical and commercial success of Entolimod and subsequent Entalasta. The agreement structure allows Tivic to strategically manage its investment while maximizing shareholder returns.
To establish Tivic's biopharmaceutical capabilities and advance the product candidates toward commercialization, some members of Statera's team will join Tivic. The transaction also includes exclusive rights and options to over sixty patents and pending patents, related proprietary technology, and ownership of previously manufactured and tested materials. Craft Capital Management LLC served as the sole investment banking firm in this deal. With these resources integrated, Tivic is steadily moving toward becoming a leading biotherapeutic company.
14. Oramed Pharmaceuticals Announces Formation of OraTech Pharmaceuticals to Accelerate Development and Commercialization of Oral Insulin
Oramed Pharmaceuticals Inc., a clinical-stage pharmaceutical company focused on the development of oral drug delivery platforms, recently announced that it will transfer its proprietary Protein Oral Delivery (POD™) technology to a new joint venture, OraTech Pharmaceuticals Inc., through a definitive agreement. This move is aimed at accelerating the development and commercialization of Oramed's oral insulin ORMD-0801 and other innovative oral drug delivery technologies based on the POD™ platform.
In this transaction, Oramed will transfer its proprietary oral insulin and POD™ technology, along with other pipeline assets, to OraTech. Oramed shareholders will receive a majority stake in the new entity, allowing them to directly participate in its future success. Additionally, under the terms of the agreement, Oramed and HTIT will jointly invest $75 million, with Oramed contributing $15 million and HTIT contributing $60 million. This funding will provide OraTech with the necessary resources to advance product development, commercialization, and clinical progress.
OraTech will leverage HTIT's expertise in capsule manufacturing and cost-effective production capabilities to establish a robust, reliable, and scalable supply chain to support clinical trials and commercial efforts. HTIT will also provide a supply agreement for the oral insulin capsules. Furthermore, OraTech plans to relaunch the pivotal Phase III clinical trial in the United States and advance the registration of oral insulin in the U.S. and other countries. In China, OraTech will receive royalties from the sales of oral insulin, while HTIT will be responsible for submitting marketing authorization applications and preparing for commercialization.
15. AdvanCell and Eli Lilly Expand Collaboration to Advance Cancer Targeted Alpha Therapy
On February 10, 2025, AdvanCell announced that its strategic partnership with Eli Lilly and Company has been further expanded. This collaboration aims to research and develop innovative treatments for various types of cancer. The partnership not only recognizes AdvanCell's leadership in the field of Pb-212 targeted alpha therapy but also lays the foundation for a long-term collaboration between the two companies.
Under the new cooperation agreement, both parties will utilize AdvanCell's proprietary Pb-212 production technology and radiopharmaceutical development infrastructure, as well as Eli Lilly's drug candidates and extensive drug development experience, to jointly advance the development of more targeted alpha radiopharmaceutical therapies and accelerate their clinical progress. AdvanCell's technological advantages and its infrastructure established in Australia to expedite early clinical trials enable it to quickly move novel radiotherapeutic drugs containing Pb-212 from the discovery phase to clinical trials.
AdvanCell is currently conducting a Phase I/II trial for ADVC001, a potentially best-in-class targeted alpha therapy for metastatic prostate cancer. The trial aims to assess the safety and efficacy of the Pb-212-based radiopharmaceutical therapy. The core product ADVC001 is designed to bind to PSMA (a cell surface target highly expressed in prostate cancer) and has demonstrated potential best-in-class characteristics in preclinical studies. This collaboration is expected to accelerate the development of ADVC001, bringing new hope to patients with prostate cancer.
As the partnership between AdvanCell and Eli Lilly continues to deepen, both parties are committed to achieving new breakthroughs in cancer treatment. By integrating their respective strengths and technologies, the two companies will not only accelerate the clinical progress of existing projects but also potentially open up new therapeutic pathways. For cancer patients who do not respond well to traditional therapies, targeted alpha therapy offers a more precise and less side-effect-prone treatment option. In the future, with the emergence of more research results, it is expected that more patients will benefit from this innovative cancer treatment method.
16. OliX and Eli Lilly Reach Global Licensing Agreement to Develop New Therapies for MASH and Other Cardiometabolic Indications
On February 10, 2025, OliX Pharmaceuticals announced a global licensing agreement with Eli Lilly and Company. This cooperation aims to jointly develop and commercialize OliX's OLX75016, a Phase I candidate drug primarily targeting metabolic-associated fatty liver hepatitis (MASH) and other cardiometabolic indications. Under the terms of the agreement, OliX will receive an upfront payment from Eli Lilly to support the ongoing Phase I clinical trial in Australia.
OLX75016 originates from robust targets identified through genome-wide association studies (GWAS), a method that can identify genomic variations in large populations. In preclinical studies, OliX has demonstrated the efficacy of OLX75016 in treating MASH, liver fibrosis, and other cardiometabolic indications. Currently, OliX is developing OLX75016 as a novel therapy for MASH with liver fibrosis and other cardiometabolic conditions.
OliX Pharmaceuticals is a clinical-stage pharmaceutical company focused on developing treatments for various diseases using its proprietary RNAi technology. The company's core RNAi platform—Asymmetric siRNA (asiRNA)—is a unique gene-silencing technology based on RNA interference (RNAi) and is considered one of the most effective gene-silencing technologies currently available. Using this proprietary asiRNA technology, OliX has developed cell-penetrating asiRNA (cp-asiRNA), a therapeutic RNAi platform that effectively targets diseases such as proliferative scar formation, dry and wet age-related macular degeneration (AMD), and subretinal fibrosis.
In addition to cp-asiRNA, OliX has also developed another therapeutic RNAi platform, GalNAc-asiRNA, specifically for targeting various liver diseases. This collaboration with Eli Lilly not only advances the development of OLX75016 but also further solidifies OliX's position in the biopharmaceutical field, demonstrating its commitment to addressing unmet medical needs through innovative technologies. As research and development progresses, it is anticipated that more new therapies based on these advanced technologies will emerge, bringing hope to patients worldwide.
17. Kineta Restructures Portfolio Ahead of Merger with TuHURA
Ahead of its merger with TuHURA Biosciences, Kineta has made significant adjustments to its portfolio. To streamline its investments, Kineta decided to sell its collaboration deals with Genentech and Merck & Co. to an investment company and transferred its pain treatment candidate drug KCP506 to Pacira Pharmaceuticals, while also terminating its cooperation agreement with GigaGen. TuHURA purchased Kineta for $15 million, with $5 million allocated to secure the exclusivity agreement. This acquisition enabled TuHURA to acquire Kineta's Phase II checkpoint inhibitor.
In 2018, Genentech paid Kineta a $5 million upfront payment to obtain the rights to a small molecule modulator and set milestone payments of up to $96 million. The collaboration was expanded in 2020 to support the early development phase of a pain treatment candidate drug. On the other hand, Kineta inherited a collaboration with Merck from its merger with Yumanity Therapeutics, which obtained a preclinical drug candidate for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia from Yumanity in 2020. In 2023, Kineta received a $5 million milestone payment from Merck, with up to $255 million still pending.
KCP506 is an α9α10 nicotinic acetylcholine receptor (nAChR) antagonist that Kineta is developing for the treatment of chronic neuropathic pain. Kineta initiated a Phase II trial for this drug. Subsequently, Kineta agreed to sell KCP506 to Pacira Pharmaceuticals for $450,000, marking the end of Kineta's further development of KCP506.
A subsidiary of HealthCare Royalty Partners, HCRX Investments Holdco, reached an agreement with Kineta covering Kineta's licensing deals with Genentech and Merck, as well as its role in an agreement with Fair Therapeutics related to cystic fibrosis. This move will help Kineta focus its resources on the development of other key projects.
Finally, Kineta decided to terminate its option and licensing agreement with GigaGen, which originally granted Kineta the rights to a CD27 drug program. By terminating this agreement, Kineta not only returned all rights to GigaGen but also waived its obligation to pay a $180,000 fee. This strategic retreat allows Kineta to concentrate more on the upcoming merger and the development of its core business.
18. Fosun Pharma and Dr. Reddy's Reach Licensing Agreement for HLX15 in Europe and the U.S.
On February 6, 2025, Fosun Pharma announced a licensing agreement with Dr. Reddy's Laboratories for HLX15, a biosimilar to daratumumab, an anti-CD38 monoclonal antibody under development. HLX15 is a recombinant human anti-CD38 monoclonal antibody injection intended for the treatment of multiple myeloma and other hematologic malignancies. Under the agreement, Dr. Reddy's will obtain exclusive commercialization rights to the drug in 43 countries and regions, including 42 European countries and the United States. The collaboration aims to expand the drug's market coverage and provide advanced biologics to more patients.
According to the terms of the agreement, Fosun Pharma will be responsible for the development, production, and commercial supply of HLX15 and may receive up to $131.6 million in funding from Dr. Reddy's, including a $33 million upfront payment and additional milestone payments. Additionally, Fosun Pharma will receive royalties based on annual net sales. This arrangement not only provides Fosun Pharma with the necessary cash flow to support its ongoing research and development but also enhances its competitiveness in the global market.
HLX15, as a biosimilar, primarily works by targeting and inhibiting the function of the CD38 protein to combat multiple myeloma. CD38 is a protein highly expressed on the surface of certain cancer cells, and monoclonal antibodies targeting it can effectively identify and destroy these cells while minimizing impact on normal tissues. Therefore, HLX15 is expected to become an important option for treating such diseases.
19. Relmada Therapeutics Acquires Potential Tourette Syndrome Therapy Sepranolone from Asarina Pharma AB
On February 6, 2025, Relmada Therapeutics announced the acquisition of Sepranolone from Asarina Pharma AB, a therapeutic asset for Tourette Syndrome (TS) and other compulsive-related disorders, ready to enter Phase IIb clinical trials. Sepranolone (isoallopregnanolone) is a first-in-class GABAA modulatory steroid antagonist (GAMSA) that selectively acts on the GABAA pathway, aiming to counteract the effects of allopregnanolone on TS and other compulsive disorders.
An open-label Phase IIa randomized study showed that Sepranolone has the potential to improve TS symptoms, as measured by changes in the Yale Global Tic Severity Scale (YGTSS). In the 12-week study, Sepranolone not only reduced the primary clinical endpoint of tic severity by 28% (p=0.051) compared to standard care alone but also achieved positive results in four key secondary endpoints, including a 69% improvement in quality of life, a 50% reduction in functional impairment, and a 44% reduction in premonitory urges. Additionally, the drug did not exhibit off-target central nervous system effects or systemic adverse effects, which is a significant advantage for central nervous system disorders requiring long-term use and potentially severe side effects.
Under the terms of the agreement, Relmada acquired global ownership of Sepranolone from Asarina Pharma AB for €3 million, completing the transaction through an asset purchase agreement. This acquisition reflects Relmada's mission to find solutions for refractory central nervous system diseases and its strategic goal of enhancing shareholder value by identifying and developing innovative compounds.
Relmada will continue to evaluate additional products and strategic opportunities and expects to update investors on the next steps for Sepranolone's development later in 2025. With further clinical data support, if Sepranolone successfully transitions to later-stage clinical trials and ultimately receives approval, it is expected to become one of the first-line treatments for Tourette Syndrome, bringing new hope to patients.
20. Acelyrin Terminates Izokibep Program, Affibody Regains Drug Development Rights
In 2021, Acelyrin acquired the license for izokibep with a $25 million upfront payment and committed to milestone payments of up to $280 million. Izokibep is an IL-17A inhibitor with a molecular weight only about one-eighth that of a typical antibody, exhibiting extremely high affinity for IL-17A and capable of specifically binding to both subunits of IL-17A as well as albumin in the serum. However, less than two years later, despite raising $540 million through an initial public offering to fund the late-stage trials of izokibep across multiple indications, Acelyrin ultimately decided to cease investment in the drug.
Izokibep achieved the primary endpoint in a Phase III clinical trial for the treatment of hidradenitis suppurativa (HS), demonstrating a 33% reduction in abscesses and inflammatory nodules by 75% or more in patients, compared to 21% in the placebo group. Despite these positive results, Acelyrin chose to discontinue investment in this indication. Additionally, after achieving success in psoriatic arthritis (PsA), Acelyrin also withdrew its investment, retaining only uveitis as the final active development area for izokibep. However, the Phase IIb/III trial in this area failed to meet its primary and secondary endpoints.
With Inmagene Biopharmaceuticals terminating the agreement covering Asian countries, including China and South Korea, the responsibility for izokibep will now fall entirely on Affibody in Sweden. Affibody's CEO, David Bejker, stated that he believes his company can better capitalize on the potential of izokibep than its former partner, particularly in the field of dermatology and for patients severely affected by hidradenitis suppurativa. This indicates Affibody's confidence in the potential of its product and its determination to regain control of the project.
21. Vanda Pharmaceuticals and AnaptysBio Reach Global Exclusive Licensing Agreement for IL-36R Antagonist Imsidolimab
On February 3, 2025, Vanda Pharmaceuticals and AnaptysBio announced a global exclusive licensing agreement for imsidolimab, an IL-36R antagonist monoclonal antibody. Imsidolimab has completed two pivotal global Phase III clinical trials for generalized pustular psoriasis (GPP) - GEMINI-1 and GEMINI-2, demonstrating good safety and efficacy. This drug balances the inflammatory response by inhibiting the function of the IL-36 receptor, which is particularly important for GPP patients caused by mutations in the IL36RN gene.
Under the terms of the agreement, Vanda will pay AnaptysBio a $10 million upfront payment and $5 million for existing drug supplies. Additionally, AnaptysBio will be eligible for up to $35 million in future regulatory approval and sales milestone payments, as well as a 10% royalty on global net sales. In this transaction, Vanda has obtained the global exclusive rights to develop, produce, and commercialize imsidolimab. These funds will support further research and development efforts to ensure that imsidolimab can reach the market as soon as possible.
In the Phase III clinical trial of GEMINI-1, 53% of patients receiving a 750 mg intravenous injection of imsidolimab achieved a GPP Physician's Global Assessment (GPPPGA) score of 0/1 (skin almost or completely clear) at week 4, compared to only 13% in the placebo group (p=0.0131). In the subsequent GEMINI-2 trial, all patients in the maintenance dose treatment group maintained a GPPPGA score of 0/1 without relapse, while 63% of patients in the placebo group experienced disease worsening. These results indicate that imsidolimab has significant efficacy for GPP.
Summary
The clinical-stage drug investment, financing, and collaboration transactions in February 2025 revealed several trends: First, capital continues to be optimistic about innovative drugs, especially those with breakthrough therapeutic potential, and is willing to invest substantial funds to support research and development. Second, antibody-drug conjugates (ADCs) have become one of the key areas of collaboration, demonstrating the global popularity of this technology platform. Lastly, Chinese pharmaceutical companies are not only seeking growth opportunities in the domestic market but also actively expanding into international markets, accelerating the global layout and commercialization of new drugs through licensing deals and other means. These dynamics indicate that, despite the many challenges facing the pharmaceutical industry, companies are actively exploring new development paths through capital injection and technological collaboration, aiming to gain a favorable position in global competition.
How to get the latest progress on drug deals?
If you would like to access the latest transaction event information, you can click on the 'Deal' module from the homepage of the Synapse database. Within the Deal module, you can search for global pharmaceutical transaction information using labels such as Drugs, Organization, Target, Drug Type, Deal Date.
Furthermore, you can obtain the original link to the transaction coverage by clicking on the "Deal Name."
In the analysis view, you can see the most active assignors, assignees, popular targets, and other dimensions of analysis, as well as the distribution of research and development statuses at the time of the transaction, to help you better understand the search results.
The Synapse database also supports the ability to view current transactions from the dimension of "drugs" (by selecting "drugs" from the "Adjust Dimension" dropdown menu above). Targeting transactions involving renowned pharmaceutical companies that are of interest to the industry, such as Merck, Roche, etc., Synapse has identified a group of "leading companies" through drugs that have achieved global sales exceeding 1 billion US dollars in 2022. Transactions involving drugs from these leading companies can be filtered by clicking on the "Leading Company" tag on the left-hand side.
In addition to the drug transaction module, you can also view related transaction history on the drug detail page and the institution detail page.
Click on the image below to explore new pharmaceutical funding transactions!
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| 2型糖尿病 | 申请上市 | 中国 | 2023-04-25 | |
| 纤维化 | 临床2期 | 以色列 | 2018-09-20 | |
| 代谢功能障碍相关脂肪性肝炎 | 临床2期 | 以色列 | 2018-09-20 | |
| 1型糖尿病 | 临床2期 | 以色列 | 2008-07-01 | |
| 糖尿病 | 临床1期 | 中国 | 2019-09-03 |
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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 |
|---|
临床2期 | 32 | Placebo (Placebo) | 鑰艱鬱鏇鑰選範鏇網夢 = 衊淵糧鑰憲簾淵遞鑰窪 繭餘積艱願齋構鹽壓憲 (獵鹽顧觸蓋鏇壓廠製糧, 觸淵淵糧餘糧築繭繭願 ~ 繭襯鏇選顧夢襯廠衊顧) 更多 | - | 2024-08-07 | ||
(ORMD-0801 (Insulin) Capsule 8 mg BD) | 鑰艱鬱鏇鑰選範鏇網夢 = 鑰膚廠願廠廠夢範鑰艱 繭餘積艱願齋構鹽壓憲 (獵鹽顧觸蓋鏇壓廠製糧, 糧糧選鹽鑰憲獵膚繭鬱 ~ 鏇遞願膚簾襯選網遞壓) 更多 | ||||||
临床2期 | 49 | Placebo (Placebo) | 鹹衊憲蓋淵醖構壓壓廠(夢遞鹽醖鹽鬱獵築齋夢) = 膚醖構淵積鏇獵製衊襯 鹹鏇鏇蓋繭壓廠衊蓋壓 (襯蓋顧範衊範醖齋願膚, 922.89) 更多 | - | 2024-05-07 | ||
(ORMD-0801) | 鹹衊憲蓋淵醖構壓壓廠(夢遞鹽醖鹽鬱獵築齋夢) = 鏇鑰醖鏇範餘遞鏇齋製 鹹鏇鏇蓋繭壓廠衊蓋壓 (襯蓋顧範衊範醖齋願膚, 830.29) 更多 | ||||||
临床2期 | 7 | 齋蓋獵網鬱選衊遞衊襯 = 鑰膚窪網簾憲簾餘窪衊 憲醖夢餘醖網襯憲築鑰 (獵顧觸襯窪壓繭糧構簾, 襯淵襯淵製襯範範齋鑰 ~ 齋顧壓醖餘鹹製膚餘簾) 更多 | - | 2024-03-29 | |||
临床2期 | - | 窪築顧鬱簾襯窪齋鹹構(範觸廠鏇鏇窪壓製網構) = 顧艱簾淵艱構積構製糧 範願鑰獵繭願積鏇網鏇 (簾襯遞淵築淵膚壓餘餘 ) 更多 | 积极 | 2024-01-01 | |||
Placebo | 窪築顧鬱簾襯窪齋鹹構(範觸廠鏇鏇窪壓製網構) = 夢選醖構齋積壓鏇醖觸 範願鑰獵繭願積鏇網鏇 (簾襯遞淵築淵膚壓餘餘 ) 更多 | ||||||
临床2期 | - | 醖廠壓積築艱選窪糧網(醖簾願壓繭鏇鹽繭淵築) = 壓齋廠築壓簾壓廠淵艱 廠襯願廠簾鏇製窪膚淵 (糧網夢顧獵醖鹹淵積醖, 30.4) 更多 | 积极 | 2023-10-04 | |||
Placebo | 醖廠壓積築艱選窪糧網(醖簾願壓繭鏇鹽繭淵築) = 觸網鹹繭淵觸鹽夢膚壓 廠襯願廠簾鏇製窪膚淵 (糧網夢顧獵醖鹹淵積醖, 26.7) 更多 | ||||||
临床2期 | 32 | 鹽製鏇糧選觸鏇選襯餘(遞鏇選淵鑰衊願襯範簾) = Primary objective of safety met with no serious adverse events and no difference in the incidence rate of adverse events between ORMD-0801 and placebo. 艱壓衊繭構鹹簾鑰鬱衊 (遞憲簾製選糧製積膚蓋 ) | 积极 | 2022-11-17 | |||
Placebo | |||||||
临床2期 | 30 | Placebo (Baseline) | 糧鹹憲構觸鬱鹹膚蓋獵(襯構築製廠選觸壓蓋顧) = 衊鑰艱艱齋積鑰選鏇積 積膚鏇襯積網醖廠鹽衊 (遞壓製襯簾遞築餘繭齋, 2.489) 更多 | - | 2022-06-02 | ||
(Treatment A) | 糧鹹憲構觸鬱鹹膚蓋獵(襯構築製廠選觸壓蓋顧) = 鹽簾鑰鹽窪觸範膚繭艱 積膚鏇襯積網醖廠鹽衊 (遞壓製襯簾遞築餘繭齋, 2.486) 更多 | ||||||
临床2期 | 188 | 觸鏇壓膚醖醖願鑰鏇夢(糧壓蓋獵窪積醖顧願範) = 鏇廠鑰鏇願壓鏇鑰繭範 鏇鹽選鏇餘膚壓繭簾網 (衊淵築選繭鹹積齋糧構, 23.5) 更多 | 积极 | 2021-11-01 | |||
Placebo | 觸鏇壓膚醖醖願鑰鏇夢(糧壓蓋獵窪積醖顧願範) = 網膚遞製糧願蓋窪繭蓋 鏇鹽選鏇餘膚壓繭簾網 (衊淵築選繭鹹積齋糧構, 26.1) 更多 | ||||||
临床2期 | 10 | Oral Insulin | 網壓鬱艱蓋膚繭膚襯網(艱鏇艱選鑰網淵構鑰網) = 顧範鏇獵襯鬱蓋願膚範 衊衊鏇積範窪齋鏇廠廠 (鏇壓網糧襯壓夢鑰鹽淵, 7.2) 更多 | - | 2021-09-23 | ||
临床2期 | 8 | 鑰衊襯襯鑰廠鹹願壓淵(夢遞廠糧艱膚廠鬱選糧) = The 12-week ORMD-0801 treatment proved safe and tolerable in all patients, with no serious or severe adverse events recorded throughout the study period. 築壓餘醖蓋憲窪鬱簾願 (積窪構襯構遞繭築鑰積 ) | 积极 | 2020-09-24 |
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