As obesity rates continue to rise globally, combination therapies are being developed for their pronounced and sustained weight loss effects. CagriSema is a fixed-ratio combination of the long-acting GLP-1R agonist semaglutide and the calcitonin (CTR)/amylin receptor (AMYR) agonist cagrilintide that shows greater efficacy for weight loss compared to GLP-1R and CTR/AMYR mono-agonists alone. However, knowledge of the neural sites capable of producing potentiated effects as a result of GLP-1R/CTR/AMY co-agonism remains incomplete. In this study, we investigate the laterodorsal tegmental nucleus (LDTg) as a central site of integration for GLP-1R and CTR/AMYR signaling, and explore the effect of co-agonism in this nucleus on feeding behavior. We first performed fluorescence in situ hybridization (FISH) to show that glp-1r- and ctr-expressing neurons comprise largely distinct populations within the LDTg, supporting a model where LDTg GLP-1R and CTR/AMYR agonists reduce feeding via engagement of distinct complementary cells in the LDTg. We also showed that co-administration of GLP-1R and CTR/AMYR agonists into the LDTg resulted in a greater suppression of food intake and reduction in body weight compared to either treatment alone. Finally, using an operant model, we found that this combinatorial treatment significantly reduced motivation to self-administer a highly palatable food reward. Overall, intra-LDTg co-agonism of GLP-1Rs and CTR/AMYRs produced a greater suppressive effect on homeostatic and motivational aspects of feeding behavior than monotherapy alone. These results highlight the LDTg as a previously undescribed central site with potential clinical relevance for the development of dual GLP-1R and CTR/AMYR pharmacotherapies to combat obesity.

2026-09-29·ENDOCRINOLOGY

GHRH and GLP-1 receptor agonism promote human β-cell survival and improve glucose homeostasis in diabetic mice

Article

作者: Crowley, Liam A ; Cai, Renzhi ; Gonzalez Medina, Marel ; Wangpaichitr, Medhi ; Pita-Grisanti, Valentina ; Blandino-Rosano, Manuel ; Bernal-Mizrachi, Ernesto ; Louzada, Ruy A ; Sha, Wei ; Cui, Tengjiao

Abstract:

Type 1 diabetes (T1D) is characterized by progressive loss of pancreatic β cell mass driven by inflammatory cytokine–induced apoptosis. Although glucagon-like peptide-1 receptor (GLP-1R) agonists improve β cell function and survival, their efficacy may be limited under hyperglycemic conditions. Growth hormone–releasing hormone receptor (GHRH-R) agonists have emerged as potential β cell–protective agents through activation of cAMP-dependent signaling pathways. Here, we investigated the effects of the GHRH-R agonist MR-409, alone or in combination with the GLP-1R agonist exendin-4 (Ex-4), on β cell survival and glucose homeostasis. In human islets, combined MR-409 and Ex-4 treatment enhanced glucose-stimulated insulin secretion and increased CREB phosphorylation. The combination also reduced cytokine-induced apoptosis, with decreased caspase 3/7 activity compared with MR-409 alone and reduced BAX protein levels compared with either individual treatment. MR-409 alone increased IRS2 protein levels, consistent with activation of pro-survival signaling pathways. In a multiple low-dose streptozotocin (STZ) mouse model, MR-409, Ex-4, and their combination improved glucose homeostasis and increased β cell mass compared with vehicle-treated mice. However, the combination did not confer additional metabolic benefit over single treatments. Notably, MR-409 treatment was associated with greater improvements in glucose tolerance and insulin levels. These findings support further investigation of GHRH receptor agonism as a strategy to preserve β-cell survival under diabetogenic stress.

2026-09-01·NEUROPHARMACOLOGY

Broad glucagon-like peptide-1 (GLP-1) receptor distribution enhances glutamatergic transmission throughout the mouse cerebellar cortex

Article

作者: Rossi, David J ; Ritchey, Caitlin R ; Peters, James H ; Peterson, BreeAnne

The gut hormone glucagon-like peptide 1 (GLP-1) is a key contributor to the controls of food intake and reward processing. GLP-1 receptors (GLP-1R) are widely expressed throughout the central nervous system where their signaling alters neuronal excitability, resulting in suppressed food intake and reward. Recent studies have shown GLP-1R expression in Purkinje cells (PCs) within the cerebellum, a region gathering increasing appreciation for its role in sensory processing and appetitive behaviors. Importantly, the cerebellum responds to feeding signals and directly projects to key mesolimbic nuclei that initiate appetitive behaviors, including food intake. What remains unknown is if GLP-1Rs are expressed in other cell types of the cerebellum and the extent to which their activation produces neurophysiological changes. Here we combined RT-qPCR, RNAscope and immunohistochemistry with functional electrophysiology to map GLP-1R expression and signaling across the lobes and cell types of the cerebellar cortex of male/female C57BL/6N mice. We found that GLP-1Rs were nearly evenly expressed across all cerebellar lobes at the level of the vermis, as well as densely expressed in the deep cerebellar nuclei. At the cellular level, we found significant GLP-1R expression in granule cells (GCs) and GC-innervating mossy fibers, in addition to the previously reported expression in the PCs. Functionally, application of the GLP-1R agonist exendin-4 increased the frequency of spontaneous glutamate release on to the majority of recorded GCs and enhanced action potential firing in PCs. Together these results demonstrate broad expression of functional GLP-1R across cerebellar lobes which enhance synaptic transmission through the cerebellar cortex.

项与 GLP-1R Agonist (Biomea Fusion) 相关的新闻（医药）

2026-10-03

·微信

EASD 2026 | 减重与护肾"一箭双雕"：全球首创三靶点激动剂XTL6001亮相米兰，差异化突围GLP-1红海

导语：2026年9月28日至10月2日，第62届欧洲糖尿病研究协会（EASD）年会在意大利米兰举行。据麦科医药（2335.HK）披露，其自主研发的GLP-1R/GCGR/MasR三靶点长效蛋白药物XTL6001以两项口头报告的形式，公布了高质量减重与慢性肾病（CKD）/糖尿病肾病（DKD）两大方向的临床前及早期临床数据。在减重赛道从"卷减重幅度"转向"卷减重质量"的当下，这款将治疗维度从代谢调控延伸至器官保护的三靶点分子，为国产创新药的差异化突围提供了一个值得关注的样本。一、事件速览：一年三登国际顶级学术舞台本届EASD年会上，XTL6001的两项研究均以**口头报告（Oral Presentation）**形式呈现——在顶刊盛会上，口头报告的入选门槛显著高于壁报，通常意味着研究的新颖性与数据质量获得评审专家的更高认可： ·口头报告一：高质量减重方向——XTL6001与司美格鲁肽等摩尔剂量头对头的DIO小鼠系统研究（麦科医药CMO王湘玲博士主讲）； ·口头报告二：CKD/DKD肾脏保护方向——多种大、鼠模型中靶器官保护研究（麦科医药高级医学总监Lin主讲）。据公司公开信息，XTL6001年内已三次登上国际顶级学术平台：ADA 2026两项壁报 → EASD 2026两项口头报告 → ASN Kidney Week 2026壁报（高尿酸血症肾病方向）。一家Biotech的核心分子在糖尿病/代谢与肾脏病两大主流学界同时获得关注，本身即说明其差异化定位——不止于减重。二、机制解析：引入MasR，从"代谢改善"走向"器官保护" 目前主流减重代谢类药物多为GLP-1单靶点（如司美格鲁肽）或GLP-1/GIP双靶点（如替尔泊肽）设计，治疗重心集中在体重管控与代谢改善。而XTL6001选择了GLP-1R/GCGR基础上叠加MasR的三靶点路径，据公司披露为全球唯一进入临床阶段的GLP-1R/GCGR/MasR三重受体激动剂。 MasR是肾素-血管紧张素系统中ACE2/Ang-(1-7)/MasR保护性轴的功能性受体，具有抗炎、抗纤维化、促进肌蛋白合成、改善线粒体功能并诱导线粒体介导生热等多重作用，同时可扩张出球小动脉、降低肾小球内压、修复滤过屏障。三个靶点的分工可概括为： ·GLP-1R：抑制食欲、提升能量消耗，改善代谢与血流动力学； ·GCGR：促进脂肪分解与能量动员，同时保护肾小管免受脂质毒性损伤； ·MasR：锚定肾小球结构保护与抗纤维化，兼顾肌蛋白合成与肾脏保护。三者分别针对CKD/DKD病理级联中的代谢驱动、血流动力学异常、结构损伤和纤维化，理论上形成从上游到下游的全程覆盖——而非简单的药效叠加。三、数据解读：临床前与I期关键信息（一）高质量减重：DIO小鼠模型头对头司美格鲁肽据公司披露，在60%高脂饮食诱导肥胖（DIO）小鼠模型中，XTL6001与司美格鲁肽等摩尔剂量头对头比较，核心数据如下：指标 XTL6001 表现最大减重幅度 50.8%，在进食量高于司美格鲁肽的前提下，减重幅度提升约 33% 减重构成 "脂肪选择性减重"—— 脂肪量显著下降，肌肉量占比回升至正常水平停药后反弹体重回升速率仅为司美格鲁肽的约 1/2.3 内脏脂肪 130 nmol/kg 剂量下腹部脂肪减少 82.2%（司美格鲁肽为 51.1%）血脂 / 肝脂 LDL 降幅超 87.2%，肝脏甘油三酯下降 90.8%，ALT 恢复至正常范围其中最具差异化的信息点有二：一是"进食量不降反升的前提下减重更多"，提示其减重路径偏向提升能耗燃脂而非极端抑制食欲，即"减脂不减肌"的高质量减重；二是停药反弹更慢——体重维持是当前GLP-1类药物临床管理中的公认痛点。（二）I期临床：安全性良好，代谢获益初现 XTL6001中国I期研究已完成，仅4-5周用药即显示：整体安全性良好，支持每周一次皮下给药；体重下降、腰围明显缩小，且停药2周内仍见腰围持续缩小；尿酸、血脂全面改善，高BMI人群甘油三酯降幅超40%。需要客观指出的是，I期样本量与观察周期有限，上述获益仍属"初步信号"，确证性疗效有待后续II/III期临床验证。（三）肾脏保护：三种模型中白蛋白尿降幅最高约88% 据公司披露，XTL6001在多种CKD/DKD动物模型中展示了靶器官保护数据，对照组涵盖非奈利酮、度拉糖肽、苯溴马隆及别嘌醇：模型关键结果重度 DKD 大鼠（STZ + 单侧肾切除） 0.5 mg/kg 使 UACR 降低 62.9%，约为 "非奈利酮 + 度拉糖肽" 联合组降幅（10.9%）的 6 倍；24 小时尿白蛋白、血尿酸、血肌酐分别降低 54.7%、28.8%、21.3% DKD 大鼠（四氧嘧啶 + 单侧肾切除）部分组 UACR 降幅约为非奈利酮的 3 倍，血尿酸降至接近假手术组水平 CKD + 高尿酸血症小鼠（腺嘌呤 + 氧嗪酸钾）尿白蛋白降低 80.2%，多个终点优于苯溴马隆综合三种模型，白蛋白尿较溶媒对照组降幅最高约88%。机制上，XTL6001通过MasR直接改善肾血流与尿酸排泄，借助GLP-1R/GCGR减轻尿酸生成的代谢驱动因素，形成"代谢-肾脏"双通道降尿酸机制。公司亦同步布局蛋白尿性CKD与MASH适应症。四、赛道观察：红海之中，"减重+"的差异化分支正在形成 IQVIA估计，2024-2034年全球减重药物市场将以13%-15%的复合年增长率增长，规模预计达约1300亿美元。但与此同时，国内赛道已进入"诸神混战"：司美格鲁肽、替尔泊肽占据先发优势并发起降价潮，玛仕度肽（GLP-1R/GCGR双靶点）作为国产首款双靶点减重药快速放量，埃诺格鲁肽、恒瑞HRS9531、翰森奥莱泊肽等相继获批或申报上市。当"减重幅度"的边际提升越来越难构成壁垒，行业竞争焦点正转向安全性、减重质量与适应症边界三个方向。 XTL6001的定位恰好踩中其中两条：高质量减重（保留肌肉、停药反弹慢）与适应症外延（CKD/DKD、MASH、高尿酸血症）。代表药物靶点研发方阶段差异点司美格鲁肽 GLP-1R 诺和诺德已上市单靶点 "金标准" 替尔泊肽 GLP-1R/GIPR 礼来已上市双靶点，减重幅度领先玛仕度肽 GLP-1R/GCG R 信达生物中国已上市 GCG 靶点契合腹型肥胖 XTL6001 GLP-1R/GCG R/MasR 麦科医药 I 期完成（中美双 IND）三靶点：减重 + 肌保护 + 肾脏保护值得注意的是，肥胖是CKD的独立危险因素——肥胖人群CKD发病风险提升46%、蛋白尿风险提升55%，重度肥胖人群肾衰竭风险达正常人群的3.46倍；全球CKD患者约7.88亿，中国患者达1.52亿居全球之首。在"肥胖-代谢-肾脏"这条疾病链上，用单一分子同时干预多个环节，是XTL6001与现有GLP-1类药物最本质的区别。参考资料（部分）： 1. 麦科医药（2335.HK）官方公众号及港交所自愿性公告（2026年8月17日）：XTL6001研究获接纳于EASD 2026及ASN Kidney Week 2026作报告 2. 《柳叶刀》全球疾病负担2023研究（CKD流行病学数据） 3. IQVIA：2024-2034年全球减重药物市场预测 4. 第六次中国慢性病监测数据及相关临床研究（肥胖与CKD风险数据）药渡媒体商务合作媒体公关 | 新闻&会议发稿张经理：18600036371（微信同号）点击下方“药渡”，关注更多精彩内容免责声明本文基于公开信息整理撰写，其中涉及XTL6001的临床前研究数据均引自麦科医药官方披露，尚未经同行评审发表，不代表监管审批结论；临床前数据不等同于临床疗效。本文仅作行业信息交流，不构成任何投资建议或用药建议，亦不构成对任何药物的推广。

申请上市

2026-10-03

·麦科奥特

EASD 2026米兰| 麦科医药XTL6001两项研究作口头报告，全球首创三靶点激动剂获高度关注

MICOT 点击蓝字关注我们 Slide to view different languages 滑动查看不同语言 2026年第62届欧洲糖尿病研究协会（EASD）年会于9月28日至10月2日在意大利米兰隆重举行。麦科医药（2335.HK）自主研发的全球首创GLP-1R/GCGR/MasR三靶点长效蛋白在研药物XTL6001，在高质量减重与慢性肾病（CKD）/糖尿病肾病（DKD）两大领域的研究成果，通过口头报告（Oral Presentation）亮相国际顶级学术舞台，成为本届大会备受关注的中国创新研究之一，彰显了中国原研创新药在代谢与肾脏疾病领域的研发实力与国际影响力。全球首创三靶点长效蛋白：从高质量减重到肾脏保护 XTL6001是麦科医药自主研发的全球唯一一款进入临床阶段的GLP-1R/GCGR/MasR三重受体激动剂。与传统GLP-1单靶点或GLP-1/GIP双靶点药物不同，XTL6001在GLP-1R和GCGR的控制食欲、提升能量消耗、促进脂肪分解的基础上，创新性地引入了具有抗炎、抗纤维化、促进肌蛋白合成、改善线粒体功能并诱导线粒体介导生热的MasR靶点，同时具备肾脏保护的多个机制和作用。三靶点各司其职又互为协同，全面提升代谢获益及器官保护。临床前动物试验（高质量减重）：提供高质量减重，燃脂并保留肌肉与水分麦科医药首席医学官（CMO）王湘玲博士在口头报告中，介绍了XTL6001在60%高脂饮食诱导肥胖（DIO）小鼠模型中、与司美格鲁肽等摩尔剂量头对比较的系统研究。结果显示： 01 最大减重幅度达50.8%，在相同剂量下XTL6001在整体进食量超过司美格鲁肽的前提下，实现减重幅度提升约33%，提示XTL6001的减重方案是燃脂而强力抑制食欲； 02 呈现明确的"脂肪选择性减重"及良好保留肌肉与水的特征——减掉的重量主要来自于脂肪量的显著下降，同时肌肉量占比升至正常水平，实现充分减脂并保留肌肉的高质量减重； 03 停药后体重维持更优，XTL6001的体重回升速率低于司美格鲁肽2.3倍，提示反弹更小； 04 在130 nmol/kg等摩尔剂量下，XTL6001使腹部脂肪减少82.2%，降幅为司美格鲁肽（-51.1%）的1.61倍，更强力清除内脏脂肪； 05 血脂、肝脂同步改善：LDL（低密度脂蛋白胆固醇）降幅超过87.2%，肝脏甘油三酯下降90.8%，近乎完全逆转肝脏脂肪变性，ALT（丙氨酸氨基转移酶）等指标恢复至正常范围，展现治疗MASH（代谢功能障碍相关脂肪性肝炎）的潜力；临床Ⅰ期研究：安全性良好，代谢获益初步显现在已经完成的仅用药4-5周临床I期结果显示，XTL6001整体安全性良好，支持每周一次给药，临床前的获益在1期也有部分展现：体重下降、腰围明显缩小且停药后2周内仍见持续的腰围缩小、尿酸、血脂的全面改善，尤其是甘油三酯在高BMI人群中下降超过40%。 CMO王湘玲 “XTL6001最核心的差异化，在于通过GLP-1R、GCGR与MasR三靶点协同，实现了强效减重与极端食欲抑制的解耦——它通过提升能耗‘燃烧脂肪’，而不是简单让身体挨饿。同时阻断骨骼肌蛋白质降解、促进肌蛋白合成、防止肌肉流失，从机制层面破解了传统减重药物‘减脂必减肌’的困境，及常见的肌少型肥胖治疗难题，这种高质量的减重，配合对血糖、血脂、尿酸的全面代谢改善，正是我们希望带给肥胖及代谢疾病患者的新选择。现场专家围绕脂肪选择性减重与停药后体重维持的机制给予了积极评价，这也让我们对中国原研创新药走向国际舞台更加有信心。” 临床前动物试验（肾脏保护）：多种CKD/DKD模型中白蛋白尿降幅最高约88% 麦科医药高级医学总监Lin在口头报告中，展示了XTL6001在多种大鼠及小鼠慢性肾病/糖尿病肾病模型中的靶器官保护数据，对照涵盖非奈利酮、度拉糖肽、苯溴马隆及别嘌醇。XTL6001核心差异化在于引入MasR靶点——肾素-血管紧张素系统中ACE2/Ang-(1-7)/MasR保护性轴的功能性受体，可扩张出球小动脉、降低肾小球内压、修复滤过屏障并拮抗纤维化，将治疗从代谢领域延伸至肾脏保护。三靶点协同机制可概括为：GLP-1R主要改善代谢与血流动力学，GCGR保护肾小管免受脂质毒性损伤，MasR锚定肾小球结构保护与抗纤维化。三者分别针对CKD/DKD病理级联中的代谢驱动、血流动力学异常、结构损伤和纤维化，形成从上游到下游的全程覆盖，而非简单叠加。临床前数据充分验证了协同优势：伴蛋白尿的重度DKD大鼠模型（STZ+单侧肾切除）：0.5 mg/kg使UACR较溶媒对照组降低62.9%，约为“非奈利酮+度拉糖肽”组降幅（-10.9%）的6倍；24小时尿白蛋白、血尿酸和血清肌酐也分别较溶媒对照组降低54.7%、28.8%和21.3%，HbA1c同步下降。XTL6001单分子即实现了约6倍于“MRA+GLP-1RA”联合逻辑的降蛋白尿效力。另一DKD大鼠模型（四氧嘧啶+单侧肾切除）：部分组UACR较溶媒对照组的降幅约为非奈利酮组的3倍，血尿酸降至接近假手术组水平。小鼠CKD+蛋白尿+高尿酸血症模型（腺嘌呤+氧嗪酸钾）：剂量依赖性降低尿白蛋白、UACR、血肌酐与血尿酸，尿白蛋白较溶媒对照组降幅达80.2%，多个终点优于苯溴马隆。综合三种模型，白蛋白尿较溶媒对照组降幅最高约88%，同时维持肾功能、降低血尿酸并改善代谢指标。XTL6001通过MasR直接改善肾血流和尿酸排泄，并借助GLP-1R/GCGR减轻尿酸生成驱动因素，形成“代谢-肾脏”双通道降尿酸机制。高级医学总监 Lin “肾损伤机制复杂，主流单靶点或多药联合也难以全面覆盖，残余风险仍存在。XTL6001在GLP-1R和GCGR基础上引入MasR，将治疗从‘代谢改善’拓展至‘肾脏结构保护’，形成真正意义上的‘减重-代谢-肾脏’三靶点协同干预，有望为CKD/DKD患者提供同时靶向蛋白尿、肾功能不全及高尿酸血症的多维度治疗解决方案。” 关于XTL6001 XTL6001是麦科医药自主研发的全球首创GLP-1R/GCGR/MasR三靶点长效蛋白药物，为Fc融合蛋白长效分子，皮下注射、每周一次给药。其独特之处在于，将药物治疗维度从减重、代谢调控拓展至多器官保护。XTL6001已在中美两国获批开展临床试验，并在中国顺利完成I期临床。继ADA 2026两项壁报、EASD 2026两项口头报告之后，XTL6001肾脏病研究又入选ASN Kidney Week 2026壁报展示，一年内三次进入国际顶级学术交流平台。 MICOT The 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) was held in Milan, Italy, from Sep 28 to Oct 2, 2026. Findings on XTL6001, a first-in-class, long-acting GLP-1R/GCGR/MasR triple-agonist protein therapeutic developed in-house by Micot Pharma (2335.HK), in the two fields of high-quality weight loss and chronic kidney disease (CKD)/diabetic kidney disease (DKD) were shared in oral presentations at this premier global scientific forum. The research was among the Chinese innovations that drew strong interest at this year’s meeting, highlighting China’s R&D strength and the global influence of its independently developed innovative drugs in metabolic and kidney diseases. A First-in-Class, Long-Acting Triple-Agonist Protein Therapeutic: From High-Quality Weight Loss to Kidney Protection XTL6001, developed in-house by Micot Pharma, is the world’s only clinical-stage GLP-1R/GCGR/MasR triple agonist. Unlike conventional single-target GLP-1 or dual-target GLP-1/GIP drugs, XTL6001 builds on GLP-1R and GCGR’s roles in controlling appetite, increasing energy expenditure, and promoting lipolysis by introducing MasR as an innovative target that has anti-inflammatory and antifibrotic effects, promotes muscle protein synthesis, improves mitochondrial function, and induces mitochondria-mediated thermogenesis, while also providing kidney protection through multiple mechanisms and actions. Each of the three targets has a distinct role and synergizes with the others to comprehensively enhance metabolic benefits and organ protection. Preclinical Animal Studies (High-Quality Weight Loss): Delivering High-Quality Weight Loss by Burning Fat While Preserving Muscle and Body Water In her oral presentation, Dr. Xiangling Wang, Micot Pharma’s Chief Medical Officer (CMO), presented a systematic study comparing XTL6001 head-to-head with semaglutide at equimolar doses in a 60% high-fat diet-induced obesity (DIO) mouse model. The results showed: 01 Maximum weight loss reached 50.8%. At the same dose, XTL6001 achieved about 33% greater weight loss despite higher total food intake than with semaglutide, suggesting that XTL6001’s weight-loss approach involves fat burning rather than strong appetite suppression; 02 XTL6001 showed clear “fat-selective weight loss,” with good muscle and body water preservation—the weight lost was mainly due to a marked fat mass reduction, while muscle’s share of body weight rose to normal levels, achieving high-quality weight loss through substantial fat loss while preserving muscle; 03 Weight loss was better maintained after treatment cessation. Semaglutide’s weight regain rate was 2.3 times XTL6001’s, suggesting less rebound weight gain with XTL6001; 04 At an equimolar dose of 130 nmol/kg, XTL6001 reduced abdominal fat by 82.2%, a reduction 1.61 times that with semaglutide (−51.1%), achieving greater visceral fat reduction; 05 Blood and liver lipids improved concurrently: LDL cholesterol fell by >87.2%, and hepatic triglycerides fell by 90.8%, almost completely reversing hepatic steatosis. ALT (alanine aminotransferase) and other parameters normalized, showing potential to treat MASH (metabolic dysfunction-associated steatohepatitis). Phase I Clinical Study: Favorable Safety Profile and Early Evidence of Metabolic Benefits Results from the completed Phase I clinical study, which involved only 4–5 weeks of treatment, showed that XTL6001 had a favorable overall safety profile and supported once-weekly dosing. Some preclinical benefits were also seen in Phase I: weight loss; a marked waist circumference reduction, with continued reductions still seen within 2 weeks after treatment cessation; and comprehensive uric acid and blood lipid improvements, with triglycerides particularly falling by >40% in high-BMI participants. CMO “XTL6001’s key differentiator is that, through synergy among GLP-1R, GCGR, and MasR, it decouples potent weight loss from extreme appetite suppression—it ‘burns fat’ by increasing energy expenditure rather than simply starving the body. Simultaneously, it blocks skeletal muscle protein breakdown, promotes muscle protein synthesis, and prevents muscle loss, overcoming, at the mechanistic level, the dilemma with conventional weight-loss drugs that ‘fat loss necessarily means muscle loss,’ and the common challenges in treating sarcopenic obesity. This high-quality weight loss, with comprehensive metabolic improvements in blood glucose, blood lipids, and uric acid, is exactly the new option we hope to offer patients with obesity and metabolic diseases. Experts at the meeting commented positively on the mechanisms underlying fat-selective weight loss and weight-loss maintenance after treatment cessation, further strengthening our confidence in bringing innovative drugs developed in China to the global stage.” Preclinical Animal Studies (Kidney Protection): Reductions in Albuminuria of Up to About 88% Across Multiple CKD/DKD Models In the oral presentation, Micot Pharma’s Senior Medical Director, Lin, presented data on target-organ protection with XTL6001 in multiple rat and mouse CKD/DKD models, with comparators including finerenone, dulaglutide, benzbromarone, and allopurinol. A key XTL6001 differentiator is the addition of MasR—the functional receptor in the protective ACE2/Ang-(1-7)/MasR axis of the renin–angiotensin system—which can dilate efferent arterioles, reduce intraglomerular pressure, repair the filtration barrier, and counteract fibrosis, extending treatment from the metabolic field to kidney protection. The three targets’ synergistic mechanisms can be summarized as follows: GLP-1R primarily improves metabolism and hemodynamics; GCGR protects renal tubules from lipotoxic injury; and MasR mediates glomerular structural protection and antifibrotic effects. Together, the three targets address metabolic drivers, hemodynamic abnormalities, structural injury, and fibrosis in CKD/DKD’s pathological cascade, providing full coverage from upstream to downstream rather than mere additivity. The preclinical data robustly validate these synergistic advantages: In a severe DKD rat model with proteinuria (STZ + unilateral nephrectomy), 0.5 mg/kg reduced the urinary albumin-to-creatinine ratio (UACR) by 62.9% vs. vehicle control, about 6 times the reduction in the “finerenone + dulaglutide” group (−10.9%). Compared with vehicle control, 24-hour urinary albumin, blood uric acid, and serum creatinine also fell by 54.7%, 28.8%, and 21.3%, respectively, with a concurrent HbA1c reduction. As a single molecule, XTL6001 achieved an antiproteinuric effect about 6 times that of the “MRA + GLP-1RA” combination. In another DKD rat model (alloxan + unilateral nephrectomy), the UACR reduction vs. vehicle control in some treatment groups was about 3 times that with finerenone, while blood uric acid fell to near the sham-operated group’s level. In a CKD mouse model with proteinuria and hyperuricemia (adenine + potassium oxonate), XTL6001 dose-dependently reduced urinary albumin, UACR, blood creatinine, and blood uric acid. Urinary albumin fell by 80.2% vs. vehicle control, with outcomes superior to those with benzbromarone across multiple endpoints. Across the three models, albuminuria fell by up to about 88% vs. vehicle control, while kidney function was maintained, blood uric acid was reduced, and metabolic parameters improved. XTL6001 directly improves renal blood flow and uric acid excretion through MasR and, through GLP-1R/GCGR, reduces the factors driving uric acid production, establishing a dual-pathway metabolic–renal uric acid-lowering mechanism. Senior MedicalDirector “Kidney injury mechanisms are complex, and even mainstream single-target therapies or multidrug combinations cannot readily provide full coverage, leaving residual risk. By adding MasR to GLP-1R and GCGR, XTL6001 extends treatment from ‘metabolic improvement’ to ‘kidney structural protection,’ creating a truly synergistic triple-target intervention spanning ‘weight loss, metabolism, and kidney protection.’ This approach has the potential to provide patients with CKD/DKD with a multidimensional therapeutic solution that simultaneously targets proteinuria, renal insufficiency, and hyperuricemia.” About XTL6001 XTL6001 is a first-in-class, long-acting GLP-1R/GCGR/MasR triple-agonist protein therapeutic developed in-house by Micot Pharma. It is a long-acting Fc fusion protein administered once weekly subcutaneously. Its distinctive feature is that it extends pharmacotherapy from weight loss and metabolic regulation to multi-organ protection. XTL6001 has received regulatory clearance for clinical studies in both China and the US and has successfully completed its Phase I clinical study in China. Following two posters at ADA 2026 and two oral presentations at EASD 2026, XTL6001 kidney disease research has also been accepted for poster presentation at ASN Kidney Week 2026, marking its inclusion in three premier global scientific forums within one year. MICOT

2026-07-23

·PRNewswire

Ascletis Announces Oral Discussion of ASC36_35 FDC Preclinical Data Demonstrating Superior Weight Loss to Eloralintide/Tirzepatide Combination at the 62nd European Association for the Study of Diabetes (EASD) Annual Meeting

- Fixed-dose combination of ASC36 and ASC35 (ASC36_35 FDC) demonstrated superior weight loss compared to eloralintide in combination with tirzepatide in a diet-induced obese (DIO) animal model. HONG KONG, July 22, 2026 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX: 1672, "Ascletis") announces that preclinical data of ASC36_35 FDC, a once-monthly injection co-formulation of ASC36, a peptide amylin receptor agonist, and ASC35, a peptide GLP-1R/GIPR agonist, for the treatment of obesity, will be presented in a short oral discussion at the 62nd European Association for the Study of Diabetes (EASD) Annual Meeting being held in Milan, Italy. The data demonstrate superior weight loss to the eloralintide in combination with tirzepatide in a diet-induced obese (DIO) animal model. Details of the Short Oral Discussion Abstract Title: Co-formulation of ASC36 and ASC35, once-monthly amylin receptor agonist and GLP-1R/GIPR agonist, demonstrated superior weight loss to eloralintide/tirzepatide combo in DIO rats Short Oral Discussion Event F Short Oral Discussion Session: SO 066 Emerging agents: amylin, oral molecules and beyond Short Oral Discussion Station 11 Presentation Time: Thursday, October 1, 2026, 14:00 - 15:00 CEST Presentation Number: 768 "We believe the co-formulation of ASC36 and ASC35 has the potential to lead to greater weight loss in people with obesity than eloralintide/tirzepatide combination can achieve, based on these preclinical data," said Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis, "The selection of these data for oral discussion at EASD 2026 reflects the importance of advancing new treatment options for patients with obesity." About ASC36_35 FDC ASC36_35 FDC, a once-monthly subcutaneous (SQ) injection co-formulation of ASC36 and ASC35, is a potentially first-in-class drug candidate targeting three validated targets of amylin receptor, GLP-1R and GIPR. ASC36_35 FDC once-monthly co-formulation is Self-Assembling Lipid Depot (SALD) formulation, developed in-house utilizing Ascletis' Ultra-Long-Acting Platform (ULAP) technology. About the European Association for the Study of Diabetes (EASD) Founded in 1965 and based in Düsseldorf, Germany, the European Association for the Study of Diabetes (EASD) aims to encourage and support research in the field of diabetes, the rapid diffusion of acquired knowledge and to facilitate its application. The EASD Annual Meeting features groundbreaking basic research, cutting-edge clinical trial results and in-depth expert debates. The 62nd EASD Annual Meeting will be held in Milan, Italy, from September 28 to October 2, 2026. About Ascletis Pharma Inc. Ascletis Pharma Inc. is a fully integrated biotechnology company focused on the development and commercialization of potentially best-in-class and first-in-class therapeutics to treat metabolic diseases. Utilizing its proprietary Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD) and Ultra-Long-Acting Platform (ULAP) technologies as well as Peptide Oral Transport ENhancement Technology (POTENT), Ascletis has developed multiple drug candidates in-house, including both small molecules and peptides, such as its lead program, ASC30, a small molecule GLP-1R agonist designed to be administered once daily orally and once monthly to once quarterly subcutaneously as a treatment therapy and a maintenance therapy for chronic weight management; ASC36, an amylin receptor peptide agonist, ASC35, a once-monthly subcutaneously administered GLP-1R/GIPR dual peptide agonist and ASC37, a GLP-1R/GIPR/GCGR triple peptide agonist, ASC39, an eloralintide-like potent and amylin-selective oral small molecule amylin receptor agonist, ASC30_39 FDC, a fixed-dose combination (FDC) of ASC30 (GLP-1 RA) and ASC39 (amylin RA), ASC30_48 FDC, a fixed-dose combination (FDC) of ASC30 (GLP-1 RA) and ASC48 (GIP RA), for chronic weight management. Ascletis is listed on the Hong Kong Stock Exchange (1672.HK). For more information, please visit . Contact: Peter Vozzo ICR Healthcare 443-231-0505 (U.S.) [email protected] Ascletis Pharma Inc. PR and IR Teams +86-181-0650-9129 (China) [email protected] [email protected] SOURCE Ascletis Pharma Inc. 21% more press release views with Request a Demo

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