XTL6001

MICOT 点击蓝字 关注我们 Slide to view different languages  滑动查看不同语言 10月21日至25日，2026年美国肾脏病学会肾脏周（ASN Kidney Week 2026）在美国丹佛举行。作为全球规模最大、最具权威性的肾脏病学年度学术盛会，本届大会汇聚了全球超万名专业人士。 麦科医药（02335.HK）自主研发的全球首创（First-in-Class）MasR/GLP-1R/GCGR三靶点激动剂XTL6001成功入选大会壁报展示。这是继ADA 2026两项壁报、EASD 2026两项壁报之后，XTL6001年内第三次登上国际顶级学术舞台，标志着其独特的“多靶点协同”机制获得了国际代谢及肾脏病学界的持续高度认可，也开启了从代谢领域向肾脏保护的加速跨越，覆盖更广阔的临床领域。 直面临床痛点： 高尿酸合并慢性肾脏病亟待“多效合一”的破局者 慢性肾脏病（CKD）是全球性的重大公共卫生挑战。据《柳叶刀》发表的全球疾病负担研究数据，全球成人慢性肾脏病患病率已达14.2%，患者总数高达7.88亿[1]。观察性研究显示高尿酸血症与CKD的快速进展密切相关，合并高尿酸血症的CKD患者需要同时进行尿酸控制与肾脏保护，这代表着一个关键且尚未被满足的临床需求[2]。 然而，现有治疗手段难以覆盖这一诉求：蛋白尿、肾小球滤过功能丧失与代谢功能障碍三者相互促进，形成复杂的恶性闭环，而单靶点药物往往只能覆盖闭环中的一环。[3]如何在同一款药物上实现“降尿酸”与“护肾脏”的协同，成为肾脏病与代谢领域共同关注的命题。 单药“三合一”：一条分子链上补齐三个关键环节 XTL6001是麦科医药自主研发的全球首创（First-in-Class）MasR/GLP-1R/GCGR三重受体激动剂，为重组人三靶点激动肽Fc融合蛋白。它并未止步于主流药物惯用的GLP-1通路，而是创新性地引入了具有抗炎、抗纤维化及肾脏保护意义的MasR通路[4]——三条通路各司其职、协同作战： MasR通路（核心差异点）：作为Ang-(1-7)的受体，MasR可介导保护性的ACE2/Ang-(1-7)/MasR轴，拮抗过度激活的ACE/Ang II/AT1R轴，直接降低肾小球内压，发挥抗炎、抗纤维化作用，并保护肾小球滤过屏障[4]。 GCGR 通路：调节肾脏尿酸转运、增强尿酸排泄，同时抑制肝脏嘌呤代谢，从 "生成" 与 "排出" 两端共同降低尿酸负荷 [5、6]。 GLP-1R 通路：改善胰岛素敏感性、减轻体重，从源头优化影响肾脏的全身代谢环境；同时发挥抗炎、抗纤维化作用，并通过利钠驱动增强尿酸排泄 [7]。 三条通路的组合，使 XTL6001 得以在单一分子上全面拦截 CKD / 糖尿病肾病（DKD）的致病级联反应 ——从代谢紊乱、肾实质损伤到肾功能恶化，形成 "代谢改善（含降尿酸）＋降低尿蛋白＋肾功能保护" 的多维治疗矩阵；壁报数据支持其对 "血尿酸— 尿蛋白 — 肾功能保护" 全链条的干预。 壁报核心数据：临床前与首次人体双重验证 本次ASN壁报（TH-PO0252）系统展示了XTL6001在肾脏保护领域的核心临床前及临床数据： 临床前研究：多维度肾脏保护证据一致 在三种不同的经典肾脏疾病动物模型中，XTL6001均展现出一致的肾脏保护效应——剂量依赖性降低蛋白尿、改善高滤过状态、保护肾功能并显著降低肾脏指数。它首次以单一分子药物，从改善全身代谢紊乱、减轻肾脏血流动力学异常，到延缓肾功能衰退，逐一掐断了慢性肾脏病这条相互强化的恶性闭环。 首次人体临床：降尿酸信号明确，安全性良好 在健康成人中开展的随机、双盲、安慰剂对照 I 期研究（NCT07205432）显示： 01 强效持久降尿酸：每周给药至第22天，血清尿酸较基线下降约 20%；停药5周后，仍较基线低约 11%。 02 促进尿酸排泄：D22 时 XTL6001 组尿酸清除率较基线升高 +12%，而安慰剂组下降 −28%—— 相对安慰剂的差值为 +40%。 03 药代动力学特征可预测：Tmax 12–36 h，t½ 约 24–29 h，单次与多次给药后半衰期一致，无蓄积；BMI 越高降尿酸效应越显著。 04 安全性良好：未报告严重不良事件（SAEs）；多数 AE 为 1–2 级，胃肠道 AE 呈剂量依赖性且可控，局部耐受性良好；未检测到治疗期抗药抗体（ADA），免疫原性风险低，为后续长期给药奠定了坚实基础。 综合临床前与首次人体数据，XTL6001作为全球首创的MasR/GCGR/GLP-1R三靶点激动剂，在代谢调控之外兼具直接的肾脏保护作用，有望以单药形式填补高尿酸血症合并慢性肾脏病人群“既需控尿酸、又需护肾脏”的治疗空白。麦科医药将持续推进XTL6001的临床开发，期待这款源自中国的创新药早日为全球慢性肾脏病及代谢性疾病患者带来全新的治疗选择。 重要提示 XTL6001尚处于临床试验阶段，未获批上市；本文所引数据来自早期探索性研究，不等同于最终临床结论，不构成任何用药推荐。所有治疗决策请遵从专科医生指导。 参考文献 [1]  GBD 2023 Chronic Kidney Disease Collaborators. Global, regional, and national burden of chronic kidney disease in adults, 1990-2023, and its attributable risk factors: a systematic analysis for the Global Burden of Disease Study 2023. The Lancet. 2025;406(10518):2461-2482. [2]  Li L, et al. BMC Nephrol. 2014;15:122. [3]  Astor BC, Matsushita K, Gansevoort RT, et al. Kidney Int. 2011;79(12):1331-1340. [4]  Silveira KD, et al. PLoS One. 2013;8(6):e66082. [5]  Yamamoto T, et al. J Rheumatol. 1997;24(4):708-713. [6]  Ren Y, et al. Mazdutide, a dual GLP-1R/GCGR agonist, inhibits hepatic purine metabolism. Diabetes. 2025;74(Suppl 1):775-P. [7]  Najafi S, et al. Br J Clin Pharmacol. 2022;88(8):3627-3637. MICOT ASN Kidney Week 2026, the annual meeting of the American Society of Nephrology, was held in Denver, Colorado, USA, from October 21 to 25. As the world's largest and most authoritative annual scientific meeting in nephrology, this year's meeting brought together more than 10,000 professionals from around the world. XTL6001, a first-in-class MasR/GLP-1R/GCGR triple agonist independently developed by Micot (02335.HK), was selected for poster presentation at the meeting. Following two poster presentations at ADA 2026 and two at EASD 2026, this marks the third time this year that XTL6001 has been featured at a leading international scientific congress. It reflects the sustained recognition of its distinctive "multitarget synergy" mechanism by the international metabolic and nephrology communities, and signals an accelerated extension of its development from metabolic disease into renoprotection, encompassing a broader range of clinical indications. Confronting an Unmet Clinical Need: Hyperuricemia with Chronic Kidney Disease Calls for a "Multiple Benefits in One" Solution Chronic kidney disease (CKD) is a major global public health challenge. According to the Global Burden of Disease Study published in The Lancet, the global prevalence of CKD among adults has reached 14.2%, affecting a total of 788 million individuals.[1] Observational studies have shown that hyperuricemia is closely associated with rapid progression of CKD; patients with CKD and concomitant hyperuricemia require both urate control and renoprotection, representing a critical unmet clinical need.[2] However, existing therapies fall short of meeting this need. Proteinuria, loss of glomerular filtration function and metabolic dysfunction reinforce one another, forming a complex vicious cycle, and single-target agents typically address only one component of this cycle.[3] How to achieve synergistic urate lowering and renoprotection with a single agent has therefore become a shared question in nephrology and metabolic medicine. A Three-in-One Single Agent: Addressing Three Key Pathways with One Molecule XTL6001, independently developed by Micot, is a first-in-class MasR/GLP-1R/GCGR triple receptor agonist—a recombinant human triple-agonist peptide Fc fusion protein. Rather than relying solely on the GLP-1 pathway used by mainstream agents, it innovatively incorporates the MasR pathway, which has anti-inflammatory, antifibrotic and renoprotective relevance.[4] The three pathways play distinct and complementary roles: • MasR pathway (key differentiator): As the receptor for angiotensin-(1–7) [Ang-(1–7)], MasR mediates the protective ACE2/Ang-(1–7)/MasR axis, counteracting the overactivated ACE/Ang II/AT1R axis. It directly lowers intraglomerular pressure, exerts anti-inflammatory and antifibrotic effects, and protects the glomerular filtration barrier.[4] • GCGR pathway: Modulates renal urate transport and enhances urate excretion while inhibiting hepatic purine metabolism, thereby reducing the urate burden at both the "production" and "excretion" ends.[5,6] • GLP-1R pathway: Improves insulin sensitivity and reduces body weight, optimizing at its source the systemic metabolic milieu that affects the kidney; it also exerts anti-inflammatory and antifibrotic effects and enhances urate excretion through natriuresis.[7] By combining these three pathways, XTL6001 is able to comprehensively intercept the pathogenic cascade of CKD/diabetic kidney disease (DKD) with a single molecule—from metabolic derangement and renal parenchymal injury through to deterioration of renal function—forming a multidimensional "metabolic improvement (including urate lowering) + proteinuria reduction + renal function preservation" therapeutic profile. The poster data support intervention across the entire "serum uric acid–proteinuria–renal function preservation" continuum. Key Poster Data: Dual Validation in Preclinical and First-in-Human Studies The ASN poster (TH-PO0252) presented the key preclinical and clinical data for XTL6001 in renoprotection: Preclinical studies: consistent evidence of multidimensional renoprotection Across three established animal models of kidney disease, XTL6001 demonstrated consistent renoprotective effects: dose-dependent reduction of proteinuria, amelioration of glomerular hyperfiltration, preservation of renal function and significant reduction of the kidney index. As a single-molecule agent, it was the first to sequentially interrupt each link of the self-reinforcing vicious cycle of CKD—from correcting systemic metabolic derangement and attenuating abnormal renal hemodynamics to slowing the decline in renal function. First-in-human study: clear urate-lowering signal and favorable safety A randomized, double-blind, placebo-controlled Phase I study in healthy adults (NCT07205432) showed the following: 01 Potent and sustained urate lowering: With once-weekly dosing, serum uric acid decreased by approximately 20% from baseline by Day 22, and remained approximately 11% below baseline 5 weeks after the last dose. 02 Enhanced urate excretion: On Day 22, uric acid clearance increased by 12% from baseline in the XTL6001 group, compared with a 28% decrease in the placebo group—a placebo-adjusted difference of +40 percentage points. 03 Predictable pharmacokinetics: Tmax was 12–36 h and t½ was approximately 24–29 h; the half-life was consistent after single and multiple doses, with no accumulation. The urate-lowering effect was more pronounced in participants with higher body mass index (BMI). 04 Favorable safety profile: No serious adverse events (SAEs) were reported. Most adverse events (AEs) were Grade 1–2; gastrointestinal AEs were dose-dependent and manageable, and local tolerability was good. No treatment-emergent anti-drug antibodies (ADAs) were detected, indicating a low risk of immunogenicity and providing a solid foundation for long-term dosing. Taken together, the preclinical and first-in-human data indicate that XTL6001, a first-in-class MasR/GCGR/GLP-1R triple agonist, provides direct renoprotective effects in addition to metabolic regulation, and has the potential, as a single agent, to fill the therapeutic gap for patients with hyperuricemia and CKD who require both urate control and renoprotection. Micot will continue to advance the clinical development of XTL6001, with the aim of bringing this innovative drug originating in China to patients with CKD and metabolic diseases worldwide as a new treatment option. Important Notice XTL6001 is currently in clinical development and has not been approved for marketing. The data cited in this article are derived from early exploratory studies, do not constitute final clinical conclusions, and do not constitute any recommendation for medication use. All treatment decisions should follow the guidance of a specialist physician. References [1] GBD 2023 Chronic Kidney Disease Collaborators. Global, regional, and national burden of chronic kidney disease in adults, 1990–2023, and its attributable risk factors: a systematic analysis for the Global Burden of Disease Study 2023. Lancet. 2025;406(10518):2461-2482. [2] Li L, et al. BMC Nephrol. 2014;15:122. [3] Astor BC, Matsushita K, Gansevoort RT, et al. Kidney Int. 2011;79(12):1331-1340. [4] Silveira KD, et al. PLoS One. 2013;8(6):e66082. [5] Yamamoto T, et al. J Rheumatol. 1997;24(4):708-713. [6] Ren Y, et al. Mazdutide, a dual GLP-1R/GCGR agonist, inhibits hepatic purine metabolism. Diabetes. 2025;74(Suppl 1):775-P. [7] Najafi S, et al. Br J Clin Pharmacol. 2022;88(8):3627-3637. MICOT

10月15日，麦科医药-B（02335.HK）发布公告，董事会建议采纳H股激励计划，有效期为自采纳日期起计十年，并将于临时股东会上寻求股东批准。同时，董事会寻求授出不超过已发行H股总数10%的股份回购一般授权。根据公告，H股激励计划旨在为公司提供吸引、激励或向合资格参与者提供奖励的灵活手段；通过向合资格参与者提供取得公司所有权权益并成为股东的机会，使合资格参与者的利益与公司及股东的利益保持一致；并鼓励合资格参与者为公司的长期发展、业绩及利润作出贡献，提升公司及其H股的价值，以符合公司及股东的整体利益。对于一家处于管线密集兑现期的18A生物科技公司而言，这项激励计划的时点值得关注。麦科医药于2026年6月24日登陆港交所，成为西北首家依据18A规则上市的创新药企业，也是港股“多肽创新药第一股”。上市至今不到四个月，公司核心管线正从临床阶段向商业化阶段切换，此时推出覆盖十年的激励计划，指向的是核心研发与商业化人才的长期绑定。综合 | 公司公告  编辑 | Arti本文仅为信息交流之用，不构成任何交易建议管线密集兑现：从临床尾声到商业化前夜麦科医药聚焦心脑血管、肾脏及代谢性疾病领域，已构建起由一款核心产品及六款关键候选产品组成的管线矩阵，七款管线进入临床，六款实现中美双报，是国内多肽创新药领域临床阶段管线数量最多且技术领先的企业之一。核心产品MT1013针对慢性肾病继发性甲状旁腺功能亢进症，III期临床试验已完成全部患者入组，预计2027年底提交上市申请、2028年初实现商业化。MT1013采用CaSR/OGP双靶点设计，在与全球最优药物依特卡肽的头对头试验中，iPTH、血钙、血磷综合达标率约为依特卡肽的2.5倍，同时显著降低与心血管风险相关的FGF23水平，该研究数据已被美国肾脏病学会年会收录为“Late-Breaking Science”。关键产品MT200605用于治疗急性缺血性脑卒中，II期临床试验已达到主要终点，展现出显著且稳健的疗效优势及良好安全性。该药物是目前所有进入临床阶段的缺血性卒中治疗药物中唯一能够穿透血脑屏障、靶向BDNF/TrkB通路、具有神经营养作用的小分子激动剂，已入选“创新药物研发国家科技重大专项”，并于2026年3月获美国FDA孤儿药资格认定。XTL6001是全球唯一在中美均获批临床的GLP-1R/GCGR/MasR三重激动剂，I期临床已完成锁库，将治疗维度从单纯的减重、代谢调控拓展至肾脏保护与抗炎抗纤维化。MT1002则是目前全球首个进入临床阶段兼具抗凝和抗血小板聚集双重作用的抗栓多肽药物，通过“一药双靶”协同设计，在抑制血栓形成的同时尽量降低出血风险。四款产品在未来18个月内进入多个关键节点：MT1013预计2026年第四季度完成确证性III期研究并提交pre-NDA会议申请，2027年第一季度提交NDA；MT200605的III期首例入组预计于2027年第一季度前完成；XTL6001预计2026年第四季度入组II期首例患者；MT1002用于血液透析的II期临床试验首名患者已于2026年第三季度入组。现金流转正与资产负债表修复：“研发投入期”到“资金保障+里程碑兑现”管线密集推进的背后，是麦科医药财务状况的结构性改善。2026年上半年，公司经营活动产生的现金流量净额由上年同期的净流出5230万元转为净流入1.092亿元，实现由负转正。这一转折主要得益于与云顶新耀达成的授权合作，2026年2月，公司将MT1013在中国及亚太区（日本除外）的独家商业化权利授予云顶新耀，获得2亿元首付款，未来还有望获得最高10.4亿元的里程碑付款及销售分成，该交易创下近年来中国多肽领域CSO交易首付款及合同总额的纪录。截至2026年6月30日，公司现金及金融资产总额达到12.27亿元，且没有任何银行借款等有息负债，资产负债比率由389.6%降至健康的25.2%。董事会表示，现有资金足以支持公司未来长期研发投入。研发投入方面，上半年研发费用约1.28亿元，同比增长约216%，主要集中于临床阶段产品的推进与四大核心技术平台的持续建设。四大平台包括双/多特异性多肽平台、长效多肽平台、口服多肽平台及多肽偶联药物平台。激励计划与长期价值的绑定逻辑从麦科医药当前所处的阶段来看，十年期H股激励计划的推出有其内在逻辑。在管线从临床尾声向商业化前夜切换的窗口期，公司需要同时留住两类关键人才：推进III期临床和注册申报的临床开发团队，以及筹备商业化落地的市场准入团队。激励计划的有效期设定为十年，覆盖了MT1013从NDA提交到上市后放量、以及后续管线陆续进入商业化阶段的完整周期。同步寻求的10%H股回购授权，则为公司在股价波动时提供了灵活的资本管理工具，回购股份可被注销或持有为库存股，与激励计划形成配套。从股东结构看，公司控股股东王冰博士、王梅博士夫妇合计持股约43.43%，股权结构集中且稳定，为长期激励计划的执行提供了治理基础。从2026年6月上市至今，麦科医药在不到四个月里完成了从“18A新股”到“管线密集兑现期”的切换。MT1013 III期入组完成、MT200605 II期达到主要终点、XTL6001 I期锁库、MT1002进入II期临床，四款产品、多个关键节点的推进节奏，构成了公司当前最核心的价值支撑。12.27亿元现金及金融资产、经营现金流转正、零有息负债的资产负债表，为管线推进提供了财务保障。而十年期H股激励计划的采纳，指向的是在管线兑现的关键窗口期，将核心人才的利益与公司的长期价值增长深度绑定。从“研发投入期”到“价值验证期”，麦科医药正处在一个需要人才、资金和管线节奏三者协同推进的阶段，激励计划的落地恰逢其时。