Parathyroid Hormone(Shire Plc)

编者按：2026年第三季度，多肽疗法在口服大环肽、激素模拟肽等方向取得监管进展，多受体激动、胰淀素联合治疗和降低给药频率的策略也获得新的临床证据。相关研发在探索疗效的同时，也着力改善给药便利性，回应长期治疗需求。为支持创新项目推进，药明康德提供覆盖多肽开发、生产与生物分析的一体化服务。本文将回顾本季度全球多肽疗法在监管审批、临床研究及产业合作等方面的重要进展，带您了解不同技术路线的开发方向与最新动态。 监管进展 本季度，口服多肽的应用除了在体重管理上持续推进外，还进一步延伸至血脂管理。诺和（Novo）于七月宣布，欧盟委员会已批准Wegovy口服片，即每日一次的口服司美格鲁肽（semaglutide）25 mg片剂，用于配合低热量饮食和增加身体活动，帮助肥胖成人，或伴有至少一种体重相关合并症的超重成人进行体重管理。新闻稿指出，此次批准使Wegovy口服片成为欧盟首个获批用于体重管理的口服胰高血糖素样肽-1（GLP-1）受体激动剂。 默沙东（MSD）的口服大环肽PCSK9抑制剂Lipfendra（enlicitide）则在同月获得美国FDA批准，配合饮食和运动，用于降低成人高胆固醇血症患者的低密度脂蛋白胆固醇（LDL-C），适用人群包括杂合子家族性高胆固醇血症患者。 此次批准主要基于3期CORALreef Lipids和CORALreef HeFH研究的结果。两项随机、双盲、安慰剂对照研究分别纳入2904例和303例成人高胆固醇血症患者。在第24周时，CORALreef Lipids研究中enlicitide组患者的LDL-C水平相较安慰剂组降低56%；在CORALreef HeFH研究中，安慰剂校正后的LDL-C降幅为59%。Enlicitide治疗还降低了非高密度脂蛋白胆固醇和载脂蛋白B等与动脉粥样硬化性心血管疾病风险相关的指标。 在血液疾病领域，武田（Takeda）宣布铁调素模拟肽Mimrylo（rusfertide）获得FDA批准，用于治疗成人真性红细胞增多症相关的红细胞增多。该药由Protagonist Therapeutics发现并推进至3期临床开发，武田拥有全球独家开发和商业化权利。 批准依据为VERIFY临床3期研究的结果，该研究共纳入293例真性红细胞增多症成人患者。疗效通过研究第20周至第32周期间未达到放血治疗标准的患者比例进行评估。分析显示，接受每周一次皮下注射Mimrylo联合标准治疗的患者中，76.9%在第20-32周达到该主要应答终点。 临床进展 围绕肥胖及相关代谢疾病，多受体激动肽继续积累关键人体证据。礼来（Eli Lilly and Company）的三重激素受体激动剂retatrutide，在TRIUMPH-2和TRIUMPH-3两项3期研究中达到主要体重终点。两项研究分别随机纳入1152名肥胖或超重伴2型糖尿病患者，以及1949名重度肥胖伴既有心血管疾病患者。在疗效估计目标下，每周一次12 mg组治疗80周后的平均体重降幅分别为20.8%和22.6%，安慰剂组分别为4.0%和3.2%。Retatrutide是一款每周给药一次的单分子疗法，可同时激活葡萄糖依赖性促胰岛素多肽（GIP）、GLP-1和胰高血糖素受体。 胰淀素相关方案为联合治疗提供了另一组证据。诺和的CagriSema由长效胰淀素类似物cagrilintide与GLP-1受体激动剂司美格鲁肽组成。对REIMAGINE 5临床3期研究中两项主要终点糖化血红蛋白（HbA1c）和体重变化的分析显示，CagriSema组第60周平均体重降幅为12.4%，活性对照组为9.1%，在体重主要终点上达到统计学优效性。HbA1c平均降幅则分别为1.71个百分点和1.67个百分点，CagriSema达到非劣效性标准。 礼来的EloraTZP是一项将选择性胰淀素受体激动剂eloralintide与GIP/GLP-1双受体激动剂替尔泊肽（tirzepatide）联合使用的在研治疗方案。近期公布的2b期研究结果显示，第48周时，不同EloraTZP剂量组合的平均体重降幅为13.2%～23.3%，安慰剂组为3.0%；最高剂量组合的平均体重降幅为23.3%，活性对照组为14.8%。接受不同EloraTZP剂量组合患者的HbA1c平均下降2.2～2.9个百分点，活性对照组则下降2.4个百分点。 降低给药频率也是本季度值得观察的方向。Viking Therapeutics的GIP/GLP-1双受体激动剂VK2735，在完成21周的每周给药诱导治疗后，进一步评估了12周隔周或每月给药的维持效果。隔周给药组和每月给药组的疗效分析人群分别为37人和65人，对照组为27人。在特定剂量亚组中，隔周给药和每月给药分别最高可维持诱导期平均减重量的97%和90%，安慰剂组为61%。 与此同时，Zealand Pharma与罗氏（Roche）在9月启动petrelintide的全球3期注册性项目ZUPREME。这一长效胰淀素类似物将以每周一次给药，在三项研究中计划纳入约7000人，主要评价在第64周受试者的体重变化。 在更早期的开发阶段中，勃林格殷格翰（Boehringer Ingelheim）与Gubra合作开发的BI 3034701进入2期临床试验，探索GLP-1、GIP与NPY2受体的联合激动策略。该研究将开展剂量探索及疗效、安全性评价。歌礼制药的口服胰淀素受体激动肽ASC36则在获得美国FDA允许开展临床试验后，启动1期研究，计划纳入86名肥胖或超重受试者。 此外，多肽疗法的开发方向也延伸至体重管理之外。Amylyx的GLP-1受体拮抗肽avexitide，在78名减重手术后低血糖（PBH）患者参与的LUCIDITY临床3期研究中达到主要终点。患者接受治疗16周后，2级和3级低血糖事件复合发生率较安慰剂降低55%。该项目展现了抑制GLP-1作用在肥胖以外疾病中的治疗潜力。 Altimmune的双受体激动肽pemvidutide则在酒精使用障碍（AUD）领域公布RECLAIM临床2期结果。该试验达到主要终点：与安慰剂相比，pemvidutide可减少重度饮酒天数（HDD），差异具有统计学显著性。基于该试验结果，公司计划向美国FDA申请召开2期临床试验结束会议。Pemvidutide是一款新型在研多肽，具有平衡的胰高血糖素/GLP-1双受体激动活性。 在激素替代治疗方面，MBX Biosciences的长效甲状旁腺激素（PTH）肽前药canvuparatide完成注册性3期oPTimize研究首例患者给药。研究面向慢性甲状旁腺功能减退症，评价每周给药能否在维持正常血钙的同时，减少钙和活性维生素D补充需求。 研发合作与并购进展 产业合作方面，韩美医药（Hanmi Pharmaceutical）与罗氏旗下基因泰克（Genentech），就HM17321达成除韩国外的全球独家许可协议，协议潜在总额最高达23亿美元。HM17321是一款长效尿皮质素2（urocortin-2，UCN2）类似物，目前正在美国开展1期临床研究。 Telix Pharmaceuticals与ITM Isotope Technologies Munich（ITM）已签署战略合并协议，Telix拟收购ITM的全部股权。交易完成后，Telix有望进一步整合放射性同位素供应、药物研发及生产能力，为其放射性药物管线的后续开发和商业化提供支持。ITM的核心项目ITM-11（¹⁷⁷Lu-edotreotide）是一款靶向生长抑素受体（SSTR）的镥-177标记多肽放射性偶联药物，正在开发用于治疗胃肠胰神经内分泌肿瘤（GEP-NETs）。该药已完成3期临床试验COMPETE，另一项适应症拓展3期研究COMPOSE也已完成患者入组，预计于2027年上半年进行中期分析。 从分子开发到生物分析的一体化支持 药明康德旗下WuXi TIDES多肽平台为原料药和制剂提供从药物发现到商业化生产的一体化合同研究、开发和生产（CRDMO）服务。由数百名研发人员组成的多肽开发团队，支持长肽、环肽、复杂修饰肽、非天然氨基酸及偶联药物的工艺开发，并通过跨职能协作衔接工艺研究与放大生产。平台采用定制合成设备和裂解反应釜，降低微生物污染及交叉污染风险，结合液相多肽合成、连续反应釜、连续流动色谱、切向流过滤及沉淀等技术，依托符合全球标准的质量体系，提供克级至吨级的多肽原料药供应。 随着多肽分子量增加、结构修饰增多及偶联形式日益复杂，其生物分析面临信号分散、离子抑制和内源性干扰等挑战。表位有限及与内源性肽的高同源性，也增加了特异性抗体制备和免疫原性评价的难度；脂肪酸修饰、PEG化或蛋白融合虽可延长半衰期，也可能引入新的免疫原性风险。 针对这些挑战，药明康德生物分析部（BAS）整合高灵敏度液相色谱串联质谱（LC-MS/MS）、免疫捕获-质谱、酶联免疫吸附分析（ELISA）、电化学发光分析及细胞功能分析方法，支持药代动力学（PK）研究和免疫原性评价。通过优化样本前处理及采用基于胰蛋白酶消化的bottom-up分析方法，提升检测灵敏度并降低基质干扰。在免疫原性评价方面，平台以桥式抗药抗体（ADA）检测、确认试验和滴度分析构建分层评价体系，结合酸解离、最小要求稀释倍数（MRD）优化及标记试剂设计，降低药物干扰、内源性干扰与非特异性结合，并通过细胞功能性中和抗体（NAb）分析评价中和效应。 该生物分析平台已支持GLP-1类似物、胰岛素类似物等药物的临床PK研究及免疫原性评估，覆盖方法开发、验证和样本检测，为合作伙伴提供支持研发决策的可靠分析数据，助力创新多肽疗法的临床开发。 总结与展望 总体来看，2026年第三季度多肽疗法在口服给药、多靶点协同及长效治疗等方向取得多项进展。一方面，口服大环肽、铁调素模拟肽获得监管批准，为高胆固醇血症、真性红细胞增多症患者增加治疗选择；另一方面，肥胖及代谢疾病领域的双重与三重受体激动剂、胰淀素联合方案持续积累临床证据，降低给药频率的策略也进入人体验证。同时，术后低血糖、酒精使用障碍及甲状旁腺功能减退症等领域的进展，展现了多肽疗法更广泛的应用潜力。随着注册性研究推进及产业合作展开，如何兼顾疗效、耐受性与给药便利性，并将研发成果转化为可持续供应的治疗方案，将成为后续发展的重要看点。 Q3 2026 Review: Peptide Therapeutics In the third quarter of 2026, peptide therapeutics achieved regulatory progress in areas including oral macrocyclic peptides and hormone-mimetic peptides. New clinical evidence also emerged for multi-receptor agonism, amylin-based combination therapies, and strategies to reduce dosing frequency. Alongside evaluating efficacy, these development efforts seek to improve dosing convenience and address long-term treatment needs. To support the advancement of innovative programs, WuXi AppTec provides integrated services spanning peptide development, manufacturing, and bioanalysis. This article reviews important global developments in regulatory approvals, clinical research, and industry partnerships during the quarter, highlighting the development directions and latest advances across different therapeutic approaches. Regulatory Developments This quarter, oral peptides continued to advance in weight management while expanding further into lipid management. In July, Novo announced that the European Commission had approved Wegovy tablets, a once-daily oral formulation of semaglutide at a dose of 25 mg, for weight management in adults with obesity or adults with overweight and at least one weight-related comorbidity, as an adjunct to a reduced-calorie diet and increased physical activity. According to the press release, this approval made Wegovy tablets the first oral glucagon-like peptide-1 (GLP-1) receptor agonist approved for weight management in the European Union. In the same month, MSD’s oral macrocyclic peptide PCSK9 inhibitor Lipfendra (enlicitide) received U.S. FDA approval as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including those with heterozygous familial hypercholesterolemia. The approval was primarily supported by results from the Phase 3 CORALreef Lipids and CORALreef HeFH trials. These randomized, double-blind, placebo-controlled studies enrolled 2,904 and 303 adults with hypercholesterolemia, respectively. At Week 24, enlicitide reduced LDL-C by 56% compared with placebo in CORALreef Lipids, while the placebo-adjusted LDL-C reduction in CORALreef HeFH was 59%. Enlicitide also reduced other measures associated with atherosclerotic cardiovascular disease risk, including non-high-density lipoprotein cholesterol and apolipoprotein B. In hematology, Takeda announced FDA approval of Mimrylo (rusfertide), a hepcidin-mimetic peptide, for the treatment of erythrocytosis in adults with polycythemia vera. Protagonist Therapeutics discovered the drug and advanced it through Phase 3 development. Takeda holds exclusive global development and commercialization rights. The approval was based on results from the Phase 3 VERIFY trial, which enrolled 293 adults with polycythemia vera. Efficacy was assessed by the proportion of patients who did not meet the criteria for phlebotomy eligibility during Weeks 20–32. The analysis showed that 76.9% of patients receiving once-weekly subcutaneous Mimrylo alongside standard-of-care treatment met this primary response endpoint during that period. Clinical Developments Multi-receptor agonist peptides continued to generate important clinical evidence in obesity and related metabolic diseases. Eli Lilly and Company’s triple hormone receptor agonist retatrutide met the primary weight endpoint in two Phase 3 trials, TRIUMPH-2 and TRIUMPH-3. The studies randomized 1,152 participants with obesity or overweight and type 2 diabetes, and 1,949 participants with severe obesity and established cardiovascular disease, respectively. Under the efficacy estimand, mean weight reductions after 80 weeks in the once-weekly 12 mg groups were 20.8% and 22.6%, respectively, compared with 4.0% and 3.2% in the placebo groups. Retatrutide is a once-weekly, single-molecule therapy that activates the receptors for glucose-dependent insulinotropic polypeptide (GIP), GLP-1, and glucagon. Amylin-based approaches provided additional evidence for combination therapy. Novo’s CagriSema combines the long-acting amylin analog cagrilintide with the GLP-1 receptor agonist semaglutide. An analysis of the two primary endpoints—changes in glycated hemoglobin (HbA1c) and body weight—in the Phase 3 REIMAGINE 5 trial showed a mean weight reduction of 12.4% at Week 60 in the CagriSema group, compared with 9.1% in the active comparator group, demonstrating statistically significant superiority for the weight endpoint. Mean HbA1c reductions were 1.71% and 1.67%, respectively, with CagriSema meeting the criterion for non-inferiority. Lilly’s EloraTZP is an investigational regimen combining the selective amylin receptor agonist eloralintide with tirzepatide, a dual GIP/GLP-1 receptor agonist. Recently announced Phase 2b results showed mean weight reductions ranging from 13.2% to 23.3% across EloraTZP dose combinations at Week 48, compared with 3.0% with placebo. The highest-dose combination produced a mean weight reduction of 23.3%, compared with 14.8% in the active comparator group. Mean HbA1c reductions across the EloraTZP dose combinations ranged from 2.2% to 2.9%, compared with 2.4 percentage points in the active comparator group. Reducing dosing frequency was another area of interest during the quarter. A study of Viking Therapeutics’ dual GIP/GLP-1 receptor agonist VK2735 evaluated weight maintenance over 12 weeks of every-other-week or monthly dosing following a 21-week induction period with weekly dosing. The efficacy analysis populations included 37 participants in the every-other-week group, 65 in the monthly group, and 27 in the control group. In specific dose subgroups, every-other-week and monthly dosing maintained 97% and 90%, respectively, of the mean weight loss achieved during induction, compared with 61% with placebo. Meanwhile, Zealand Pharma and Roche initiated the global Phase 3 ZUPREME registrational program for petrelintide in September. The program will evaluate once-weekly administration of this long-acting amylin analog across three trials, with approximately 7,000 participants planned for enrollment. The primary assessment will evaluate participants’ weight change at Week 64. At an earlier stage of development, BI 3034701, developed jointly by Boehringer Ingelheim and Gubra, entered Phase 2 to investigate combined agonism of the GLP-1, GIP, and NPY2 receptors. The study will evaluate dose selection, efficacy, and safety. Ascletis also initiated a Phase 1 study of ASC36, its oral amylin receptor peptide agonist, following FDA clearance to conduct clinical testing. The study plans to enroll 86 participants with obesity or overweight. Peptide development also extended beyond weight management. Amylyx’s GLP-1 receptor antagonist peptide avexitide met the primary endpoint in the Phase 3 LUCIDITY trial, which enrolled 78 patients with post-bariatric hypoglycemia (PBH). After 16 weeks of treatment, the composite rate of Level 2 and Level 3 hypoglycemic events was 55% lower than with placebo. The program illustrates the potential of inhibiting GLP-1 activity to treat conditions beyond obesity. Altimmune announced Phase 2 RECLAIM results for its dual receptor agonist peptide pemvidutide in alcohol use disorder (AUD). The trial met its primary endpoint, with pemvidutide producing a statistically significant reduction in heavy drinking days (HDD) compared with placebo. Based on these findings, the company plans to request an End-of-Phase 2 meeting with the FDA. Pemvidutide is a novel investigational peptide with balanced glucagon/GLP-1 dual receptor agonist activity. In hormone replacement therapy, MBX Biosciences dosed the first patient in the registrational Phase 3 oPTimize trial of canvuparatide, a long-acting parathyroid hormone (PTH) peptide prodrug. The study is evaluating whether once-weekly treatment can maintain normal serum calcium levels while reducing the need for calcium and active vitamin D supplementation in patients with chronic hypoparathyroidism. R&D Partnerships, Mergers and Acquisitions In industry partnerships, Hanmi Pharmaceutical entered into an exclusive licensing agreement with Roche’s Genentech for worldwide rights to HM17321 outside South Korea, with a potential total of up to US$2.3 billion. HM17321 is a long-acting urocortin-2 (UCN2) analog currently being evaluated in a Phase 1 clinical study in the United States. Telix Pharmaceuticals and Isotope Technologies Munich (ITM) signed a strategic merger agreement under which Telix intends to acquire all of ITM’s equity. Following completion, the transaction is expected to enable Telix to further integrate radioisotope supply, drug development, and manufacturing capabilities to support the continued development and commercialization of its radiopharmaceutical pipeline. ITM’s lead program, ITM-11 (¹⁷⁷Lu-edotreotide), is a lutetium-177-labeled peptide radioconjugate targeting somatostatin receptors (SSTRs), in development for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The drug has completed the Phase 3 COMPETE trial. A second Phase 3 study supporting indication expansion, COMPOSE, has also completed enrollment, with an interim analysis expected in the first half of 2027. Integrated Support from Molecular Development to Bioanalysis WuXi AppTec’s WuXi TIDES peptide platform provides integrated contract research, development, and manufacturing (CRDMO) services for active pharmaceutical ingredients (APIs) and drug products, spanning drug discovery through commercial manufacturing. Its peptide development team, comprising hundreds of R&D professionals, supports process development for long peptides, cyclic peptides, complex modified peptides, non-natural amino acids, and conjugated therapeutics. Cross-functional collaboration connects process research with manufacturing scale-up. The platform uses customized synthesis equipment and cleavage reactors to reduce the risk of microbial contamination and cross-contamination. Combining technologies such as liquid-phase peptide synthesis, continuous stirred-tank reactors, continuous-flow chromatography, tangential flow filtration, and precipitation, it provides peptide API supply from gram to metric-ton scale under a quality system aligned with global standards. As peptide molecular weight increases and structural modifications and conjugation formats become more complex, bioanalysis faces challenges including signal dispersion, ion suppression, and endogenous interference. Limited epitopes and high sequence homology with endogenous peptides also complicate the generation of specific antibodies and the assessment of immunogenicity. Although fatty acid modification, PEGylation, and protein fusion can extend half-life, they may also introduce new immunogenicity risks. To address these challenges, WuXi AppTec’s Bioanalytical Services (BAS) integrates high-sensitivity liquid chromatography–tandem mass spectrometry (LC-MS/MS), immunocapture–mass spectrometry, enzyme-linked immunosorbent assays (ELISA), electrochemiluminescence assays, and cell-based functional assays to support pharmacokinetic (PK) studies and immunogenicity assessment. Optimized sample preparation and trypsin digestion-based bottom-up analytical methods improve detection sensitivity and reduce matrix interference. For immunogenicity assessment, the platform uses bridging anti-drug antibody (ADA) assays, confirmatory testing, and titer analysis within a tiered framework. Acid dissociation, optimization of the minimum required dilution (MRD), and labeled reagent design help reduce drug interference, endogenous interference, and nonspecific binding. Cell-based functional neutralizing antibody (NAb) assays are used to assess neutralizing activity. The bioanalytical platform has supported clinical PK studies and immunogenicity assessments for therapies including GLP-1 analogs and insulin analogs. Its capabilities span method development, validation, and sample analysis, providing partners with reliable analytical data to inform R&D decisions and support the clinical development of innovative peptide therapeutics. Summary and Outlook Overall, peptide therapeutics achieved multiple advances in oral delivery, multi-target approaches, and long-acting treatment during the third quarter of 2026. Oral macrocyclic peptides and hepcidin-mimetic peptides received regulatory approval, expanding treatment options for patients with hypercholesterolemia and polycythemia vera. In obesity and metabolic diseases, dual and triple receptor agonists and amylin-based combination regimens continued to generate clinical evidence, while strategies to reduce dosing frequency also underwent clinical evaluation. Progress in post-bariatric hypoglycemia, alcohol use disorder, and hypoparathyroidism further demonstrated the broader potential applications of peptide therapeutics. As registrational studies and industry partnerships advance, key areas to watch will include balancing efficacy, tolerability, and dosing convenience, and translating R&D progress into treatment options supported by reliable, sustained supply. 参考资料： 各家公司官方网站 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

COPENHAGEN, Denmark, Oct. 06, 2026 (GLOBE NEWSWIRE) -- Ascendis Pharma A/S (Nasdaq: ASND) today announced that the latest advances in its hypoparathyroidism and achondroplasia programs will be showcased during ASBMR 2026, the annual meeting of American Society for Bone & Mineral Research being held in Boston from October 9-12, 2026. Updates include an oral presentation by Aliya Khan, M.D., of combined skeletal data from the Phase 2 PaTH Forward and Phase 3 PaTHway trials showing normalization of bone mass and microarchitecture in clinical trial patients treated with TransCon® PTH (palopegteriparatide) over a 5-year period. “Our growing body of clinical trial data continues to illustrate the unique potential for our differentiated TransCon-based therapies to improve patient health and quality of life,” said Aimee Shu, M.D., Executive Vice President, Chief Medical Officer at Ascendis Pharma. “Compelling long-term data such as these help inform treatment paradigms focused on outcomes that matter most to patients, and we look forward to sharing additional results as our programs advance.” Ascendis presentations at ASBMR 2026: ORAL PRESENTATIONHypoparathyroidismSunday, Oct. 11Session: 11:30a.m.-12:30p.m.Presentation: 12:18 PM – 12:30 Calcium Homeostasis DisordersBallroom A&BID #6080: Long-Term Effects of Palopegteriparatide on BMD and TBS in Adults With Chronic Hypoparathyroidism: Pooled Results from the PaTH Forward and PaTHway TrialsPresented by Aliya Khan, M.D.POSTERS HypoparathyroidismThursday, Oct. 85:30-6:30p.m.ASBMR/RBDA Pre-Meeting Symposium---Sunday, Oct. 112:00-3:00p.m.Poster Session IIID #6680: Hypoparathyroidism: Understanding the Impact of Palopegteriparatide on Patients’ Health Related Quality of Life, Functioning, and Well-Being Presented by Meryl Brod, Ph.D.AchondroplasiaFriday, Oct. 95:30-7:00p.m.Plenary Poster Session---Saturday, Oct. 102:00-3:30pm Poster Session 1ID 6329: Improved Growth and Physical Functioning in Children with Achondroplasia Treated with Navepegritide in the ApproaCH Trial Open-Label ExtensionPresented by Ciara McDonnell, M.D.Thursday, Oct. 85:30-6:30p.m.ASBMR/RBDA Pre-Meeting Symposium ---Friday, Oct. 95:30-7:00p.m.Plenary Poster Session---Saturday, Oct. 102:00-3:30pm Poster Session IID 6320: Continued Improvements in Lower Extremity Alignment in Navepegritide-Treated Children With Achondroplasia: Week 104 Results from the ApproaCH TrialPresented by Leanne Ward, M.D.Sunday, Oct. 112:00-3:00p.m.Late BreakingPoster Session IILate Breaker ID 8736: Navepegritide Combined with Lonapegsomatropin for the Treatment of Children with Achondroplasia: 78-Week Results from the Phase 2 COACH Trial Presented by Ciara McDonnell, M.D. About TransCon PTH TransCon PTH (palopegteriparatide) is a prodrug of PTH (1-34), administered once daily, designed to provide stable levels of active PTH within the physiological range for 24 hours/day. TransCon CNP is approved as YORVIPATH® in the United States (U.S.), European Union (EU), European Economic Area (EEA), and certain other jurisdictions as a treatment for adults with hypoparathyroidism. About TransCon CNPTransCon CNP (navepegritide) is a prodrug of C-type natriuretic peptide (CNP) administered once weekly, designed to provide continuous exposure of active CNP to receptors on tissues throughout the body to counteract the overactive FGFR3 signaling in achondroplasia. TransCon CNP is approved as YUVIWEL® in the U.S. as a treatment for children with achondroplasia. Ascendis Pharma’s Marketing Authorisation Application for YUVIWEL is under review by the European Medicines Agency, with a decision anticipated in the fourth quarter of 2026. About TransCon hGHTransCon hGH (lonapegsomatropin) is a prodrug of somatropin administered once weekly, providing sustained release of active, unmodified somatropin. TransCon hGH is investigational in achondroplasia and is approved as SKYTROFA® in the U.S., EU, EEA, and elsewhere for the treatment of growth failure in children due to growth hormone deficiency and in the U.S. for the replacement of endogenous growth hormone in adults with growth hormone deficiency. About HypoparathyroidismHypoparathyroidism is an endocrine disease caused by insufficient levels of parathyroid hormone (PTH), the primary regulator of calcium and phosphate balance in the body, acting directly on bone and kidney and indirectly on the intestine. Individuals with hypoparathyroidism may experience a range of severe and potentially life-threatening short-term and long-term complications, including neuromuscular irritability, renal complications, extra-skeletal calcifications, and cognitive impairment. Post-surgical hypoparathyroidism accounts for the majority of cases (70-80%), while other etiologies include autoimmune, idiopathic, and genetic causes, including ADH1. About AchondroplasiaAchondroplasia is a rare genetic condition arising from a systemic fibroblast growth factor receptor 3 (FGFR3) variant that leads to an imbalance in the effects of the FGFR3 and CNP signaling pathways, estimated to affect more than 250,000 people worldwide. While historically considered a bone growth disorder, the FGFR3 variant seen in achondroplasia is expressed in tissues throughout the body, causing serious muscular, neurological, and cardiorespiratory complications in addition to skeletal dysplasia. Medical complications of achondroplasia vary across different stages of life. Throughout infancy and childhood, observed complications include spinal abnormalities, enlarged brain ventricles, impaired muscle strength and stamina, hearing deficits and chronic ear infections, upper airway obstructions, sleep-disordered breathing, hip problems, leg bowing, and chronic pain; many of these persist or worsen in adulthood. These medical complications can affect physical well-being and quality of life, and may be impacted by a range of individual, clinical, and social factors. Some individuals with achondroplasia require multiple procedures and surgeries to address specific functional or anatomical concerns. About Ascendis Pharma A/SAscendis Pharma is a global biopharmaceutical company focused on applying our innovative TransCon technology platform to make a meaningful difference for patients. Guided by our core values of Patients, Science, and Passion, and following our algorithm for product innovation, we apply TransCon to develop new therapies that demonstrate best-in-class potential to address unmet medical needs. Ascendis is headquartered in Copenhagen, Denmark, and has additional facilities in Europe and the United States. Please visit ascendispharma.com to learn more. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, included in this press release regarding Ascendis’ future operations, plans and objectives of management are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Examples of such statements include, but are not limited to, statements relating to (i) Ascendis’ planned oral presentation and posters at ASBMR 2026, (ii) the combined skeletal data from the Phase 2 PaTH Forward and Phase 3 PaTHway trials, including normalization of bone mass and microarchitecture in clinical trial patients treated with TransCon PTH (palopegteriparatide) over a 5-year period, (iii) the unique potential for Ascendis’ highly differentiated TransCon-based therapies to improve patient health and quality of life, (iv) the potential for long-term data to help inform treatment paradigms focused on outcomes that matter most to patients, (v) Ascendis’ plan to share additional results as its programs advance, (vi) Ascendis’ clinical development activities, including the ApproaCH Trial open-label extension and the Phase 2 COACH Trial of navepegritide combined with lonapegsomatropin, (vii) Ascendis’ ability to apply its TransCon technology platform to make a meaningful difference for patients and (viii) Ascendis’ use of TransCon to create new and potentially best-in-class therapies to address unmet medical needs. Ascendis may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions, expectations and projections disclosed in the forward-looking statements. Various important factors could cause actual results or events to differ materially from the forward-looking statements that Ascendis makes, including, without limitation: dependence on third‑party manufacturers, distributors, and service providers for Ascendis’ products and product candidates; risks related to regulatory review and approval, including the possibility of delays, requests for additional data or analyses, restrictions or limitations on use, approval with labeling that is more limited than expected, or failure to obtain approval in the United States, European Union, or other jurisdictions; clinical development risks, including that results from ongoing or future trials may not confirm earlier data; unforeseen safety or efficacy findings in development programs or on‑market products; manufacturing, supply chain, quality, or logistics issues that could delay development or commercialization; unforeseen expenses related to commercialization of any approved Ascendis products; unforeseen research and development or selling, general and administrative expenses and other costs impacting Ascendis’ business generally; market acceptance, pricing, and reimbursement challenges, including payer coverage decisions and health technology assessments; competitive developments, including new or improved therapies; intellectual property protection, freedom‑to‑operate, and litigation risks; Ascendis’ ability to obtain additional funding, if needed, to support its business activities; cybersecurity, data privacy, and information technology disruptions; and the impact of international economic, political, legal, compliance, public health, and business factors, including tariffs, trade policies, currency fluctuations, and geopolitical events. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Ascendis’ business in general, see Ascendis’ Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission (SEC) on February 11, 2026, and Ascendis’ other future reports filed with, or submitted to, the SEC. Forward-looking statements do not reflect the potential impact of any future licensing, collaborations, acquisitions, mergers, dispositions, joint ventures, or investments that Ascendis may enter into or make. Ascendis does not assume any obligation to update any forward-looking statements, except as required by law. Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo, TransCon, SKYTROFA®, YORVIPATH®, and YUVIWEL® are trademarks owned by the Ascendis Pharma group. © October 2026 Ascendis Pharma A/S. Investor Contact:Media Contact:Chad FugereMelinda BakerAscendis PharmaAscendis Pharma+1 (650) 519-7494+1 (650) 709-8875