TERN-601

▎药明康德本期看点1. ROS1选择性抑制剂zidesamtinib用于接受过酪氨酸激酶抑制剂（TKI）治疗的晚期ROS1阳性非小细胞肺癌（NSCLC）患者，在一项1/2期临床试验中取得积极结果，其上市申请递交在即。2. 早期数据表明，罗氏（Roche）的在研双特异性抗体NXT007有望使血友病A患者的凝血功能恢复正常。3. 用于治疗慢性乙型肝炎病毒（HBV）感染的下一代衣壳组装调节剂ABI-4334在1b期临床试验中展现强力的抗病毒活性，高剂量组患者接受治疗28天，血浆HBV DNA平均降低3.2 log IU/mL。NXT007：公布1/2期临床试验数据罗氏宣布，其新一代在研双特异性抗体NXT007在治疗血友病A的1/2期临床试验中取得积极数据，将推进至3期临床试验。NXT007由罗氏旗下的Chugai Pharmaceutical公司研发，基于已上市药物Hemlibra的框架优化设计，旨在模拟因子VIII功能，同时延长半衰期，提高疗效和用药便利性。该药通过将凝血因子IXa和X桥接在一起，激活体内自然凝血级联反应，有望使血友病A患者的凝血功能恢复正常，并减少治疗负担。在这项研究中，30名12至65岁、无因子VIII抑制剂，且既往未接受过Hemlibra治疗的血友病A患者在接受了4至6周的负荷剂量后，在维持期每2至4周皮下注射递增剂量的NXT007。结果显示，高剂量组（B-3和B-4）的患者在整个维持期内均保持止血正常化状态，未出现需治疗的出血事件。安全性方面，NXT007的耐受良好，目前未报告血栓栓塞事件。Zidesamtinib：公布1/2期临床试验数据Nuvalent公司公布了其新型ROS1选择性抑制剂zidesamtinib在1/2期临床试验ARROS-1中的关键积极数据。该试验针对接受过TKI治疗的晚期ROS1阳性NSCLC患者。Zidesamtinib是一种具脑渗透性的ROS1抑制剂，设计用以治疗那些对现有ROS1抑制剂具抗性的癌症，包含那些带有G2032R、S1986Y/F、L2026M或D2033N突变的肿瘤。结果显示，在117例曾接受过TKI治疗的ROS1阳性NSCLC患者中（其中50%曾接受过≥2种ROS1 TKI±化疗），由盲态独立中心审查（BICR）评估的客观缓解率（ORR）为44%，初步估计的缓解持续率在12个月时为78%，18个月时为62%。在其中55名曾接受过1种ROS1 TKI（克唑替尼或恩曲替尼）±化疗的患者中，ORR为51%，初步估计的缓解持续率在12和18个月时均为93%。Zidesamtinib还显示出颅内抗肿瘤活性，对携带ROS1 G2032R耐药突变的肿瘤也有作用，整体安全性良好，剂量减少和停药的比例较低，分别为10%和2%。该公司计划于2025年7月启动滚动提交zidesamtinib的新药申请（NDA），目标在2025年第三季度完成。ABI-4334：公布1b期临床试验数据Assembly Biosciences公司公布了其在研下一代衣壳组装调节剂ABI-4334用于治疗慢性HBV感染患者的1b期临床试验数据。此前公布的150 mg剂量组的结果显示，ABI-4334显示出很强的抗病毒活性，在28天的治疗中，血浆HBV DNA平均降低了2.9 log IU/mL。此次公布的400 mg剂量组的结果类似于先前的报道，在28天的治疗中，血浆HBV DNA平均降低了3.2 log IU/mL。此外，在400 mg剂量下继续观察到ABI-4334良好的安全性和耐受性，半衰期支持每日一次口服给药。TERN-601：公布1期临床试验数据Terns Pharmaceuticals公司公布了其每日一次在研减重疗法TERN-601在肥胖或超重健康成年人中进行的1期试验积极结果。TERN-601是一种口服小分子胰高血糖素样肽-1（GLP-1）受体激动剂，由Terns内部研发。TERN-601通过Terns内部基于结构的药物研发技术设计，采用该公司专有的三维定量构效关系（QSAR）模型所开发。此次公布的结果显示，TERN-601在治疗肥胖方面表现出显著的疗效和良好的安全性。在28天内，每日一次给药可实现统计学显著且呈剂量依赖性的体重减轻。在最高剂量组中，有67%的患者体重减轻≥5%。其独特的药代动力学特性使其在24小时内维持平稳的血药浓度曲线，有效半衰期为9-10小时，支持每日一次给药。此外，药物在肠道中的暴露量高于血浆，且游离药物比例低，从而在不牺牲耐受性的前提下实现了有意义的体重减轻。安全性方面，未出现因治疗导致的中断、减量或停药，＞95%的胃肠道不良事件为轻度，患者的肝酶、生命体征和心电图均无明显变化。ENT-03：公布1a期临床试验数据Metabolics Pharma公司公布了其候选药物ENT-03在肥胖和糖尿病患者中开展的1a期临床试验的的初步结果。该研究数据显示，在所有测试剂量下，ENT-03均表现出良好的安全性和耐受性。在较高剂量组中，ENT-03在减轻体重和提高胰岛素敏感性方面呈现出积极趋势。ENT-03是一种新型中枢神经系统作用的氨基类固醇化合物，具有蛋白酪氨酸磷酸酶1B（PTP1B）抑制活性。它通过作用于大脑中调控能量代谢和血糖平衡的神经回路，达到调节葡萄糖水平、改善胰岛素敏感性并促进体重减轻的效果。临床前研究表明，ENT-03作为单药疗法有效，并且在与GLP-1受体激动剂联合使用时表现出累加效应。此外，ENT-03在停药后仍可维持较长时间的体重降低以及血糖和胰岛素水平的正常化。APR-1051：公布联合治疗1期试验的初步数据Aprea Therapeutics公司公布了其下一代口服WEE1抑制剂APR-1051治疗HPV阳性头颈部鳞状细胞癌患者的新临床数据。APR-1051是一种口服、高选择性的WEE1抑制剂，旨在最大限度地减少脱靶活性并优化药理选择性。该疗法目前正在1期临床试验ACESOT-1051中对携带DDR相关通路基因突变（DDR）的晚期实体瘤患者进行评估。该试验中，一名62岁HPV阳性的晚期口咽鳞状细胞癌男性患者，既往接受过三线铂类治疗后进展，在接受每日口服一次70 mg亚治疗剂量的APR-1051后实现疾病稳定，首次影像学评估时肿瘤缩小了5%。该患者对治疗的耐受性良好，未报告剂量限制性毒性。参考资料（可上下滑动查看）[1] LOMOND THERAPEUTICS ANNOUNCES U.S. FDA CLEARANCE OF IND APPLICATION FOR LONITOCLAX, A SELECTIVE BCL2 INHIBITOR WITH LIMITED IMMUNE SUPPRESSION AND IMPROVED SAFETY COMPARED TO VENETOCLAX AND VENETOCLAX- LIKE MOLECULES. Retrieved June 27, 2025, from https://www.prnewswire.com/news-releases/lomond-therapeutics-announces-us-fda-clearance-of-ind-application-for-lonitoclax-a-selective-bcl2-inhibitor-with-limited-immune-suppression-and-improved-safety-compared-to-venetoclax-and-venetoclax--like-molecules-302487020.html[2] Archeus Technologies Receives FDA Clearance of Investigational New Drug Application for ART-101 in Development for the Treatment of Prostate Cancer. Retrieved June 27, 2025, from https://www.businesswire.com/news/home/20250620911569/en/Archeus-Technologies-Receives-FDA-Clearance-of-Investigational-New-Drug-Application-for-ART-101-in-Development-for-the-Treatment-of-Prostate-Cancer[3] Terns Pharmaceuticals Presents Positive Data from Phase 1 Study of TERN-601 Once-daily Oral GLP-1R Agonist for Treatment of Obesity at 85th Annual American Diabetes Association Scientific Sessions. Retrieved June 27, 2025, from https://www.globenewswire.com/news-release/2025/06/23/3103837/0/en/Terns-Pharmaceuticals-Presents-Positive-Data-from-Phase-1-Study-of-TERN-601-Once-daily-Oral-GLP-1R-Agonist-for-Treatment-of-Obesity-at-85th-Annual-American-Diabetes-Association-Sci.html[4] Forte Biosciences Announces Positive Data in FB102 Celiac Disease Phase 1B Study. Retrieved June 27, 2025, from https://www.fortebiorx.com/investor-relations/news/news-details/2025/Forte-Biosciences-Announces-Positive-Data-in-FB102-Celiac-Disease-Phase-1B-Study/default.aspx[5] Nuvalent Announces Positive Pivotal Data from ARROS-1 Clinical Trial of Zidesamtinib for TKI Pre-treated Patients with Advanced ROS1-positive NSCLC. Retrieved June 27, 2025, from https://investors.nuvalent.com/2025-06-24-Nuvalent-Announces-Positive-Pivotal-Data-from-ARROS-1-Clinical-Trial-of-Zidesamtinib-for-TKI-Pre-treated-Patients-with-Advanced-ROS1-positive-NSCLC[6] Cellarity Initiates Phase 1 Clinical Study of CLY-124, a First-in-Class Globin-Switching Oral Medicine for the Treatment of Sickle Cell Disease. Retrieved June 24, 2025 from https://www.prnewswire.com/news-releases/cellarity-initiates-phase-1-clinical-study-of-cly-124-a-first-in-class-globin-switching-oral-medicine-for-the-treatment-of-sickle-cell-disease-302492168.html[7] Contineum Therapeutics Provides Update on Phase 1b Positron Emission Tomography (PET) Trial of PIPE-791. Retrieved June 24, 2025 from https://www.businesswire.com/news/home/20250625697950/en/Contineum-Therapeutics-Provides-Update-on-Phase-1b-Positron-Emission-Tomography-PET-Trial-of-PIPE-791[8] Sangamo Therapeutics Announces Positive Topline Results From Registrational STAAR Study in Fabry Disease. Retrieved June 24, 2025 from https://www.businesswire.com/news/home/20250624043784/en/Sangamo-Therapeutics-Announces-Positive-Topline-Results-From-Registrational-STAAR-Study-in-Fabry-Disease[9] Immutep Announces Positive Update from Phase I Study of IMP761, a First-in-Class LAG-3 Agonist Antibody for Autoimmune Diseases. Retrieved June 24, 2025 from https://www.immutep.com/detail/immutep-announces-positive-update-from-phase-i-study-of-imp761-a-first-in-class-lag-3-agonist-antibody-for-autoimmune-diseases.html#:~:text=SYDNEY%2C%20AUSTRALIA%2C%20June%2023%2C%202025%20--%20Immutep%20Limited,a%20first-in-class%20LAG-3%20agonist%20antibody%20for%20autoimmune%20diseases.[10] Aclaris Therapeutics Initiates Phase 1a/1b Program for its Novel Bispecific Antibody ATI-052. Retrieved June 24, 2025 from https://www.globenewswire.com/news-release/2025/06/23/3103239/37216/en/index.html[11] Early data suggest Roche’s NXT007 may have the potential to provide haemostatic normalisation in people with haemophilia A. Retrieved June 24, 2025 from https://www.globenewswire.com/news-release/2025/06/23/3103084/0/en/Early-data-suggest-Roche-s-NXT007-may-have-the-potential-to-provide-haemostatic-normalisation-in-people-with-haemophilia-A.html[12] Verdiva Bio to Present New Data Highlighting Once-Weekly Potential of Its Investigational Oral Obesity Candidates at the ADA 85th Scientific Sessions. Retrieved June 24, 2025 from https://www.businesswire.com/news/home/20250620108098/en/Verdiva-Bio-to-Present-New-Data-Highlighting-Once-Weekly-Potential-of-Its-Investigational-Oral-Obesity-Candidates-at-the-ADA-85th-Scientific-Sessions[13] Plus Therapeutics Announces FDA Clearance of its Investigational New Drug Application using REYOBIQTM for the Treatment of Childhood Brain Cancer. Retrieved June 24, 2025 from https://www.globenewswire.com/news-release/2025/06/25/3104980/0/en/Plus-Therapeutics-Announces-FDA-Clearance-of-its-Investigational-New-Drug-Application-using-REYOBIQTM-for-the-Treatment-of-Childhood-Brain-Cancer.html[14] Assembly Biosciences Reports Positive Topline Results from Phase 1b Clinical Trial of Next-Generation Investigational Capsid Assembly Modulator ABI-4334 in Chronic Hepatitis B. Retrieved June 24, 2025 from https://www.globenewswire.com/news-release/2025/06/25/3105003/16259/en/Assembly-Biosciences-Reports-Positive-Topline-Results-from-Phase-1b-Clinical-Trial-of-Next-Generation-Investigational-Capsid-Assembly-Modulator-ABI-4334-in-Chronic-Hepatitis-B.html[15] Biogen to Advance Investigational Spinal Muscular Atrophy Asset to Registrational Studies Based on Positive Interim Phase 1 Results. Retrieved June 24, 2025 from https://www.globenewswire.com/news-release/2025/06/25/3104985/0/en/Biogen-to-Advance-Investigational-Spinal-Muscular-Atrophy-Asset-to-Registrational-Studies-Based-on-Positive-Interim-Phase-1-Results.html[16] Blue Earth Therapeutics: SNMMI Presentation of Results from Lutetium (177Lu) rhPSMA-10.1 Injection Phase 1 Clinical Trial. Retrieved June 24, 2025 from https://www.prnewswire.com/news-releases/blue-earth-therapeutics-snmmi-presentation-of-results-from-lutetium-177lu-rhpsma-10-1-injection-phase-1-clinical-trial-302490153.html[17] Metabolics Pharma Announces Positive Top-Line Results from Phase 1a Clinical Trial of ENT-03 in Obese and Diabetic Subjects. Retrieved June 24, 2025 from https://www.businesswire.com/news/home/20250625436712/en/Metabolics-Pharma-Announces-Positive-Top-Line-Results-from-Phase-1a-Clinical-Trial-of-ENT-03-in-Obese-and-Diabetic-Subjects[18] Aprea Reports Anti-Proliferative Results and Promising Early-Stage Clinical Data for Next-Generation WEE1 Inhibitor, APR-1051, in HPV+ Head and Neck Squamous Cell Carcinoma (HNSCC) in Collaboration with MD Anderson Cancer Center. Retrieved June 24, 2025 from https://www.globenewswire.com/news-release/2025/06/25/3105158/0/en/Aprea-Reports-Anti-Proliferative-Results-and-Promising-Early-Stage-Clinical-Data-for-Next-Generation-WEE1-Inhibitor-APR-1051-in-HPV-Head-and-Neck-Squamous-Cell-Carcinoma-HNSCC-in-C.html[19] CRISPR Therapeutics Reports Positive Additional Phase 1 Data for CTX310™ Targeting ANGPTL3 and Provides Update on In Vivo Cardiovascular Pipeline. Retrieved June 24, 2025 from https://www.globenewswire.com/news-release/2025/06/26/3105698/0/en/CRISPR-Therapeutics-Reports-Positive-Additional-Phase-1-Data-for-CTX310-Targeting-ANGPTL3-and-Provides-Update-on-In-Vivo-Cardiovascular-Pipeline.html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

Phase 1 clinical study of TERN-601 demonstrated differentiated profile in 28-day study; topline data were presented in September 2024 Phase 2 FALCON clinical trial of TERN-601 completed enrollment; 12-week data expected in 4Q 2025 FOSTER CITY, CA, USA I June 23, 2025 I Terns Pharmaceuticals, Inc. (“Terns” or the “Company”) (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology and obesity, today announced that data from the completed Phase 1 study of TERN-601, a novel once-daily oral GLP-1R agonist, will be highlighted at the American Diabetes Association (ADA) 85 th Scientific Sessions, taking place June 20-23, 2025, in Chicago, IL. “We are thrilled to be selected for an oral presentation at ADA to highlight additional data from the 28-day Phase 1 study of TERN-601 demonstrating its differentiated profile among oral GLP1-R agonists,” said Amy Burroughs, chief executive officer of Terns. “In addition, we are pleased to share the recent completion of enrollment for our Phase 2 FALCON trial where the key objectives of the trial are to demonstrate TERN-601’s competitive weight loss at 12-weeks, a class leading safety and tolerability profile, and the simplest dose titration amongst GLP-1R agonist therapies.” Topline data from the Phase 1 clinical study being presented at ADA were reported in September 2024 and provided the recommended doses taken forward in the ongoing Phase 2 FALCON study, which recently completed enrollment, with topline data expected in the fourth quarter of 2025. Key highlights from the ADA presentation include: The presentations and viewing detail are listed below: About the TERN-601 Phase 1 Trial The Phase 1 trial was a randomized, double-blind, placebo-controlled single and multiple-ascending dose (SAD and MAD) trial to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of TERN-601 in healthy adults with obesity or overweight. The trial consisted of two parts. Part 1 (SAD) was a single ascending dose study that evaluated five TERN-601 dose levels in healthy participants with a Body Mass Index (BMI) of ≥ 25 kg/m 2 and < 40 kg/m 2 . The starting TERN-601 dose was 30 mg, with subsequent dose levels based on review of emerging safety and PK data from prior cohorts. In Part 2 (MAD) of the trial, obese and overweight healthy adults were enrolled in cohorts that included titration of TERN-601 administered for 28 days at doses selected based on data from Part 1 (SAD). Part 2 included healthy participants with a BMI of ≥ 27 kg/m 2 to < 40 kg/m 2 . The primary endpoint of the trial was to evaluate safety and tolerability of TERN-601 administered once-daily for 28 days. Secondary endpoints included PK, efficacy as measured by body weight loss following 28 days of treatment with TERN-601, and other exploratory markers. About FALCON Phase 2 Trial FALCON is an ongoing U.S.-based, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of TERN-601, with once-daily dosing with or without food in adults with obesity or who are overweight, without diabetes (BMI ranges from ≥30 to <50 kg/m 2 or ≥27 to <30 kg/m 2 with at least one weight-related comorbidity). Patients are randomized to one of four active cohorts (n=30 per cohort): 250 mg, 500 mg, 500 mg slow titration, 750 mg or placebo. The primary endpoint is percent change from baseline in body weight compared to placebo over 12 weeks and secondary endpoints include safety, tolerability and proportion of patients achieving 5% weight loss or greater. About Terns Pharmaceuticals Terns Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology and obesity. Terns’ pipeline contains three clinical stage development programs including an allosteric BCR-ABL inhibitor, a small-molecule GLP-1 receptor agonist, a THR-β agonist, and a preclinical GIPR modulator discovery effort, prioritizing a GIPR antagonist nomination candidate. For more information, please visit: www.ternspharma.com . SOURCE: Terns Pharmaceuticals