▎藥明康德

本期看點

1. ROS1選擇性抑制劑zidesamtinib用于 接受過酪氨酸激酶抑制劑（TKI）治療 的晚期ROS1陽性非小 細胞肺癌（NSCLC）患者，在一項1/2期臨床試驗中取得積極結果，其 上市申請遞交在即 。

2. 早期數據表明，羅氏（Roche）的在研雙特異性抗體NXT007有望使血友病A患者的凝血功能恢復正常。

3. 用于治療慢性乙型肝炎病毒（HBV）感染的下一代衣殼組裝調節劑ABI-4334在1b期臨床試驗中展現強力的抗病毒活性，高劑量組患者接受治療28天，血漿HBV DNA平均降低3.2 log IU/mL。

NXT007：公布1/2期臨床試驗數據

羅氏宣布，其新一代在研雙特異性抗體NXT007在治療血友病A的1/2期臨床試驗中取得積極數據，將推進至3期臨床試驗。NXT007由羅氏旗下的Chugai Pharmaceutical公司研發，基于已上市藥物Hemlibra的框架優化設計，旨在模擬因子VIII功能，同時延長半衰期，提高療效和用藥便利性。該藥通過將凝血因子IXa和X橋接在一起，激活體內自然凝血級聯反應，有望使血友病A患者的凝血功能恢復正常，并減少治療負擔。

在這項研究中，30名12至65歲、無因子VIII抑制劑，且既往未接受過Hemlibra治療的血友病A患者在接受了4至6周的負荷劑量后，在維持期每2至4周皮下注射遞增劑量的NXT007。結果顯示，高劑量組（B-3和B-4）的患者在整個維持期內均保持止血正常化狀態，未出現需治療的出血事件。安全性方面，NXT007的耐受良好，目前未報告血栓栓塞事件。

Zidesamtinib：公布1/2期臨床試驗數據

Nuvalent公司公布了其新型ROS1選擇性抑制劑zidesamtinib在1/2期臨床試驗ARROS-1中的關鍵積極數據。該試驗針對接受過TKI治療的晚期ROS1陽性NSCLC患者。Zidesamtinib是一種具腦滲透性的ROS1抑制劑，設計用以治療那些對現有ROS1抑制劑具抗性的癌癥，包含那些帶有G2032R、S1986Y/F、L2026M或D2033N突變的腫瘤。

結果顯示，在117例曾接受過TKI治療的ROS1陽性NSCLC患者中（其中50%曾接受過≥2種ROS1 TKI±化療），由盲態獨立中心審查（BICR）評估的客觀緩解率（ORR）為44%，初步估計的緩解持續率在12個月時為78%，18個月時為62%。在其中55名曾接受過1種ROS1 TKI（克唑替尼或恩曲替尼）±化療的患者中，ORR為51%，初步估計的緩解持續率在12和18個月時均為93%。Zidesamtinib還顯示出顱內抗腫瘤活性，對攜帶ROS1G2032R耐藥突變的腫瘤也有作用，整體安全性良好，劑量減少和停藥的比例較低，分別為10%和2%。該公司計劃于2025年7月啟動滾動提交zidesamtinib的新藥申請（NDA），目標在2025年第三季度完成。

ABI-4334：公布1b期臨床試驗數據

Assembly Biosciences公司公布了其在研下一代衣殼組裝調節劑ABI-4334用于治療慢性HBV感染患者的1b期臨床試驗數據。此前公布的150 mg劑量組的結果顯示，ABI-4334顯示出很強的抗病毒活性，在28天的治療中，血漿HBV DNA平均降低了2.9 log IU/mL。此次公布的400 mg劑量組的結果類似于先前的報道，在28天的治療中，血漿HBV DNA平均降低了3.2 log IU/mL。此外，在400 mg劑量下繼續觀察到ABI-4334良好的安全性和耐受性，半衰期支持每日一次口服給藥。

TERN-601：公布1期臨床試驗數據

Terns Pharmaceuticals公司公布了其每日一次在研減重療法TERN-601在肥胖或超重健康成年人中進行的1期試驗積極結果。TERN-601是一種口服小分子胰高血糖素樣肽-1（GLP-1）受體激動劑，由Terns內部研發。TERN-601通過Terns內部基于結構的藥物研發技術設計，采用該公司專有的三維定量構效關系（QSAR）模型所開發。

此次公布的結果顯示，TERN-601在治療肥胖方面表現出顯著的療效和良好的安全性。在28天內，每日一次給藥可實現統計學顯著且呈劑量依賴性的體重減輕。在最高劑量組中，有67%的患者體重減輕≥5%。其獨特的藥代動力學特性使其在24小時內維持平穩的血藥濃度曲線，有效半衰期為9-10小時，支持每日一次給藥。此外，藥物在腸道中的暴露量高于血漿，且游離藥物比例低，從而在不犧牲耐受性的前提下實現了有意義的體重減輕。安全性方面，未出現因治療導致的中斷、減量或停藥，＞95%的胃腸道不良事件為輕度，患者的肝酶、生命體征和心電圖均無明顯變化。

ENT-03：公布1a期臨床試驗數據

Metabolics Pharma公司公布了其候選藥物ENT-03在肥胖和糖尿病患者中開展的1a期臨床試驗的的初步結果。該研究數據顯示，在所有測試劑量下，ENT-03均表現出良好的安全性和耐受性。在較高劑量組中，ENT-03在減輕體重和提高胰島素敏感性方面呈現出積極趨勢。

ENT-03是一種新型中樞神經系統作用的氨基類固醇化合物，具有蛋白酪氨酸磷酸酶1B（PTP1B）抑制活性。它通過作用于大腦中調控能量代謝和血糖平衡的神經回路，達到調節葡萄糖水平、改善胰島素敏感性并促進體重減輕的效果。臨床前研究表明，ENT-03作為單藥療法有效，并且在與GLP-1受體激動劑聯合使用時表現出累加效應。此外，ENT-03在停藥后仍可維持較長時間的體重降低以及血糖和胰島素水平的正常化。

APR-1051：公布聯合治療1期試驗的初步數據

Aprea Therapeutics公司公布了其下一代口服WEE1抑制劑APR-1051治療HPV陽性頭頸部鱗狀細胞癌患者的新臨床數據。APR-1051是一種口服、高選擇性的WEE1抑制劑，旨在最大限度地減少脫靶活性并優化藥理選擇性。該療法目前正在1期臨床試驗ACESOT-1051中對攜帶DDR相關通路基因突變（DDR）的晚期實體瘤患者進行評估。

該試驗中，一名62歲HPV陽性的晚期口咽鱗狀細胞癌男性患者，既往接受過三線鉑類治療后進展，在接受每日口服一次70 mg亞治療劑量的APR-1051后實現疾病穩定，首次影像學評估時腫瘤縮小了5%。該患者對治療的耐受性良好，未報告劑量限制性毒性。

參考資料（可上下滑動查看）

[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

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