每周一次，使病變發生率降低94%的抗病毒療法；穿越血腦屏障的變構小分子療法早期結果積極…… | 一周盤點

本期看點

1. Assembly Biosciences公司公布了用于治療復發性生殖器皰疹的抗病毒療法ABI-5366的積極早期臨床研究數據，每周給藥一次，患者的生殖器病變率下降94%。

2. 治療帕金森病的變構小分子療法GT-02287的早期臨床結果積極，首批9名受試者已觀察到運動障礙協會-統一帕金森病評定量表（MDS-UPDRS）的改善。

ABI-5366：公布1b期臨床試驗的中期數據

Assembly Biosciences公司公布了一種用于治療復發性生殖器皰疹的長效解旋酶-引物酶抑制劑ABI-5366的1b期臨床試驗數據。該候選療法通過靶向病毒解旋酶-引物酶復合體發揮作用。這是一種在HSV-1和HSV-2中都保守的重要病毒酶復合體，并且宿主細胞中沒有類似的酶復合體。在短期臨床研究中，HSV解旋酶-引物酶抑制劑顯示出比核苷類似物更佳的療效潛力。

此次公布的結果顯示，在接受每周一次350 mg ABI-5366口服劑量的隊列中，與安慰劑組相比，患者的HSV-2病毒脫落率、高病毒載量脫落率和生殖器病變率均出現具有統計學意義的顯著下降，降幅分別達到94%、98%和94%。藥代動力學特征支持ABI-5366采用每周甚至有望每月一次的給藥方案。

GT-02287：公布1b期臨床試驗的初步數據

Gain Therapeutics公布了其用于治療帕金森病的在研變構小分子GT-02287的1b期試驗的初步數據。GT-02287是一種口服變構蛋白調節劑，具有可穿越血腦屏障的能力。該藥物可恢復溶酶體蛋白酶葡萄糖腦苷脂酶（GCase）的功能，該酶由于

GBA1

在帕金森病的臨床前模型中，GT-02287恢復了GCase酶功能，減少了聚集的α突觸核蛋白、神經炎癥和神經元死亡，提高了多巴胺水平，改善動物的運動功能和認知能力，可能具有減緩帕金森病進展的潛力。此外，GT-02287顯著降低了血漿神經絲輕鏈（NfL）水平，這是一種神經退行性疾病的生物標志物。

此次公布的結果顯示，GT-02287總體耐受性良好，未發生任何治療伴發嚴重不良事件。首批9名受試者已觀察到MDS-UPDRS的改善，其余受試者的90天隨訪仍在進行中。患者的血漿藥物暴露水平處于預期的治療范圍內，且與此前1期健康受試者研究中的暴露水平相當。

Zeleciment basivarsen（DYNE-101）：公布1/2期臨床試驗的新數據

Dyne Therapeutics公司公布了在研抗體偶聯反義寡核苷酸療法zeleciment basivarsen，在治療強直性肌營養不良1型（DM1）患者的1/2期臨床試驗ACHIEVE中的新數據。DYNE-101由與抗體片段（Fab）偶聯的反義寡核苷酸組成，Fab與肌肉上高表達的轉鐵蛋白受體1（TfR1）結合。它旨在實現靶向肌肉組織遞送，目的是減少細胞核中的有毒DMPK基因的RNA，允許正常mRNA處理和正常蛋白翻譯，并有可能阻止或逆轉疾病進展。DYNE-101已被歐洲藥品管理局（EMA）和美國FDA授予孤兒藥資格，用于治療DM1。

此次公布的結果顯示，zeleciment basivarsen為患者提供了廣泛的功能改善。通過視頻手部張開時間（vHOT）測試顯示，患者手部肌強直相對于基線有顯著且持續的改善。在多個功能終點上觀察到相對于基線有意義且持續的改善，包括10米步行/跑步測試（10MWR）和5次坐站測試（5xSTS）的結果，以及用于衡量上肢功能的9孔釘測試（9HPT）結果的改善。定量肌力測試（QMT）顯示上下肢多個肌群肌力均得到改善，測試項目包括握力、屈肘、伸肘、踝背屈、屈膝、伸膝。患者報告的強直性營養不良健康指數（MDHI）結果顯示在認知障礙、睡眠障礙、疲勞、溝通、情緒問題、疼痛及活動能力等多個指標上，相對于基線有有意義且持續的改善。此外，患者和臨床醫生對整體功能的印象相對于基線有所改善。安全性方面，該藥物安全性良好，未發現嚴重治療伴發不良事件。

參考資料：

[1] Ovid announces positive topline results for the next-generation GABA-aminotransferase inhibitor, OV329, that demonstrate strong inhibitory activity and a potential best-in-category safety profile. Retrieved October 10, 2025, from https://investors.ovidrx.com/news/news-details/2025/Ovid-announces-positive-topline-results-for-the-next-generation-GABA-aminotransferase-inhibitor-OV329-that-demonstrate-strong-inhibitory-activity-and-a-potential-best-in-category-safety-profile/default.aspx

[2] Taysha Gene Therapies Presents New Supplemental Data Analysis from Part A of the REVEAL Phase 1/2 Trials for TSHA-102 in Rett Syndrome at the 54th CNS Annual Meeting. Retrieved October 10, 2025, from https://www.globenewswire.com/news-release/2025/10/09/3164079/0/en/Taysha-Gene-Therapies-Presents-New-Supplemental-Data-Analysis-from-Part-A-of-the-REVEAL-Phase-1-2-Trials-for-TSHA-102-in-Rett-Syndrome-at-the-54th-CNS-Annual-Meeting.html

[3] Complement Therapeutics Receives FDA IND Clearance to Advance CTx001 into Opti-GAIN, a Phase I/II Clinical Trial in Geographic Atrophy secondary to AMD. Retrieved October 10, 2025, from https://www.prnewswire.com/news-releases/complement-therapeutics-receives-fda-ind-clearance-to-advance-ctx001-into-opti-gain-a-phase-iii-clinical-trial-in-geographic-atrophy-secondary-to-amd-302577045.html

[4] Arvinas Presents Late Breaking, Positive Phase 1 Clinical Data for ARV-102, a PROTAC LRRK2 Degrader, at the 2025 International Congress of Parkinson’s Disease and Movement Disorders?. Retrieved October 10, 2025, from https://www.globenewswire.com/news-release/2025/10/05/3161349/0/en/Arvinas-Presents-Late-Breaking-Positive-Phase-1-Clinical-Data-for-ARV-102-a-PROTAC-LRRK2-Degrader-at-the-2025-International-Congress-of-Parkinson-s-Disease-and-Movement-Disorders.html

[5] Herantis Pharma presents positive topline data for HER-096 in Phase 1b trial for people living with Parkinson’s disease. Retrieved October 10, 2025, from https://www.globenewswire.com/news-release/2025/10/07/3162855/0/en/Herantis-Pharma-presents-positive-topline-data-for-HER-096-in-Phase-1b-trial-for-people-living-with-Parkinson-s-disease.html

[6] Adicet Bio Announces Positive Preliminary Data from ADI-001 Phase 1 Study in Patients with Lupus Nephritis (LN) and Systemic Lupus Erythematosus (SLE). Retrieved October 10, 2025 from https://www.businesswire.com/news/home/20251006091236/en/Adicet-Bio-Announces-Positive-Preliminary-Data-from-ADI-001-Phase-1-Study-in-Patients-with-Lupus-Nephritis-LN-and-Systemic-Lupus-Erythematosus-SLE

[7] BlueRock Therapeutics reports positive 36-month results from Phase I trial of bemdaneprocel for treating Parkinson’s disease. Retrieved October 10, 2025 from https://www.bluerocktx.com/bluerock-therapeutics-reports-positive-36-month-results-from-phase-i-trial-of-bemdaneprocel-for-treating-parkinsons-disease/

[8] Gain Therapeutics Presents Initial Data from Phase 1b Clinical Study of GT-02287 in Parkinson’s Patients at International Congress of Parkinson’s Disease and Movement Disorders?. Retrieved October 10, 2025 from https://gaintherapeutics.com/newsroom/press-releases/press-releases-2025/gain-therapeutics-presents-initial-data-from-phase-1b-clinical-study-of-gt-02287-in-parkinsons-patients-at-international-congress-of-parkinsons-disease-and-movement-disorders/

[9] Spur Therapeutics Presents Updated Phase 1/2 Data on Its Gene Therapy Candidate in Gaucher Disease at ESGCT 32nd Annual Congress. Retrieved October 10, 2025 from https://www.globenewswire.com/news-release/2025/10/07/3162226/0/en/Spur-Therapeutics-Presents-Updated-Phase-1-2-Data-on-Its-Gene-Therapy-Candidate-in-Gaucher-Disease-at-ESGCT-32nd-Annual-Congress.html

[10] Dyne Therapeutics Announces Additional One-Year Clinical Data Demonstrating Functional Improvement from Phase 1/2 ACHIEVE Trial of Zeleciment Basivarsen (DYNE-101) for Myotonic Dystrophy Type 1 (DM1). Retrieved October 10, 2025 from https://www.globenewswire.com/news-release/2025/10/06/3162171/0/en/Dyne-Therapeutics-Announces-Additional-One-Year-Clinical-Data-Demonstrating-Functional-Improvement-from-Phase-1-2-ACHIEVE-Trial-of-Zeleciment-Basivarsen-DYNE-101-for-Myotonic-Dystr.html

[11] Cabaletta Bio Presents First Rese-cel Data with No Preconditioning Demonstrating Biologic Activity and Early Clinical Responses at the 2025 ESGCT Annual Congress. Retrieved October 10, 2025 from https://www.cabalettabio.com/investors/news-events/press-releases/detail/135/cabaletta-bio-presents-first-rese-cel-data-with-no

[12] AskBio Presents Interim Safety Results from Phase 1/Phase 2 LION-CS101 Clinical Trial of AB-1003 in Participants with Limb-Girdle Muscular Dystrophy 2I/R9. Retrieved October 10, 2025 from https://www.globenewswire.com/news-release/2025/10/10/3164826/0/en/AskBio-Presents-Interim-Safety-Results-from-Phase-1-Phase-2-LION-CS101-Clinical-Trial-of-AB-1003-in-Participants-with-Limb-Girdle-Muscular-Dystrophy-2I-R9.html

[13] Assembly Biosciences Presents Interim Phase 1b Data for HSV Helicase-Primase Inhibitor Candidate ABI-5366 at the 38th Congress of the International Union Against Sexually Transmitted Infections (IUSTI)- Europe. Retrieved October 10, 2025 from https://www.globenewswire.com/news-release/2025/10/10/3164831/16259/en/Assembly-Biosciences-Presents-Interim-Phase-1b-Data-for-HSV-Helicase-Primase-Inhibitor-Candidate-ABI-5366-at-the-38th-Congress-of-the-International-Union-Against-Sexually-Transmitt.html

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