一針起效，應答率達100%的多肽疫苗；使關鍵靶蛋白降解率超80%的口服小分子療法…… | 一周盤點

本期看點

1. 用于治療阿爾茨海默病的多肽疫苗ACI-35.030的1b/2a期臨床試驗結果積極，僅需1次注射即可讓所有受試者產生抗磷酸化Tau（pTau）IgG抗體滴度，2周時所有劑量組的應答率達100%。

2. 口服小分子IKZF1/3蛋白降解劑cemsidomide聯合地塞米松治療復發/難治性多發性骨髓瘤（RRMM）的1期臨床試驗數據積極，最高劑量組的總緩解率（ORR）達50%，關鍵靶蛋白IKZF1的降解率＞50%，IKZF3降解率＞80%。

ACI-35.030（JNJ-2056）：公布1b/2a期臨床試驗數據

AC Immune公司公布了其用于治療阿爾茨海默病的免疫療法ACI-35.030的1b/2a期臨床試驗結果。ACI-35.030基于AC Immune的SupraAntigen技術平臺開發，該技術將pTau肽錨定在脂質體中，同時包含非Tau T細胞表位和佐劑。試驗還研究了另一種免疫療法JACI-35.054，兩種療法針對同一靶點。

臨床數據顯示，針對同一靶點的兩種不同主動免疫療法制劑，能在早期阿爾茨海默病患者體內誘導產生有差異的抗體反應。安全性方面，ACI-35.030和JACI-35.054均未報告任何具有臨床意義的安全性或耐受性問題。ACI-35.030僅需一次注射即可使所有受試者產生抗pTau IgG抗體滴度，并在后續接種中持續提升抗體水平。在接受ACI-35.030治療后2周時，所有劑量組的所有受試者均被認定為抗pTau IgG應答者。在兩個高劑量組中，應答率在第74周時仍維持在94%至100%之間。目前，ACI-35.030已被選中推進至關鍵性2b期ReTain臨床試驗，用于治療臨床前期階段的阿爾茨海默病。

Cemsidomide：公布1期臨床試驗數據

C4 Therapeutics公司公布了其在研口服小分子IKZF1/3蛋白降解劑cemsidomide聯合地塞米松治療復發/難治性多發性骨髓瘤的1期臨床試驗數據。截至2025年7月23日的數據，在接受過多線治療的RRMM患者中，cemsidomide聯合地塞米松展現出強勁且持久的抗腫瘤活性。最高劑量組（100 μg）患者的ORR達50%；75 μg劑量組的ORR為40%。所有劑量組的中位緩解持續時間（DOR）為9.3個月，在兩個最高劑量組中，中位緩解持續時間尚未達到。

藥效學（PD）結果顯示，cemsidomide與地塞米松聯用可高效降解靶蛋白并激活T細胞，在人外周血單核細胞中，IKZF1的降解率＞50%、IKZF3降解率＞80%，且在所有劑量下均顯著增強T細胞活化和IL-2等細胞因子的產生，展現出與地塞米松聯用或與地塞米松+BCMA雙特異性T細胞銜接器（BCMA BiTE）聯用的潛力。安全性方面，沒有與cemsidomide相關的停藥事件，且很少有劑量減少事件（6%），為其在聯合治療方案中的廣泛應用提供了有力支持。

SYT-510：公布1期臨床試驗數據

Synendos Therapeutics公司公布了其核心候選藥物SYT-510在健康受試者中開展的1期臨床試驗的積極結果。SYT-510靶向內源性大麻素系統（ECS）中一個新近發現的靶點，屬于新型ECS調節劑——選擇性內源性大麻素再攝取抑制劑（SERIs）類別。

研究結果表明，SYT-510在所有劑量下均具有良好的耐受性，安全性良好。藥代動力學（PK）數據顯示，SYT-510能夠穿透血腦屏障，在中樞神經系統（CNS）中達到有效濃度。該藥物展現出明確的腦部藥效學作用，其對腦電圖（EEG）的影響與成功用于控制焦慮癥狀的抗焦慮藥物一致。

MF-300：公布1期臨床試驗數據

Epirium Bio公司宣布，其潛在“first-in-class”的口服15-羥基前列腺素脫氫酶（15-PGDH）抑制劑MF-300，在針對肌肉減少癥的1期臨床試驗中取得積極結果。5-PGDH是一種能將前列腺素E2（PGE2）轉化為非活性代謝物的酶。MF-300旨在可逆地結合到15-PGDH的PGE2結合位點上，阻止該酶轉化PGE2。在生化試驗中，MF-300能夠抑制15-PGDH的活性。在臨床前的細胞和動物研究中，MF-300可穩定和增加PGE2的水平。

此次試驗達到了主要安全性終點，所有研究劑量的MF-300總體耐受性良好，且無受試者因不良反應而退出。MF-300呈現出劑量依賴性的PD應答，該應答出現較早并隨時間的推移持續存在，而安慰劑組則未觀察到顯著變化，表明藥物成功與靶點結合并具有生物學活性。PK分析顯示，藥物暴露量隨劑量增加而上升，其半衰期支持每日一次口服給藥方案。

參考資料：

[1] Intellia Therapeutics Announces Positive Longer-Term Phase 1 Data for Nexiguran Ziclumeran (nex-z) in Patients with Hereditary Transthyretin (ATTR) Amyloidosis with Polyneuropathy. Retrieved September 26, 2025, from https://www.globenewswire.com/news-release/2025/09/25/3156402/0/en/Intellia-Therapeutics-Announces-Positive-Longer-Term-Phase-1-Data-for-Nexiguran-Ziclumeran-nex-z-in-Patients-with-Hereditary-Transthyretin-ATTR-Amyloidosis-with-Polyneuropathy.html

[2] Bambusa Therapeutics Announces Highly Positive Healthy Volunteer Results and First Atopic Dermatitis Patient Dosed in Phase I Trial of BBT001. Retrieved September 26, 2025, from https://www.prnewswire.com/news-releases/bambusa-therapeutics-announces-highly-positive-healthy-volunteer-results-and-first-atopic-dermatitis-patient-dosed-in-phase-i-trial-of-bbt001-302567230.html

[3] Rallybio Completes Dosing of First Cohort in RLYB116 Phase 1 Confirmatory Pharmacokinetic/Pharmacodynamic Study. Retrieved September 26, 2025, from https://www.businesswire.com/news/home/20250924016253/en/Rallybio-Completes-Dosing-of-First-Cohort-in-RLYB116-Phase-1-Confirmatory-PharmacokineticPharmacodynamic-Study

[4] uniQure Announces Positive Topline Results from Pivotal Phase I/II Study of AMT-130 in Patients with Huntington’s Disease. Retrieved September 26, 2025, from https://www.globenewswire.com/news-release/2025/09/24/3155348/0/en/uniQure-Announces-Positive-Topline-Results-from-Pivotal-Phase-I-II-Study-of-AMT-130-in-Patients-with-Huntington-s-Disease.html

[5] Kyverna Therapeutics Highlights Potential of KYV-101 in Multiple Sclerosis with Data from Phase 1 Investigator-Initiated Trials to be Presented at ECTRIMS. Retrieved September 26, 2025, from https://www.globenewswire.com/news-release/2025/09/24/3155539/0/en/Kyverna-Therapeutics-Highlights-Potential-of-KYV-101-in-Multiple-Sclerosis-with-Data-from-Phase-1-Investigator-Initiated-Trials-to-be-Presented-at-ECTRIMS.html

[6] Epirium Bio Announces Positive Phase 1 Clinical Trial Results Evaluating MF-300 in Healthy Volunteers, A First-In-Class, Oral 15-PGDH Enzyme Inhibitor, For the Treatment of Sarcopenia. Retrieved September 26, 2025, from https://www.businesswire.com/news/home/20250924461947/en/Epirium-Bio-Announces-Positive-Phase-1-Clinical-Trial-Results-Evaluating-MF-300-in-Healthy-Volunteers-A-First-In-Class-Oral-15-PGDH-Enzyme-Inhibitor-For-the-Treatment-of-Sarcopenia

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[11] Skye Presents Phase 1b Data for its Peripheral CB1-inhibiting Antibody, Nimacimab, at European Association for the Study of Diabetes (EASD) Annual Meeting. Retrieved September 26, 2025, from https://www.globenewswire.com/news-release/2025/09/19/3153078/0/en/Skye-Presents-Phase-1b-Data-for-its-Peripheral-CB1-inhibiting-Antibody-Nimacimab-at-European-Association-for-the-Study-of-Diabetes-EASD-Annual-Meeting.html

[12] C4 Therapeutics Presents Cemsidomide Phase 1 Multiple Myeloma Data Supporting Potential Best-in-Class Profile at the International Myeloma Society Annual Meeting. Retrieved September 26, 2025, from https://www.globenewswire.com/news-release/2025/09/20/3153507/0/en/C4-Therapeutics-Presents-Cemsidomide-Phase-1-Multiple-Myeloma-Data-Supporting-Potential-Best-in-Class-Profile-at-the-International-Myeloma-Society-Annual-Meeting.html

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[14] Peer-reviewed results from Phase 1b/2a Trial of Anti-pTau Active Immunotherapy from AC Immune Published in eBioMedicine. Retrieved September 26, 2025, from https://www.globenewswire.com/news-release/2025/09/25/3156158/0/en/Peer-reviewed-results-from-Phase-1b-2a-Trial-of-Anti-pTau-Active-Immunotherapy-from-AC-Immune-Published-in-eBioMedicine.html

免責聲明：本文僅作信息交流之目的，文中觀點不代表藥明康德立場，亦不代表藥明康德支持或反對文中觀點。本文也不是治療方案推薦。如需獲得治療方案指導，請前往正規醫院就診。

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