可穿越血腦屏障，創新NLRP3靶向小分子獲積極進展；三特異性NK細胞銜接器在美國遞交IND申請…… | 一周盤點

本期看點：

1. 具 良好 腦滲透性 的小分子NLRP 3抑制劑 BGE-102公布了 1期臨床試驗的新數據，給藥 14天后， 具有心血管風險因素的肥胖受試者的關鍵炎癥標志物水平下降86%，93%達到了正常水平。

2. GT Biopharma公司宣 布已向美國FDA提交了其新 型 B7-H3 靶向 三 特異性自然殺傷（NK）細胞銜接器 GTB-5550的IND申請。

BGE-102：公布1期臨床試驗的新數據

BioAge公司公布了其候選藥物BGE-102的1期臨床試驗的新數據。BGE-102是一種結構新穎、可口服的小分子NLRP3抑制劑，具有高活性及良好的腦滲透性，旨在用于治療具有心血管風險因素的患者。NLRP3是驅動與年齡相關炎癥的關鍵因子，與肥胖、神經退行性疾病及心血管疾病密切相關。該公司基于人類衰老隊列分析發現，NLRP3活性降低與長壽相關，因此將其確立為潛在治療靶點。BGE-102通過獨特的結合位點和機制抑制NLRP3炎性小體，作用方式區別于其他在研NLRP3抑制劑。

在一項針對肥胖（BMI 32–42）且基線高敏C反應蛋白（hsCRP）升高（>3 mg/L）的受試者開展的多劑量遞增（MAD）研究中，每日接受120 mg的BGE-102治療受試者的炎癥標志物顯示出迅速且顯著的減少。第14天時，受試者的中位hsCRP水平下降86%，93%（13/14）達到了正常水平（<2 mg/L）。此外，BGE-102還顯著降低了IL-6（系統性炎癥和心血管風險的關鍵驅動因子）和纖維蛋白原（心血管事件的獨立預測因子）水平。安全性方面，BGE-102的安全性和耐受性良好。

GTB-5550：向FDA提交IND申請

GT Biopharma公司宣布已向美國FDA提交了其新型候選藥物GTB-5550的IND申請。GTB-5550是一種靶向B7-H3的三特異性NK細胞銜接器，用于治療表達B7-H3抗原的實體腫瘤。該分子由三種組分組成，通過柔性接頭連接：1）靶向NK細胞表面CD16激活受體的納米體臂；2）野生型IL-15（WT IL-15）連接臂，用于促進NK細胞的增殖、活化和存活；3）靶向腫瘤細胞上B7-H3抗原的納米體臂，從而將NK細胞精準引導至腫瘤部位。

計劃開展的1期臨床試驗共分為兩個部分：1a期為劑量遞增階段，將評估最多7個劑量水平以確定最大耐受劑量（MTD）；1b期為劑量擴展階段，將在7種不同的轉移性癌癥隊列中（包括去勢抵抗性前列腺癌、卵巢癌、乳腺癌、頭頸癌、非小細胞肺癌、胰腺癌和膀胱癌）驗證1a期研究確定的MTD，并進一步評估藥物的耐受性。

ORKA-002：公布1期臨床試驗的中期數據

Oruka Therapeutics公司公布了其在研藥物ORKA-002在1期臨床試驗中取得積極的中期數據。ORKA-002旨在阻斷在銀屑病及其他炎癥性疾病發病機制中起關鍵作用的細胞因子，是一種靶向IL-17-A和IL-17-F的雙特異性抗體。

該1期研究是一項隨機、雙盲、安慰劑對照試驗，在24名健康成人受試者中評估了ORKA-002的安全性和藥代動力學特征。截至2026年1月數據截止日期的結果，ORKA-002的半衰期達75–80天，支持銀屑病患者實現每年兩次的給藥頻率，以及化膿性汗腺炎（HS）患者每季度一次的給藥頻率。藥效學分析顯示，在體外IL-17刺激實驗中，所有劑量組均能強效抑制IL-17信號傳導，效果持續至末次隨訪（最長24周），進一步支持兩年一次給藥的潛力。安全性方面，ORKA-002在所有劑量水平下均耐受良好，安全性與抗IL-17類藥物一致。ORKA-002的2期研究預計將于2026年1月啟動，針對銀屑病，下半年將啟動針對化膿性汗腺炎的研究。

參考資料：

[1] Benitec Biopharma Provides Positive Long-Term Clinical Study Results for BB-301 Phase 1b/2a Clinical Trial Demonstrating Robust Efficacy and Continued Durability of Response. Retrieved January 16, 2026, from https://www.globenewswire.com/news-release/2026/01/11/3216469/0/en/Benitec-Biopharma-Provides-Positive-Long-Term-Clinical-Study-Results-for-BB-301-Phase-1b-2a-Clinical-Trial-Demonstrating-Robust-Efficacy-and-Continued-Durability-of-Response.html

[2] Ocugen Announces Publication of Phase 1 GARDian1 Trial Results for OCU410ST Modifier Gene Therapy. Retrieved January 16, 2026, from https://www.globenewswire.com/news-release/2026/01/12/3216661/0/en/Ocugen-Announces-Publication-of-Phase-1-GARDian1-Trial-Results-for-OCU410ST-Modifier-Gene-Therapy.html

[3] Tessera Therapeutics Announces FDA Clearance of IND Application for its Lead In Vivo Gene Editing Program TSRA-196 for AATD. Retrieved January 16, 2026, from https://www.globenewswire.com/news-release/2026/01/12/3216718/0/en/Tessera-Therapeutics-Announces-FDA-Clearance-of-IND-Application-for-its-Lead-In-Vivo-Gene-Editing-Program-TSRA-196-for-AATD.html

[4] Oruka Therapeutics Announces Positive Interim Phase 1 Data for ORKA-002 and Initiation of EVERLAST-B Trial of ORKA-001. Retrieved January 16, 2026, from https://www.globenewswire.com/news-release/2026/01/12/3216715/0/en/Oruka-Therapeutics-Announces-Positive-Interim-Phase-1-Data-for-ORKA-002-and-Initiation-of-EVERLAST-B-Trial-of-ORKA-001.html

[5] Lexeo Therapeutics Announces Positive Interim Phase I/II Data for LX2020 for the Treatment of PKP2-Associated Arrhythmogenic Cardiomyopathy. Retrieved January 16, 2026, from https://www.globenewswire.com/news-release/2026/01/12/3216688/0/en/Lexeo-Therapeutics-Announces-Positive-Interim-Phase-I-II-Data-for-LX2020-for-the-Treatment-of-PKP2-Associated-Arrhythmogenic-Cardiomyopathy.html

[6] Solid Biosciences Doses First Participant in First-in-Class Phase 1b FALCON Trial Evaluating SGT-212 Dual-Route Gene Therapy for the Treatment of Friedreich’s Ataxia. Retrieved January 16, 2026, from https://www.globenewswire.com/news-release/2026/01/12/3216871/0/en/Solid-Biosciences-Doses-First-Participant-in-First-in-Class-Phase-1b-FALCON-Trial-Evaluating-SGT-212-Dual-Route-Gene-Therapy-for-the-Treatment-of-Friedreich-s-Ataxia.html

[7] Recludix Pharma Announces Dosing of First Subjects in a Phase 1 Study of REX-8756, a Potent and Selective Oral STAT6 Inhibitor, and Achieves Associated $20 Million Milestone Payment Under Collaboration with Sanofi. Retrieved January 16, 2026, from https://www.globenewswire.com/news-release/2026/01/12/3216802/0/en/Recludix-https://www.mareatx.com/press-releases/marea-therapeutics-unveils-positive-topline-phase-1-data-for-mar002-in-acromegaly-demonstrates-potential-for-best-in-disease-efficacy-and-dosing-profile/Pharma-Announces-Dosing-of-First-Subjects-in-a-Phase-1-Study-of-REX-8756-a-Potent-and-Selective-Oral-STAT6-Inhibitor-and-Achieves-Associated-20-Million-Milestone-Payment-U.html

[8] BioAge Announces Additional Positive Interim Phase 1 Data for BGE-102, a Novel Brain-Penetrant NLRP3 Inhibitor, Demonstrating Potential for Best-in-Class hsCRP Reduction in Participants with Elevated Cardiovascular Risk. Retrieved January 16, 2026, from https://www.globenewswire.com/news-release/2026/01/12/3216965/0/en/BioAge-Announces-Additional-Positive-Interim-Phase-1-Data-for-BGE-102-a-Novel-Brain-Penetrant-NLRP3-Inhibitor-Demonstrating-Potential-for-Best-in-Class-hsCRP-Reduction-in-Participa.html

[9] Curasight Announces Encouraging Preliminary Data from Phase 1 Trial Evaluating First-in-Class Radiopharmaceutical uTREAT in High-Grade Gliomas?. Retrieved January 16, 2026, from https://www.prnewswire.com/news-releases/curasight-announces-encouraging-preliminary-data-from-phase-1-trial-evaluating-first-in-class-radiopharmaceutical-utreat-in-high-grade-gliomas-302658795.html

[10] Marea Therapeutics Unveils Positive Topline Phase 1 Data for MAR002 in Acromegaly; Demonstrates Potential for Best-in-Disease Efficacy and Dosing Profile. Retrieved January 16, 2026, from https://www.mareatx.com/press-releases/marea-therapeutics-unveils-positive-topline-phase-1-data-for-mar002-in-acromegaly-demonstrates-potential-for-best-in-disease-efficacy-and-dosing-profile/

[11] Marea Therapeutics Unveils Positive Topline Phase 1 Data for MAR002 in Acromegaly; Demonstrates Potential for Best-in-Disease Efficacy and Dosing Profile. Retrieved January 16, 2026, from https://www.mareatx.com/press-releases/marea-therapeutics-unveils-positive-topline-phase-1-data-for-mar002-in-acromegaly-demonstrates-potential-for-best-in-disease-efficacy-and-dosing-profile/

[12] GT Biopharma Announces IND Submission for GTB-5550 TriKE?, a B7-H3-targeted natural killer (NK) cell engager for B7-H3 expressing solid tumor cancers. Retrieved January 16, 2026, from https://www.globenewswire.com/news-release/2026/01/15/3219554/0/en/GT-Biopharma-Announces-IND-Submission-for-GTB-5550-TriKE-a-B7-H3-targeted-natural-killer-NK-cell-engager-for-B7-H3-expressing-solid-tumor-cancers.html

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