本期看點

1. 用于治療腎病的 在研藥物povetacicept在早期臨床研究中表 現(xiàn)亮眼， 48周數(shù)據(jù)顯示，IgA腎病 （IgAN）患者 中蛋白尿較基線下降64%， 原發(fā)性膜性腎病 （pMN）患者的 蛋白尿較基線下降82%， 且兩種疾病的 估算腎小球濾過率（eGFR） 均保持 穩(wěn)定。

2. α/β-IL-2受體偏向性部分激動劑 STK-01 2與標(biāo)準(zhǔn)治療方案聯(lián)用，一線治療PD-L1陰性非鱗狀非小細胞肺癌（NSCLC）患者的早期臨床試驗數(shù)據(jù)積極， PD-L1陰性患者的客觀緩解率（ORR）為53%，與標(biāo)準(zhǔn)治療方案23-32%的歷史緩解率相比具有優(yōu)勢。

Povetacicept：公布1/2期臨床試驗的新數(shù)據(jù)

Vertex Pharmaceuticals公司公布了其在研藥物povetacicept（pove）在IgA腎病和原發(fā)性膜性腎病中的48周最新數(shù)據(jù)。Povetacicept是一種高效BAFF（B細胞激活因子）和APRIL（一種增殖誘導(dǎo)配體）的雙重拮抗劑，是一款經(jīng)改造TACI結(jié)構(gòu)域變體的Fc融合體。BAFF與APRIL細胞因子因其在B細胞（特別是抗體分泌細胞）、T細胞和先天免疫細胞中的激活、分化和/或生存所扮演的角色，在多種自身免疫性疾病的發(fā)病機制中發(fā)揮關(guān)鍵作用。憑借其工程化的TACI結(jié)構(gòu)域，pove在臨床前研究中展現(xiàn)出優(yōu)于其他同類抑制劑的結(jié)合親和力、效力和組織穿透能力。目前，該藥已獲美國FDA授予pMN適應(yīng)癥的快速通道資格，并計劃啟動生物制品許可申請的滾動提交以爭取加速批準(zhǔn)。

在IgAN患者中（n=21），接受每4周一次80 mg劑量pove皮下給藥48周后，平均24小時尿蛋白肌酐比（UPCR）較基線下降64%，eGFR保持穩(wěn)定，90%的患者實現(xiàn)血尿緩解，53%達到臨床緩解（定義為UPCR<0.5 g/g、血尿陰性且eGFR較基線降低<25%）。在pMN患者中（n=10），平均24小時UPCR降幅達82%，eGFR同樣穩(wěn)定，40%患者實現(xiàn)完全臨床緩解（UPCR<0.5 g/g）。Pove總體安全性和耐受性良好，不良事件多為輕中度，沒有發(fā)生嚴(yán)重不良事件，安全性特征在兩個疾病隊列中相似。

STK-012：公布1a/1b期聯(lián)合治療試驗的初步數(shù)據(jù)

Synthekine公司公布了其在研藥物STK-012與標(biāo)準(zhǔn)治療方案（pembrolizumab聯(lián)合化療）聯(lián)用，一線治療PD-L1陰性非鱗狀非小細胞肺癌患者的早期臨床試驗數(shù)據(jù)。STK-012是一種潛在“first-in-class”的α/β-IL-2受體偏向性部分激動劑，旨在選擇性激活抗原特異性T細胞以增強抗腫瘤免疫反應(yīng)，并避免對其他淋巴細胞的廣泛刺激，例如與IL-2毒性相關(guān)的自然殺傷（NK）細胞。

此次公布的結(jié)果顯示，STK-012聯(lián)合療法顯示出良好的安全性和有效性，無明顯IL-2毒性。在25名安全性可評估的受試者中，最常見的治療相關(guān)不良事件（TRAE）是可控制且可逆的惡心、疲勞和皮疹/皮炎。沒有受試者因TRAE而停止STK-012治療。在21例療效可評估的患者中，STK-012聯(lián)合標(biāo)準(zhǔn)治療展現(xiàn)出優(yōu)于歷史對照的抗腫瘤活性：PD-L1<1%患者的整體ORR達53%，遠高于既往PD-L1陰性患者接受標(biāo)準(zhǔn)治療方案23–32%的緩解率。值得注意的是，在10例攜帶

STK11

KEAP1

SMARCA4

APG333：公布1期臨床試驗的中期數(shù)據(jù)

Apogee Therapeutics公司公布了其在研藥物APG333的首次人體1期試驗的中期數(shù)據(jù)。APG333是一種具有延長半衰期的新型單克隆抗體，靶向一種上皮細胞來源的細胞因子TSLP，該細胞因子在促進免疫細胞募集和激活方面發(fā)揮著重要作用，已被臨床驗證為治療哮喘等炎癥性疾病的有效靶點。

此次公布的數(shù)據(jù)顯示，APG333在所有隊列中均耐受性良好，劑量高達1000 mg。APG333的半衰期約為55天，單次給藥后可持續(xù)抑制關(guān)鍵炎癥生物標(biāo)志物長達6個月，顯著超出試驗預(yù)設(shè)目標(biāo)，有望支持每3個月或6個月一次的給藥方案。此外，由于TSLP抑制劑可與其他單抗聯(lián)用以擴大療效人群，Apogee公司計劃將APG333與其另一候選藥物APG777聯(lián)合開發(fā)為復(fù)方制劑（APG273），用于呼吸道疾病，目標(biāo)實現(xiàn)每季度一次甚至更少頻次的給藥。

參考資料：

[1] Vertex Presents Updated Phase 1/2 Data From RUBY-3 Study That Continue to Demonstrate Best-in-Class Potential for Povetacicept in Adults with IgA Nephropathy and Primary Membranous Nephropathy at American Society of Nephrology Kidney Week. Retrieved November 14, 2025, from https://news.vrtx.com/news-releases/news-release-details/vertex-presents-updated-phase-12-data-ruby-3-study-continue

[2] CRISPR Therapeutics Announces Positive Phase 1 Clinical Data for CTX310? Demonstrating Deep and Durable ANGPTL3 Editing, Triglyceride and Lipid Lowering. Retrieved November 14, 2025, from https://www.globenewswire.com/news-release/2025/11/08/3184062/0/en/CRISPR-Therapeutics-Announces-Positive-Phase-1-Clinical-Data-for-CTX310-Demonstrating-Deep-and-Durable-ANGPTL3-Editing-Triglyceride-and-Lipid-Lowering.html

[3] Tenaya Therapeutics Presents Promising Interim Clinical Data from MYPEAK?-1 Phase 1b/2a Clinical Trial of TN-201 Gene Therapy for the Treatment of MYBPC3-Associated Hypertrophic Cardiomyopathy. Retrieved November 14, 2025, from https://www.globenewswire.com/news-release/2025/11/08/3184075/0/en/Tenaya-Therapeutics-Presents-Promising-Interim-Clinical-Data-from-MYPEAK-1-Phase-1b-2a-Clinical-Trial-of-TN-201-Gene-Therapy-for-the-Treatment-of-MYBPC3-Associated-Hypertrophic-Car.html

[4] Intellia Therapeutics Presents Positive Pooled Phase 1/2 Data of Lonvoguran Ziclumeran (lonvo-z) in Patients with Hereditary Angioedema. Retrieved November 14, 2025, from https://www.globenewswire.com/news-release/2025/11/08/3184092/0/en/Intellia-Therapeutics-Presents-Positive-Pooled-Phase-1-2-Data-of-Lonvoguran-Ziclumeran-lonvo-z-in-Patients-with-Hereditary-Angioedema.html

[5] Intellia Therapeutics Presents Positive Longer-Term Phase 1 Data of Nexiguran Ziclumeran (nex-z) in Patients with Transthyretin (ATTR) Amyloidosis with Cardiomyopathy. Retrieved November 14, 2025, from https://www.globenewswire.com/news-release/2025/11/10/3184975/0/en/Intellia-Therapeutics-Presents-Positive-Longer-Term-Phase-1-Data-of-Nexiguran-Ziclumeran-nex-z-in-Patients-with-Transthyretin-ATTR-Amyloidosis-with-Cardiomyopathy.html

[6] Vittoria Biotherapeutics Announces Presentation of First-in-Human Interim Phase1 Data for VIPER-101 at ASH2025. Retrieved November 14, 2025, from https://www.globenewswire.com/news-release/2025/11/10/3184573/0/en/Vittoria-Biotherapeutics-Announces-Presentation-of-First-in-Human-Interim-Phase1-Data-for-VIPER-101-at-ASH2025.html

[7] Apogee Therapeutics Announces Positive Interim Phase 1 Results from Healthy Volunteer Trial of APG333, its Novel Half-Life Extended TSLP Antibody. Retrieved November 14, 2025, from https://www.globenewswire.com/news-release/2025/11/10/3184340/0/en/Apogee-Therapeutics-Announces-Positive-Interim-Phase-1-Results-from-Healthy-Volunteer-Trial-of-APG333-its-Novel-Half-Life-Extended-TSLP-Antibody.html

[8] A2 Biotherapeutics Presents Initial Safety and Efficacy Data from Ongoing Phase 1/2 EVEREST-2 Study, Including First Report of a Complete Response to CAR T-Cell Therapy in a Patient with NSCLC. Retrieved November 14, 2025, from https://www.a2bio.com/a2-biotherapeutics-presents-initial-safety-and-efficacy-data-from-ongoing-phase-1-2-everest-2-study-including-first-report-of-a-complete-response-to-car-t-cell-therapy-in-a-patient-with-nsclc/

[9] Synthekine Presents Positive Initial Results from Phase 1a/1b Clinical Trial of STK-012 Plus Pembrolizumab and Chemotherapy in First-Line, PD-L1 Negative Nonsquamous Non-Small Cell Lung Cancer. Retrieved November 14, 2025, from https://www.synthekine.com/news/synthekine-presents-positive-initial-results-from-phase-1a-1b-clinical-trial-of-stk-012-plus-pembrolizumab-and-chemotherapy-in-first-line-pd-l1-negative-nonsquamous-non-small-cell-lung-cancer/

[10] Remedy Plan Therapeutics Advances RPT1G for Myeloid Cancer Patients with Phase 1 Safety Data and IND Approval. Retrieved November 14, 2025, from https://www.globenewswire.com/news-release/2025/11/12/3186175/0/en/Remedy-Plan-Therapeutics-Advances-RPT1G-for-Myeloid-Cancer-Patients-with-Phase-1-Safety-Data-and-IND-Approval.html

[11] Precision BioSciences Presents Late-Breaking Phase 1 PBGENE-HBV Data at AASLD The Liver Meeting? Showing Safety, Tolerability and Cumulative, Dose-Dependent Antiviral Activity in First Three Cohorts. Retrieved November 14, 2025, from https://investor.precisionbiosciences.com/news-releases/news-release-details/precision-biosciences-presents-late-breaking-phase-1-pbgene-hbv

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