本期看點

1. 潛在“first-in-class”突變型鈣網蛋白（mutCALR）靶向單克隆抗體早期臨床數據積極，超80%骨髓增殖性腫瘤（MPN）患者達完全緩解（CR）。

2. 血漿激肽釋放酶單抗抑制劑navenibart用于治療遺傳性血管性水腫，在一項早期臨床試驗中使患者每月的發作率大幅降低，平均降幅達92%，降幅中位數達97%。

INCA033989：公布首個臨床研究數據

Incyte近日公布其創新療法INCA033989的首個臨床研究數據，該藥物為一款潛在“first-in-class”、mutCALR靶向單克隆抗體，用于治療攜帶此突變的骨髓增殖性腫瘤患者。數據顯示，在接受INCA033989治療的高危原發性血小板增多癥（ET）的患者中，各劑量組均實現了快速且持久的血小板計數正常化，高劑量組（>400 mg）患者應答更為顯著。其中，86%的患者達到完全或部分血液學緩解，82%達CR；89%（34/38）的可評估患者mutCALR等位基因頻率（VAF）降低，且21%（8/38）患者在僅接受3個治療周期后即實現超過50%的VAF下降。

單細胞DNA測序探索性研究進一步顯示，INCA033989能夠選擇性靶向并減少攜帶mutCALR的造血干祖細胞（CD34陽性）及髓紅系細胞，同時促進正常（野生型CALR）細胞的恢復，支持健康造血功能的重建。骨髓活檢結果亦驗證了這一機制，mutCALR陽性巨核細胞減少、陰性巨核細胞增加。安全性方面，INCA033989在24至2500 mg的全部劑量范圍內耐受性良好，無劑量限制性毒性（DLT），僅1例患者因治療伴發不良事件（TEAEs）停藥，另有1例發生劑量調整。最常見的TEAEs為疲勞（26.5%）和上呼吸道感染（20.4%），均為1-2級。

Navenibart（STAR-0215）：公布1b/2期臨床試驗長期開放標簽試驗的數據

Astria Therapeutics公司公布了其血漿激肽釋放酶單抗抑制劑navenibart治療遺傳性血管性水腫的1b/2期臨床試驗長期開放標簽試驗的數據。此次公布的結果顯示，患者每月的發作率大幅降低，平均降幅達92%，降幅中位數達97%。頻率為每3個月給藥一次組別患者的平均每月發作率降低了95%，而每6個月給藥一次組別患者的平均降幅為86%。安全性方面，navenibart總體耐受性良好，無嚴重的治療伴發不良事件，無停藥現象。

ELVN-001：公布1期臨床試驗的新數據

Enliven Therapeutics公司公布其小分子激酶抑制劑ELVN-001治療慢性粒細胞白血病（CML）患者的1期臨床試驗的新數據。ELVN-001是一種強效、高選擇性、潛在“best-in-class”的小分子激酶抑制劑，專門針對CML患者的致癌驅動因子BCR-ABL融合蛋白。ELVN-001還具有針對耐藥性最強的BCR-ABL1耐藥突變體T315I和其他已知耐藥突變體的活性。

截至2025年4月28日的數據，在53例可評估的患者中，47%（25/53）在24周時達到主要分子學緩解（MMR），其中最后一線治療時對酪氨酸激酶抑制劑（TKI）耐藥的患者中有41%（14/34）在24周時處于MMR，曾接受asciminib或ponatinib治療的患者中也有35%（12/34）在24周時處于MMR。所有達到或維持MMR的患者在數據截止時仍保持緩解。在該臨床試驗中所納入的患者群體此前接受過大量治療的情況下，ELVN-001與已獲批的針對BCR-ABL融合蛋白的TKI在1期試驗中所觀察到的MMR相比，結果依然更好。安全性方面，ELVN-001在所有劑量水平上繼續表現出良好的安全性和耐受性。

BMF-500：公布1期臨床試驗的初步數據

Biomea Fusion公司公布了其共價FLT3抑制劑BMF-500治療復發/難治性急性白血病的初步臨床數據。BMF-500是一種新型、口服可利用的、高效、具選擇性的FLT3共價小分子抑制劑。此前的研究表明，BMF-500潛在的脫靶風險較小，對活化的FLT3突變（包括

FLT3

BMF-500在治療

FLT3

FLT3

FLT3

Misetionamide（GP-2250）：公布1期臨床試驗的中期數據

Panavance Therapeutics公司公布了其小分子療法misetionamide（GP-2250）聯用吉西他濱治療晚期不可切除或轉移性胰腺導管腺癌患者1期臨床試驗的中期數據。Misetionamide具有獨特的作用機制，可抑制兩種致癌轉錄因子c-MYC和NFκB。此次公布的結果顯示，與單獨使用吉西他濱的歷史結果相比，接受misetionamide聯用吉西他濱治療患者的確認的緩解率、疾病穩定率和無進展生存期更優，約42%的患者達到部分緩解或疾病穩定。此外，misetionamide聯用吉西他濱的安全性良好，與單獨使用吉西他濱的預期毒性相比，沒有明顯的新毒性或加劇的毒性。

參考資料（可上下滑動查看）

[1] Enliven Therapeutics Announces Updated Positive Data from Phase 1 Clinical Trial of ELVN-001 in CML at EHA 2025 Congress. Retrieved June 20, 2025, from https://www.prnewswire.com/news-releases/enliven-therapeutics-announces-updated-positive-data-from-phase-1-clinical-trial-of-elvn-001-in-cml-at-eha-2025-congress-302481050.html

[2] Beam Therapeutics Announces New Data from BEACON Phase 1/2 Clinical Trial of BEAM-101 Supporting Differentiated Profile in Sickle Cell Disease (SCD) at European Hematology Association (EHA) 2025 Congress. Retrieved June 20, 2025, from https://www.globenewswire.com/news-release/2025/06/13/3098931/0/en/Beam-Therapeutics-Announces-New-Data-from-BEACON-Phase-1-2-Clinical-Trial-of-BEAM-101-Supporting-Differentiated-Profile-in-Sickle-Cell-Disease-SCD-at-European-Hematology-Associatio.html

[3] U.S. Food & Drug Administration (FDA) Approves Investigational New Drug (IND) Application for Myrio's Lead Product (PHOX2B PC-CAR T) for the Treatment of Neuroblastoma. Retrieved June 20, 2025, from U.S. Food & Drug Administration (FDA) Approves Investigational New Drug (IND) Application for Myrio's Lead Product (PHOX2B PC-CAR T) for the Treatment of Neuroblastoma

[4] Intellia Therapeutics Announces Positive Three-Year Data from Phase 1 Trial of Lonvoguran Ziclumeran (lonvo-z) in Patients with Hereditary Angioedema (HAE) at the European Academy of Allergy and Clinical Immunology Congress. Retrieved June 20, 2025, from https://www.globenewswire.com/news-release/2025/06/15/3099489/0/en/Intellia-Therapeutics-Announces-Positive-Three-Year-Data-from-Phase-1-Trial-of-Lonvoguran-Ziclumeran-lonvo-z-in-Patients-with-Hereditary-Angioedema-HAE-at-the-European-Academy-of-A.html

[5] Vial Initiating Phase 1 Healthy Volunteer Trial of VIAL-TL1A-HLE, a Novel Subcutaneous Half-Life Extended Anti-TL1A Antibody for the Treatment of IBD and Other Inflammatory and Fibrotic Diseases. Retrieved June 20, 2025, from https://vial.com/updates/pr/vial-initiating-phase-1-healthy-volunteer-trial-of-vial-tl1a-hle/?

[6] Lyell Immunopharma Announces Positive New Clinical Data Demonstrating High Rates of Durable Complete Responses from the Phase 1/2 Trial of LYL314 for the Treatment of Aggressive Large B-cell Lymphoma. Retrieved June 20, 2025, from https://www.globenewswire.com/news-release/2025/06/17/3100483/0/en/Lyell-Immunopharma-Announces-Positive-New-Clinical-Data-Demonstrating-High-Rates-of-Durable-Complete-Responses-from-the-Phase-1-2-Trial-of-LYL314-for-the-Treatment-of-Aggressive-La.html

[7] Azitra Reports Promising Safety Data from Phase 1b Trial in Netherton Syndrome. Retrieved June 20, 2025, from https://www.prnewswire.com/news-releases/azitra-reports-promising-safety-data-from-phase-1b-trial-in-netherton-syndrome-302483136.html

[8] 882-P - Eloralintide, a Selective, Long-Acting Amylin Receptor Agonist for Obesity—Phase 1 Proof of Concept. Retrieved June 16, 2025 from https://eppro02.ativ.me/src/EventPilot/php/express/web/planner.php?id=ADA25

[9] Positive Late-Breaking Data for Incyte’s First-in-Class mutCALR-targeted therapy INCA033989 in Essential Thrombocythemia Presented at EHA2025. Retrieved June 16, 2025 from https://investor.incyte.com/news-releases/news-release-details/positive-late-breaking-data-incytes-first-class-mutcalr-targeted

[10] Oncoinvent Announces Positive Final Data from Phase 1/2a Trial of Radspherin? in Patients with Colorectal Peritoneal Metastases. Retrieved June 16, 2025 from https://www.prnewswire.com/news-releases/oncoinvent-announces-positive-final-data-from-phase-12a-trial-of-radspherin-in-patients-with-colorectal-peritoneal-metastases-302484870.html

[11] Zealand Pharma announces positive topline results from 28-week Phase 1b trial with GLP-1/GLP-2 receptor dual agonist dapiglutide. Retrieved June 16, 2025 from https://www.globenewswire.com/news-release/2025/06/18/3101731/0/en/Zealand-Pharma-announces-positive-topline-results-from-28-week-Phase-1b-trial-with-GLP-1-GLP-2-receptor-dual-agonist-dapiglutide.html

[12] Spyre Therapeutics Announces Positive Interim Phase 1 Results for Two Next-Generation TL1A Antibody Programs, and Provides Clinical Development Updates Expected to Deliver 9 Phase 2 Readouts. Retrieved June 20, 2025 from https://www.prnewswire.com/news-releases/spyre-therapeutics-announces-positive-interim-phase-1-results-for-two-next-generation-tl1a-antibody-programs-and-provides-clinical-development-updates-expected-to-deliver-9-phase-2-readouts-302483628.html

[13] Centessa Pharmaceuticals Announces Clearance of Investigational New Drug Application (IND) for ORX142, a Novel Orexin Receptor 2 (OX2R) Agonist; Clinical Data in Acutely Sleep-Deprived Healthy Volunteers Planned for this Year. Retrieved June 20, 2025 from https://investors.centessa.com/news-releases/news-release-details/centessa-pharmaceuticals-announces-clearance-investigational-new

[14] Eolo Pharma Publishes First-in-Human Study in Nature Metabolism on Novel Obesity Drug Activating Energy-Burning Pathway. Retrieved June 20, 2025 from https://www.globenewswire.com/de/news-release/2025/06/16/3099684/0/en/Eolo-Pharma-Publishes-First-in-Human-Study-in-Nature-Metabolism-on-Novel-Obesity-Drug-Activating-Energy-Burning-Pathway.html

[15] Debiopharm’s ADC Research Gains Momentum With Launch of First-in-human Trial Assessing Debio 1562M in Acute Myeloid Leukemia Patients. Retrieved June 20, 2025 from https://www.businesswire.com/news/home/20250616081884/en/Debiopharms-ADC-Research-Gains-Momentum-With-Launch-of-First-in-human-Trial-Assessing-Debio-1562M-in-Acute-Myeloid-Leukemia-Patients

[16] Biomea Fusion Presents Updated Preliminary Clinical Data for Covalent FLT3 Inhibitor BMF-500 in Relapsed or Refractory Acute Leukemia at EHA 2025. Retrieved June 20, 2025 from https://investors.biomeafusion.com/news-releases/news-release-details/biomea-fusion-presents-updated-preliminary-clinical-data#:~:text=The%20presentation%20by%20Dr.%20Farhad%20Ravandi%20of%20The,inhibitor%2C%20in%20heavily%20pretreated%20patients%20with%20R%2FR%20AL.

[17] Panavance Therapeutics Announces Promising Misetionamide (GP-2250) Phase 1 Clinical Trial Interim Findings in Pancreatic Cancer at BIO 2025. Retrieved June 20, 2025, from https://panavance.com/press/panavance-therapeutics-announces-promising-misetionamide-gp-2250-phase-1-clinical-trial-interim-findings-in-pancreatic-cancer-at-bio-2025/

[18] Astria Therapeutics Announces Positive Initial Results from the ALPHA-SOLAR Long-Term Open-Label Trial of Navenibart in Hereditary Angioedema Patients at the European Academy of Allergy and Clinical Immunology Annual Congress. Retrieved June 20, 2025, from https://ir.astriatx.com/news-releases/news-release-details/astria-therapeutics-announces-positive-initial-results-alpha

[19] Johnson & Johnson's dual-targeting CAR T-cell therapy shows encouraging first results in large B-cell lymphoma. Retrieved June 20, 2025, from https://www.prnewswire.com/news-releases/johnson--johnsons-dual-targeting-car-t-cell-therapy-shows-encouraging-first-results-in-large-b-cell-lymphoma-302480701.html

[20] Galapagos Presented New Data at ICML 2025 From Cohort 3 of ATALANTA-1 in Relapsed/Refractory Indolent NHL Patients, Demonstrating High Complete Response and MRD Negativity Rates With CAR-T Candidate GLPG5101. Retrieved June 20, 2025, from https://www.globenewswire.com/news-release/2025/06/18/3101896/0/en/Galapagos-Presented-New-Data-at-ICML-2025-From-Cohort-3-of-ATALANTA-1-in-Relapsed-Refractory-Indolent-NHL-Patients-Demonstrating-High-Complete-Response-and-MRD-Negativity-Rates-Wit.html

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