▎藥明康德內容團隊編輯

本期看點

1. Solu Therapeutics公司創新細胞毒性靶向嵌合體（CyTAC）藥物STX-0712的1期臨床試驗已完成首例患者給藥。該類療法能夠靶向傳統療法難以作用的細胞表面蛋白。

2. 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1a期臨床試驗數據積極，約20天的半衰期有望實現每周一次或每月一次的口服給藥方案。

藥明康德內容團隊整理

STX-0712：1期臨床試驗完成首例患者給藥

Solu Therapeutics公司宣布完成4100萬美元的A輪融資，所得資金將用于推進其核心項目STX-0712的臨床評估、拓展其他管線，以及探索其細胞毒性靶向嵌合體和治療指數控制靶向嵌合體（TicTAC）平臺的新應用。該公司還宣布啟動了STX-0712用于治療耐藥/難治性慢性粒單核細胞白血病（CMML）和其他血液系統惡性腫瘤的1期臨床試驗，首位患者已開始給藥。

Solu Therapeutics公司通過以獨特的方式將強效、選擇性小分子與效應抗體連接起來，能夠靶向傳統療法難以作用的細胞表面蛋白（如G蛋白偶聯受體和離子通道）。其雙功能小分子的一只臂可特異性進入細胞表面蛋白中的深結合口袋，另一臂通過專有連接子技術與其專有的抗體連接，可增強效應抗體的療效。

STX-0712是一種CyTAC藥物，通過靶向G蛋白偶聯受體CCR2（在惡性單核細胞中高表達），能夠清除CCR2陽性細胞，同時減少對正常細胞的影響，有望為耐藥/難治性血液腫瘤提供更精準、有效的治療選擇。臨床前數據顯示，STX-0712對CMML患者樣本中的CCR2陽性單核細胞具有強大的離體活性。

ABI-5366：公布1a期臨床試驗的中期數據

Assembly Biosciences公司公布了一種用于復發性生殖器皰疹的長效解旋酶-引物酶抑制劑ABI-5366的1a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，ABI-5366在口服劑量高達350毫克時耐受性良好，未報告3級或4級治療相關實驗室異?；驀乐夭涣际录?。此外，在所有劑量組中觀察到ABI-5366的半衰期約為20天，有望實現每周一次或每月一次的口服給藥方案。

CVN293：公布1期臨床試驗數據

Cerevance公司公布了其鉀雙孔結構域通道亞家族K成員13（KCNK13）抑制劑CVN293的積極1期臨床試驗結果。CVN293是一種高選擇性口服KCNK13抑制劑，旨在通過抑制神經炎癥減緩神經退行性疾病進展。KCNK13是一種潛在的NLRP3炎性小體激活的新型調節因子，該靶點由Cerevance公司專有的NETSseq平臺發現。

此次公布的研究結果顯示，接受CVN293單次和14天內多次給藥的健康成人對該藥物的耐受性良好，100%的受試者完成了試驗，未出現劑量限制性毒性、治療相關停藥或具臨床意義的生命體征異常，所有不良事件均為輕度。CVN293還顯示出強大的腦滲透性，支持KCNK13抑制劑對以神經炎癥為特征的神經退行性疾病的效用。

PALI-2108：1a期臨床試驗完成受試者給藥

Palisade Bio公司宣布，其用于治療潰瘍性結腸炎（UC）的在研藥物PALI-2108已完成1a期臨床試驗，預計將于2025年5月底公布頂線數據。在UC和纖維狹窄型克羅恩?。‵SCD）中，較高的PDE4B表達與局部炎癥活動有關。PALI-2108是一種PDE4抑制劑前藥，能在UC和FSCD等疾病部位局部活化，顯著提升病變組織內PDE4抑制劑濃度，同時減少全身暴露，從而降低腹瀉等傳統PDE4抑制劑的副作用。

初步結果顯示，迄今為止未觀察到與實驗室檢查或心電圖相關的嚴重不良事件或治療伴發不良事件。在臨床前研究中，與其他PDE4抑制劑相比，PALI-2108對PDE4 B和D有很強的抑制作用。這些結果表明，在劑量相當的情況下，PALI-2108具有極佳的耐受性。

ALX2004：IND申請獲得FDA許可

ALX Oncology公司宣布，其針對EGFR表達實體瘤的潛在“best-in-class”及“first-in-class”抗體偶聯藥物（ADC）ALX2004的IND申請已獲FDA批準，計劃于2025年中期啟動單劑量遞增及擴展的1期臨床試驗。ALX2004是通過該公司專有的拓撲異構酶I抑制劑有效載荷平臺設計的，由三部分組成，分別是經優化的抗EGFR抗體骨架、穩定性增強的連接子，以及能產生強旁觀者效應的專有拓撲異構酶I載荷，旨在克服早期EGFR靶向ADC因藥物設計、脫靶毒性及傳統載荷局限性導致的臨床瓶頸。

CVHNLC：IND申請獲得FDA許可

CureVac公司宣布，美國FDA已批準其基于mRNA的精準免疫療法CVHNLC的IND申請，可啟動針對鱗狀非小細胞肺癌（sqNSCLC）患者的1期研究。CVHNLC由兩種編碼8種在sqNSCLC中常見的腫瘤相關抗原（TAA）的mRNA構建體組成，其中4種為已知的實體瘤相關抗原，另4種為CureVac專有發現平臺鑒定的新TAA。該療法采用第二代mRNA骨架，使用未修飾的mRNA封裝于脂質納米顆粒（LNP）中。該公司計劃將CVHNLC與免疫檢查點抑制劑pembrolizumab聯用進行臨床試驗，旨在放大靶向抗腫瘤免疫反應。

參考資料（可上下滑動查看）

[1] IDEAYA Biosciences Announces Phase 1/2 Expansion for IDE397 and Trodelvy? Combination in MTAP-Deletion Urothelial Cancer. Retrieved April 12, 2025, from https://www.prnewswire.com/news-releases/ideaya-biosciences-announces-phase-12-expansion-for-ide397-and-trodelvy-combination-in-mtap-deletion-urothelial-cancer-302425193.html

[2] ALX Oncology Receives IND Clearance from U.S. FDA for ALX2004, a Novel EGFR-targeted Antibody-drug Conjugate. Retrieved April 12, 2025, from https://ir.alxoncology.com/news-releases/news-release-details/alx-oncology-receives-ind-clearance-us-fda-alx2004-novel-egfr

[3] CureVac Receives U.S. FDA IND Clearance to Initiate Phase 1 Clinical Trial for Novel mRNA-Based Precision Immunotherapy in Squamous Non-Small Cell Lung Cancer. Retrieved April 12, 2025, from https://www.curevac.com/en/curevac-receives-u-s-fda-ind-clearance-to-initiate-phase-1-clinical-trial-for-novel-mrna-based-precision-immunotherapy-in-squamous-non-small-cell-lung-cancer/

[4] NKGen Biotech Presents Data from Phase 1/2a Clinical Trial of Troculeucel in Moderate Alzheimer’s Disease at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD? 2025). Retrieved April 12, 2025, from https://nkgenbiotech.com/nkgen-biotech-presents-data-from-phase-1-2a-clinical-trial-of-troculeucel-in-moderate-alzheimers-disease-at-the-international-conference-on-alzheimers-and-parkinsons-disease/

[5] Lexeo Therapeutics Announces Positive Interim Phase 1/2 Data for LX2006 in Friedreich Ataxia Cardiomyopathy Supporting Advancement to Registrational Study. Retrieved April 12, 2025, from https://www.globenewswire.com/news-release/2025/04/07/3056510/0/en/Lexeo-Therapeutics-Announces-Positive-Interim-Phase-1-2-Data-for-LX2006-in-Friedreich-Ataxia-Cardiomyopathy-Supporting-Advancement-to-Registrational-Study.html

[6] Palisade Bio Completes Dosing in Phase 1a Portion of Ongoing Phase 1a/b Study of PALI-2108. Retrieved April 12, 2025, from https://palisadebio.com/palisade-bio-completes-dosing-in-phase-1a-portion-of-ongoing-phase-1a-b-study-of-pali-2108/

[7] SciTech Development Announces 2nd FDA Approval of a Phase 1 a/b IND For ST-001. New IND Targets the Treatment of Relapsed/Refractory Small Cell Lung Cancer Following Its Previous Approval in the Treatment of T-Cell NHL. Retrieved April 12, 2025, from https://www.prnewswire.com/news-releases/scitech-development-announces-2nd-fda-approval-of-a-phase-1-ab-ind-for-st-001-new-ind-targets-the-treatment-of-relapsedrefractory-small-cell-lung-cancer-following-its-previous-approval-in-the-treatment-of-t-cell-nhl-302421487.html

[8] Cerevance Presents Positive Results from Phase 1 Study of CVN293 at American Academy of Neurology 2025 Annual Meeting. Retrieved April 12, 2025, from https://www.cerevance.com/media/cerevance-presents-positive-results-from-phase-1-study-of-cvn293-at-american-academy-of-neurology-2025-annual-meeting

[9] LifeMine Announces First Participant Dosed in First-in-human Phase 1 Clinical Trial of LIFE-001, Designed De Novo to Become a Field Dominating Immunosuppressive for Immune-mediated Disorders and Transplantation. Retrieved April 12, 2025, from https://www.businesswire.com/news/home/20250407523884/en/LifeMine-Announces-First-Participant-Dosed-in-First-in-human-Phase-1-Clinical-Trial-of-LIFE-001-Designed-De-Novo-to-Become-a-Field-Dominating-Immunosuppressive-for-Immune-mediated-Disorders-and-Transplantation

[10] Neurona Therapeutics Presents Positive Clinical Data Update from NRTX-1001 Cell Therapy Trial in Drug-resistant Epilepsy at American Academy of Neurology Annual Meeting. Retrieved April 12, 2025, from https://www.neuronatherapeutics.com/news/press-releases/040825/

[11] Opus Genetics Announces One-Month Clinical Data from Pediatric Patient in Phase 1/2 Trial of OPGx-LCA5 Gene Therapy in Inherited Retinal Diseases. Retrieved April 12, 2025, from https://ir.opusgtx.com/press-releases/detail/483/opus-genetics-announces-one-month-clinical-data-from-pediatric-patient-in-phase-12-trial-of-opgx-lca5-gene-therapy-in-inherited-retinal-diseases

[12] Cytora Reports Successful Results of Phase 1/2a Trial of Stem Cell Treatment for Diabetic Foot Ulcers. Retrieved April 12, 2025, from https://www.prnewswire.com/news-releases/cytora-reports-successful-results-of-phase-12a-trial-of-stem-cell-treatment-for-diabetic-foot-ulcers-302424359.html

[13] KSQ Therapeutics Announces First Patient Dosed in Phase 1/2 Study for KSQ-004EX, a CRISPR/Cas9-Engineered Tumor Infiltrating Lymphocyte (eTIL?) Therapy. Retrieved April 12, 2025, from https://www.globenewswire.com/news-release/2025/04/09/3058270/0/en/KSQ-Therapeutics-Announces-First-Patient-Dosed-in-Phase-1-2-Study-for-KSQ-004EX-a-CRISPR-Cas9-Engineered-Tumor-Infiltrating-Lymphocyte-eTIL-Therapy.html

[14] KSQ Therapeutics Announces First Patient Dosed in Phase 1/2 Study for KSQ-004EX, a CRISPR/Cas9-Engineered Tumor Infiltrating Lymphocyte (eTIL?) Therapy. Retrieved April 12, 2025, from https://www.globenewswire.com/news-release/2025/04/09/3058270/0/en/KSQ-Therapeutics-Announces-First-Patient-Dosed-in-Phase-1-2-Study-for-KSQ-004EX-a-CRISPR-Cas9-Engineered-Tumor-Infiltrating-Lymphocyte-eTIL-Therapy.html

[15] Solu Therapeutics Closes $41M Series A Financing and Announces First Patient Dosed in Phase 1 Clinical Trial of STX-0712 in Patients with CMML and Other Advanced Hematologic Malignancies. Retrieved April 12, 2025, from https://cdn.prod.website-files.com/669551ccc7908830b842dc2b/67f55ddc890a926ab1f047c9_Final%20Solu%20press%20release_4.9.pdf

[16] Context Therapeutics Doses First Patient in Phase 1 Clinical Trial of CT-95. Retrieved April 12, 2025, from https://www.globenewswire.com/news-release/2025/04/09/3058314/0/en/index.html

[17] Amylyx Pharmaceuticals Announces First Participant Dosed in Phase 1, Multiple Ascending Dose LUMINA Trial of AMX0114 in People Living with Amyotrophic Lateral Sclerosis. Retrieved April 12, 2025, from https://www.amylyx.com/news/amylyx-pharmaceuticals-announces-first-participant-dosed-in-phase-1-multiple-ascending-dose-lumina-trial-of-amx0114-in-people-living-with-amyotrophic-lateral-sclerosis

[18] Assembly Biosciences Presents New Data Highlighting Long-Acting Herpes Simplex Virus Candidate ABI-5366 and Genital Herpes Prevalence and Treatment Patterns at the 2025 ESCMID Congress. Retrieved April 12, 2025, from https://investor.assemblybio.com/news-releases/news-release-details/assembly-biosciences-presents-new-data-highlighting-long-acting

[19] Seismic Therapeutic Doses First Cohort in Phase 1 Clinical Trial of S-4321, a Novel Bifunctional Antibody that Agonizes PD-1 and FcγRIIb Inhibitory Receptors for the Treatment of Autoimmune Disease. Retrieved April 12, 2025, from https://seismictx.com/seismic-therapeutic-doses-first-cohort-in-phase-1-clinical-trial-of-s-4321-a-novel-bifunctional-antibody-that-agonizes-pd-1-and-fc%ce%b3riib-inhibitory-receptors-for-the-treatment-of-autoimmune-disea/

免責聲明：藥明康德內容團隊專注介紹全球生物醫藥健康研究進展。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。