AL-01211

▎药明康德内容团队编辑本期看点1. 在一项1期研究中，T细胞受体（TCR）-T细胞疗法TSC-100和TSC-101与同种异体造血干细胞移植联用，让所有8名接受治疗的血液癌症患者没有出现复发。2. 肿瘤活化T细胞接合器JANX008的早期临床数据积极，一位接受JANX008治疗的非小细胞肺癌（NSCLC）患者100%的目标肺部病灶缩小。3. 治疗运动神经元病（MND）/肌萎缩侧索硬化（ALS）患者的小分子疗法monepantel的早期临床结果积极，高剂量组患者的疾病进展速率降低了58%。药明康德内容团队整理TSC-100、TSC-101：公布1期临床试验数据TScan Therapeutics公布了其开发的两种TCR-T细胞疗法TSC-100和TSC-101在1期临床试验中的更新数据。TSC-100和TSC-101是TScan Therapeutics公司开发的TCR-T细胞疗法，分别靶向次要组织相容性抗原HA-1和HA-2。它们旨在与同种异体的造血干细胞移植（HCT）联用，消灭残余血液癌细胞，预防疾病复发。此次公布的结果显示，所有8名接受TSC-100或TSC-101治疗的患者没有出现复发。其中，一名携带TP53基因突变的高风险骨髓增生异常综合征（MDS）患者在接受TSC-101治疗后已经无复发超过1年。JANX007、JANX008：公布1a期临床试验数据Janux Therapeutics公司公布了两项肿瘤活化T细胞接合器JANX007与JANX008的积极临床数据。JANX007是一款在研、潜在“best-in-class”的PSMA靶向肿瘤激活T细胞接合器，在临床上用于治疗转移性去势抵抗性前列腺癌（mCRPC），为Janux的主打项目。JANX008则是一种EGFR靶向肿瘤活化T细胞接合器，旨在克服患者产生细胞因子释放综合征（CRS）与已知的针对EGFR靶点的正常组织毒性问题。此次公布的分析结果显示，有83%接受JANX007治疗的晚期mCRPC患者达成前列腺特异性抗原（PSA）水平≥50%下降。一位接受JANX008治疗的NSCLC患者100%的目标肺部病灶缩小。根据此积极结果，Janux将持续进行这些疗法的剂量优化试验。Monepantel：公布1期临床试验数据PharmAust公司宣布，monepantel用于治疗运动神经元病/肌萎缩侧索硬化（俗称“渐冻症”）患者的1期临床试验达到了安全性和耐受性的主要终点，并显示出了具有潜在疗效的积极信号。此次公布的结果表明，monepantel的安全性和耐受性优于目前已获FDA批准的ALS/MND疗法。初步疗效数据显示，根据FDA主要疗效终点ALS功能评分量表修订版（ALSFRS-R），monepantel高剂量组患者的疾病进展速率降低了58%。该研究还证实了在患者的脑脊液中均可检测到monepantel及其活性代谢物。▲该1期临床试验的结果（图片来源：参考资料[14]）CYP-006TK：公布1期临床试验的初步数据Cynata Therapeutics公司公布了CYP-006TK治疗糖尿病足溃疡（DFU）的1期临床试验的首批16名患者伤口表面积的初步分析结果。CYP-006TK是Cynata公司的Cymerus诱导多能干细胞（iPSC）衍生间充质干细胞外用伤口敷料候选产品，它将间充质干细胞植入到一种新型硅敷料上。在这项试验中，CYP-006TK作为一种促进DFU患者伤口愈合的潜在治疗方法，受试者被随机分配接受以下两种治疗：（1）CYP-006TK治疗四周，然后在剩余的研究期间接受标准护理治疗；（2）在整个研究期间接受标准护理治疗。治疗10周后，CYP-006TK组（n=8）患者伤口表面积减少的百分比中位数为87.6%，而对照组（n=8）患者的这一比例为51.1%。这些结果与2023年4月公布的本试验首批6名患者（每组3人）截至第28天的结果所观察到的趋势一致。GDA-201：公布1期临床试验的初步数据Gamida Cell公司公布了其自然杀伤（NK）细胞疗法候选药物GDA-201的1期研究的首批12名CD20阳性非霍奇金淋巴瘤患者的初步数据。GDA-201可以通过增加细胞毒性以及在骨髓和淋巴器官中的扩增数量和留存时间来解决NK细胞疗法的局限性。此外，GDA-201还改善了NK细胞的抗体依赖性细胞毒性和肿瘤靶向性。入组患者之前接受过中位线数为六线的治疗，包括CAR-T细胞疗法和造血干细胞移植。患者接受了GDA-201联用利妥昔单抗的治疗，没有出现输液反应、剂量限制性毒性或相关严重不良事件。初步结果显示，7名患者的肿瘤负荷有所减轻。疗效评估显示，3名患者达到完全缓解（CR），2名患者达到部分缓解（PR），2名患者保持病情稳定（SD）。2名患者出现CRS（分别为1级和2级），没有出现免疫效应细胞相关神经毒性综合征（ICANS）或移植物抗宿主病（GvHD）的病例报告。该试验的全部结果预计将于2024年第一季度公布。AL01211：公布1期临床试验的初步数据AceLink Therapeutics公司公布了其用于治疗法布里病的新型GCS抑制剂在健康受试者中的1期临床试验数据。AL01211具有优秀的效力（个位数纳摩尔半抑制浓度IC50）、高选择性和其他良好的、可支持每日一次口服的药物特性，为目前需频繁静脉注射酶替代疗法的法布里病患者提供了口服小分子疗法的潜在选择。此次公布的结果显示，AL01211的安全性和耐受性良好。AL01211显示出剂量依赖性的药代动力学特征，能够有效降低健康受试者体内的疾病生物标志物的含量，如葡萄糖神经酰胺（glucosylceramide）和三己糖酰基鞘脂醇（globotriaosylceramide）。NT219：公布1/2期临床试验数据Purple Biotech公司公布了其潜在“first-in-class”的IRS1/2和STAT3双重抑制剂NT219的一项1/2期临床试验的新数据。这项1/2期研究旨在评估NT219联用西妥昔单抗治疗复发/转移性头颈部鳞状细胞癌（SCCHN）的安全性、药代动力学、药效学和疗效。该研究中，17名复发/转移性SCCHN患者既往接受治疗的中位线数为2线，94%的患者既往接受过免疫疗法。截至2024年1月25日的数据，患者对该联合疗法的耐受性和安全性良好。最常见的不良事件是输液相关反应和恶心，没有观察到与治疗相关的4/5级不良事件。药代动力学分析表明，NT219血浆浓度的增加与剂量有关。15名患者接受了疗效评估，其中7名患者观察到了抗肿瘤活性。在这7名患者中，2人确诊PR，3人达到SD（所有PR和SD的患者均为HPV阴性），客观缓解率（ORR）为29%，疾病控制率（DCR）为71%。所有剂量组患者的中位随访时间为9.4个月，15名患者中有8名仍在随访中。MaaT033：公布1期临床试验数据MaaT Pharma公司宣布，独立数据安全与监控委员会（DSMB）审查了IASO临床试验中使用MaaT033治疗的首批8位肌萎缩侧索硬化患者的安全性数据。MaaT033是一种源自供体、高浓度、高多样性的口腔微生物群生态系统疗法（Microbiome Ecosystem Therapy），目前正作为一种辅助疗法进行开发，以提高接受HCT和其他细胞疗法的患者的总生存率。此前，MaaT033已被欧洲药品管理局（EMA）授予孤儿药资格。此次DSMB的结论是，MaaT033的安全性良好，没有观察到严重不良事件，也没有发现可能与MaaT033有关的感染性事件，建议继续进行试验，不做任何修改。大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看）[1] Frontier Medicines Announces Oversubscribed $80 Million Series C Financing to Support Progress of Clinical-Stage Pipeline. Retrieved February 23, 2024 from https://www.frontiermeds.com/newsroom/press-releases/frontier-medicines-announces-oversubscribed-80-million-series-c-financing[2] Gamida Cell Data Presented at the 2024 Tandem Meetings of ASTCT® and CIBMTR. Retrieved February 26, 2024 from https://investors.gamida-cell.com/news-releases/news-release-details/gamida-cell-data-presented-2024-tandem-meetings-astctr-and/[3] Expert Systems Celebrates Completion of Single Dose Studies and Start of Multiple Human Dosing for Lomonitinib, a Selective Pan-FLT3/IRAK4 Inhibitor, Achieved in Just 3 Years. Retrieved February 26, 2024 from https://www.prnewswire.com/news-releases/expert-systems-celebrates-completion-of-single-dose-studies-and-start-of-multiple-human-dosing-for-lomonitinib-a-selective-pan-flt3irak4-inhibitor-achieved-in-just-3-years-302069988.html[4] TScan Therapeutics Presents Promising Updated Phase 1 Clinical Results on TSC-100 and TSC-101 at the 2024 Tandem Meetings of ASTCT and CIBMTR. Retrieved February 26, 2024 from https://www.globenewswire.com/news-release/2024/02/26/2835007/0/en/TScan-Therapeutics-Presents-Promising-Updated-Phase-1-Clinical-Results-on-TSC-100-and-TSC-101-at-the-2024-Tandem-Meetings-of-ASTCT-and-CIBMTR.html[5] AceLink Therapeutics Announces Publication of Phase 1 Clinical Trial Data Evaluating AL01211 in Healthy Volunteers. Retrieved February 26, 2024 from https://www.businesswire.com/news/home/20240226569957/en[6] Kura Oncology Doses First Patient in KOMET-008 Trial of Ziftomenib in Combination with Standards of Care, Including FLT3 Inhibitor, in Acute Myeloid Leukemia. Retrieved February 26, 2024 from https://ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-doses-first-patient-komet-008-trial-ziftomenib[7] Encouraging Initial Data from CYP-006TK Diabetic Foot Ulcer Clinical Trial. Retrieved February 26, 2024 from https://www.prnewswire.com/news-releases/encouraging-initial-data-from-cyp-006tk-diabetic-foot-ulcer-clinical-trial-302070709.html[8] Purple Biotech Presents Data of its Phase 1 Head & Neck Cancer of NT219 in combination with Cetuximab at ESMO TAT Congress 2024. Retrieved February 28, 2024 from https://www.globenewswire.com/news-release/2024/02/27/2835842/0/en/Purple-Biotech-Presents-Data-of-its-Phase-1-Head-Neck-Cancer-of-NT219-in-combination-with-Cetuximab-at-ESMO-TAT-Congress-2024.html[9] Janux Announces Encouraging Safety and Efficacy Data in Ongoing Dose Escalation Trials for PSMAxCD3-TRACTr JANX007 in mCRPC and EGFRxCD3-TRACTr JANX008 in Solid Tumors. Retrieved February 27, 2024 from https://investors.januxrx.com/investor-media/news/news-details/2024/Janux-Announces-Encouraging-Safety-and-Efficacy-Data-in-Ongoing-Dose-Escalation-Trials-for-PSMAxCD3-TRACTr-JANX007-in-mCRPC-and-EGFRxCD3-TRACTr-JANX008-in-Solid-Tumors/default.aspx[10] Curadev Announces First Treatment Cycle Completion for the First Patient Dosed in a Phase 1a/b Clinical Trial of its Allosteric STING Agonist CRD3874-SI in Patients with Advanced Cancer at Memorial Sloan Kettering Cancer Center in New York. Retrieved February 27, 2024 from https://www.prnewswire.com/news-releases/curadev-announces-first-treatment-cycle-completion-for-the-first-patient-dosed-in-a-phase-1ab-clinical-trial-of-its-allosteric-sting-agonist-crd3874-si-in-patients-with-advanced-cancer-at-memorial-sloan-kettering-cancer-center-in-302071911.html[11] Gain Therapeutics Announces the Initiation of the Multiple Ascending Dose (MAD) Part of the Phase 1 Clinical Trial of GT-02287, a Novel GCase-targeting Small Molecule Therapy for GBA1 Parkinson’s Disease. Retrieved February 27, 2024 from https://www.globenewswire.com/news-release/2024/02/27/2836361/0/en/Gain-Therapeutics-Announces-the-Initiation-of-the-Multiple-Ascending-Dose-MAD-Part-of-the-Phase-1-Clinical-Trial-of-GT-02287-a-Novel-GCase-targeting-Small-Molecule-Therapy-for-GBA1.html[12] ARTHEx Biotech Receives IND Clearance from FDA to Initiate the Phase I-IIa ArthemiR™ Trial of ATX-01 for Myotonic Dystrophy Type 1 (DM1). Retrieved February 29, 2024 from https://www.prnewswire.com/news-releases/arthex-biotech-receives-ind-clearance-from-fda-to-initiate-the-phase-i-iia-arthemir-trial-of-atx-01-for-myotonic-dystrophy-type-1-dm1-302073670.html[13] Spero Therapeutics Announces Clearance of IND for SPR206 to Treat MDR Gram-negative Bacterial Infections. Retrieved February 29, 2024 from https://www.globenewswire.com/news-release/2024/02/28/2836936/0/en/Spero-Therapeutics-Announces-Clearance-of-IND-for-SPR206-to-Treat-MDR-Gram-negative-Bacterial-Infections.html[14] PharmAust announces positive Phase 1 MEND Study Top-Line Results in MND / ALS. Retrieved February 29, 2024 from https://www.prnewswire.com/news-releases/pharmaust-announces-positive-phase-1-mend-study-top-line-results-in-mnd--als-302074155.html[15] Skyhawk Therapeutics Has Advanced to the Multiple Ascending Dose Portion of its Phase 1 Study evaluating SKY-0515, a RNA-Targeting Small Molecule for Huntington's Disease. 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Retrieved February 29, 2024 from https://www.businesswire.com/news/home/20240229517711/en[19] S.BIOMEDICS completes brain transplant of hESC-derived dopaminergic progenitors (TED-A9) for Phase 1/2a study in patients with Parkinson’s disease. Retrieved February 29, 2024 from https://www.businesswire.com/news/home/20240229508525/en免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

- This first in human clinical study demonstrated that AL01211 was generally safe and well-tolerated at single doses up to 60 mg and at multiple doses up to 30 mg - AL01211 displayed dose dependent pharmacokinetics and the ability to effectively reduce the disease biomarkers glucosylceramide and globotriaosylceramide in healthy volunteers - Topline results from a Phase 2 study of AL01211 in patients with Fabry disease are expected in the second half of 2024 NEWARK, Calif.--(BUSINESS WIRE)-- AceLink Therapeutics, Inc., a clinical-stage biopharmaceutical company developing next generation oral substrate reduction therapies (SRTs), today announced that the findings from their Phase 1 study of AL01211 in healthy volunteers have been published in the peer-reviewed journal Clinical Pharmacology in Drug Development, a journal of the American College of Clinical Pharmacy. AL01211 is a potent, oral, glucosylceramide synthase (GCS) inhibitor being developed for the treatment of Fabry disease and Type 1 Gaucher disease. In contrast to other GCS inhibitors in development, AL01211 has minimal central nervous system penetration (CNS), allowing therapeutic benefits to peripheral organs while avoiding the risk of CNS-associated adverse effects. “These results highlight the transformative potential of AL01211 as a best-in-class GCS inhibitor,” said Jerry Shen, Ph.D., Chief Executive Officer and Founder of AceLink Therapeutics. “Our Phase 1 study provided the critical safety and biomarker data to support our ongoing Phase 2 clinical trial in patients with Fabry Disease. We expect to have topline results of the Phase 2 trial in the second half of 2024.” In the published Phase 1 study, AL01211 was evaluated with a single ascending dose arm and a multiple ascending dose arm to determine the safety, pharmacokinetics (PK), and pharmacodynamic (PD) effects in healthy volunteers. Overall, AL01211 was generally safe and well-tolerated with no serious adverse events. At a 30 mg dose level, plasma glucosylceramide and globotriaosylceramide were reduced from baseline levels by 78% and 52%, respectively, thus supporting AL01211’s further clinical development. “These data reinforce our commitment to provide more convenient and more effective therapeutic options to patients suffering from glycosphingolipid storage diseases such as Fabry disease,” said Michael Babcock, Ph.D., VP of Research and Early Development. “In our trial, AL01211 demonstrated dose-dependent PK and PD effects with a clear correlation between AL01211 exposure and reduction in disease biomarkers. The insights gained from this study have set us up nicely to test the therapeutic benefits of AL01211 in patients.” In October 2023, AceLink Therapeutics dosed its first patient in a Phase 2 open-label study evaluating the safety, PK, and PD of AL01211 in males with classic Fabry disease who have not been previously treated. Topline results from this study are expected in the second half of 2024. About AL01211 AL01211 is a proprietary, non-brain penetrant GCS inhibitor with excellent potency (single-digit nanomolar IC50), great selectivity, and other favorable drug properties that support once-daily oral administration. AL01211 offers a much-needed oral small molecule therapy as an alternative to the frequent intravenous infusions required with enzyme replacement therapy. About GCS inhibitors GCS catalyzes the first step in the synthesis of glycosphingolipids, a group of bioactive molecules that play important roles in various cellular processes and diseases. GCS inhibitors reduce the synthesis of glycosphingolipids, thereby exerting beneficial effects to diseases such as Fabry and Gaucher disease, which are caused by the pathogenic accumulation of these lipids. About AceLink Therapeutics, Inc. Founded in 2018, AceLink Therapeutics is an innovative biopharma startup focusing on developing safe and effective medicines to address genetic diseases with high unmet needs. The company’s initial focus is to develop novel therapeutics for Fabry disease. For more information, please visit .