AGN-232411

▎药明康德内容团队编辑本期看点1. 新型胰高血糖素样肽1（GLP-1）受体激动剂GL0034的早期临床结果亮眼，健康受试者接受每周一次的治疗，8周最高减重10.7%。2. 用于治疗代谢综合征及其相关并发症的小分子CB1受体阻滞剂INV-202在28天的治疗期内使受试者的体重平均下降7斤，血脂和血糖控制指标也有所改善。3. 具有功能性治愈糖尿病潜力的干细胞疗法VX-880公布新临床试验数据，所有6名接受VX-880治疗的患者产生了内源性胰岛素，血糖控制得到了改善，同时减少或免除了胰岛素的使用。药明康德内容团队整理GL0034：公布首次人体试验的初步数据Sun Pharmaceutical Industries公司公布了其新型胰高血糖素样肽1受体（GLP-1R）激动剂GL0034的首次人体试验的初步数据。GL0034旨在作为一种每周一次的长效抗糖尿病药物，治疗2型糖尿病和肥胖患者。此次公布的两项试验的结果显示，GL0034在受试者中的耐受性良好。在其中一项研究中，无糖尿病的肥胖患者在接受单次用药后的第8天就观察到了甘油三酯水平和体重的下降。在另一项研究中，体重正常的健康受试者每周接受较低剂量的GL0034一次，持续8周，在GL0034治疗4至8周后，观察到受试者出现明显的剂量依赖性体重下降，最高达10.7%。在这些研究中，最常见的不良事件（任何剂量组中≥5名受试者）包括恶心、呕吐、食欲下降、早期饱食和消化不良。INV-202：公布1b期临床试验数据Inversago Pharma公司公布了其小分子CB1受体阻滞剂INV-202用于治疗代谢综合征及其相关并发症的1b期临床试验数据。INV-202旨在优先阻断肾脏、胃肠道、肝脏、胰腺、脂肪组织、肌肉、肺和其他外周组织中的CB1受体，从而治疗一系列心脏代谢疾病，包括糖尿病肾病。此次公布的结果显示，在28天的治疗期内，INV-202在具有代谢综合征特征的受试者中具有良好的安全性、耐受性、药代动力学和药效学作用。接受INV-202治疗的受试者显示出临床上显著的、渐进的体重下降，平均下降3.5公斤，而服用安慰剂的受试者的体重平均增加了0.55公斤（P<0.01）。此外，接受INV-202治疗的受试者相较于接受安慰剂的受试者在血脂和血糖控制方面也展现出积极的趋势，包括糖化血红蛋白（HbA1c）、甘油三酯和低密度脂蛋白胆固醇的降低。VX-880：公布1/2期临床试验数据Vertex Pharmaceuticals公司公布了其来源于干细胞的全分化胰岛细胞替代疗法VX-880在1/2期临床试验中获得积极数据。VX-880是一种来源于同种异体干细胞的全分化胰岛细胞疗法，有可能通过恢复胰岛细胞功能，包括葡萄糖反应性胰岛素的产生，来恢复机体调节葡萄糖水平的能力。VX-880通过肝门静脉输注给药，需要与慢性免疫抑制疗法联用来保护胰岛细胞免受免疫排斥。此次公布的数据显示，所有6名接受VX-880治疗的患者产生了内源性胰岛素，血糖控制得到了改善，同时减少或免除了胰岛素的使用。两名随访至少一年的患者符合主要终点的标准，即不再发生严重低血糖事件（SHE），HbA1c<7.0%。此外，这两名患者不再依赖外源胰岛素治疗，HbA1c值分别为5.3%和6.0%。截至目前，VX-880在所有患者中的耐受性良好。AMT-130：公布1/2期临床试验的新数据uniQure公司公布了其在研基因疗法AMT-130在治疗亨廷顿病（Huntington’s disease）的1/2期临床试验中获得积极初步结果。AMT-130是uniQure首个聚焦中枢神经系统的基因疗法，由AAV5载体携带专门沉默HTT基因表达的微RNA（microRNA），利用该公司专有的miQURE沉默技术，抑制突变亨廷顿蛋白的产生。在这项试验中，研究人员利用核磁共振（MRI）成像引导，将基因疗法直接注射到大脑的壳核和尾状核中。这是一种将基因疗法精准递送到中枢神经系统的技术。此次公布的结果显示，与基线时相比，接受AMT-130治疗的患者的功能得到了维持，与疾病自然史相比具有临床益处。脑脊液中的神经纤维蛋白轻链（NfL）水平是代表神经元损伤的关键生物标志物之一。在接受低剂量AMT-130治疗的患者中，NfL在24个月时降低至基线下；接受高剂量AMT-130治疗的患者，NfL在12个月时向基线下降。在低剂量队列中，患者脑脊液中的突变亨廷顿蛋白（mHTT）水平被抑制，高剂量队列中，这种抑制作用更强。NY-ESO-1 TCR/IL-15 NK：IND申请获得FDA许可NY-ESO-1 TCR/IL-15 NK是由Syena公司开发的工程化的T细胞受体自然杀伤（TCR-NK）细胞疗法，用于晚期滑膜肉瘤和粘液样/圆细胞脂肪肉瘤。该疗法使用源自脐带血的细胞，因此具潜力提供现货型、规模化的细胞疗法以治疗癌症。TCR-NK细胞疗法将工程化的TCR疗法与NK细胞结合，以改善其安全性与疗效。基于嵌合抗原受体（CAR）的疗法仅能辨认细胞表面的蛋白抗原，而TCR疗法则能辨认细胞内部的蛋白。将TCR与NK细胞结合使得细胞能够辨认由细胞表面免疫蛋白所呈现的外化蛋白片段。因此TCR-NK细胞疗法具潜力靶向范围更广的肿瘤抗原。该疗法的1/1b期临床试验计划于2023年第三季度启动。BI-1808：公布1/2a期临床试验的中期数据BioInvent International公司公布了其抗TNFR2抗体BI-1808用于治疗晚期恶性肿瘤的1/2a期试验的中期数据。TNFR2在肿瘤微环境的Treg细胞表面高表达，已被证明对肿瘤的生长和存活很重要，是癌症免疫疗法的一个新的有前途的靶点。此次公布的研究数据显示，BI-1808的安全性和耐受性良好，未观察到严重的不良事件或剂量限制性毒性。截至目前，22名可评估的患者中有6名达到了疾病稳定（SD）。Darovasertib（IDE196）：公布1期临床试验中首位患者的数据IDEAYA Biosciences公司公布了其在研蛋白激酶C（PKC）小分子抑制剂IDE196作为新辅助疗法在首位葡萄膜黑色素瘤（UM）患者中的病例报告。在这名UM患者中，darovasertib作为单一疗法进行新辅助治疗4个月后，肿瘤的大小缩小了24%，使患者免于接受眼球摘除手术。Itruvone（PH10）：公布1期临床试验数据Vistagen公司公布了其用于治疗抑郁症的在研鼻喷雾剂itruvone的积极早期数据。Itruvone鼻喷雾剂以微克级剂量施用，旨在结合和激活与大脑神经回路相连的鼻腔通道中的化学感觉神经元，从而产生抗抑郁作用。该候选疗法不需要全身摄取或脑渗透即可快速起效，从而有别于目前所有获批的口服抗抑郁药和快速起效的基于氯胺酮的治疗（KBT），有望避免与KBT和长效口服抗抑郁药有关的副作用和安全问题。此次公布的结果显示，itruvone的安全性和耐受性良好。AG-80308：公布1b期临床试验的初步数据Allgenesis Biotherapeutics公司公布了其用于治疗干眼病的甲酰肽受体（FPR）激动剂AG-80308在早期临床试验中的初步数据。该临床试验在84名干眼症患者中测试了不同种配方和浓度的AG-80308制剂。患者每天用药两次，持续3个月。结果显示，AG-80308在所有测试剂量下都被认为是安全的。患者在体征和症状方面都有改善，包括角膜染色、结膜染色、泪液分泌反应、干眼症不适、眼干、灼热/刺痛、瘙痒、异物感、畏光和疼痛。CHK-336：公布1期临床试验的初步数据Chinook Therapeutics公司公布了其用于治疗原发性高草酸尿症和其他肾结石疾病的口服小分子LDHA抑制剂CHK-336在健康受试者中的安全性、耐受性和药代动力学特征。1期临床试验结果显示，CHK-336通常耐受性良好，具有良好的药代动力学特征，其半衰期支持每日一次的给药频率。此外，研究人员利用新型示踪剂证明了CHK-336能够阻断健康受试者肝脏草酸盐的生成。EP262：公布1期临床试验数据Escient Pharmaceuticals公司公布了其潜在“first-in-class”的MRGPRX2受体小分子拮抗剂EP262的积极早期数据。MRGPRX2是一种在屏障组织（例如皮肤、气道、胃肠道）中发现的，并在肥大细胞上表达的受体。该受体激活会导致肥大细胞脱颗粒并释放组胺、类胰蛋白酶、糜蛋白酶、趋化因子和细胞因子，这会导致荨麻疹、血管性水肿、慢性瘙痒和疼痛等疾病。通过阻断MRGPRX2的激活，EP262有潜力治疗范围广泛的肥大细胞介导的疾病。此次公布的数据显示，EP262在所有测试剂量下都是安全且耐受性良好的，药代动力学特征支持每日一次口服给药。EDP-323：公布1期临床试验数据Enanta Pharmaceuticals公司公布了其用于治疗呼吸道合胞病毒（RSV）感染的新型口服L蛋白抑制剂EDP-323的积极早期数据。结果显示，800 mg剂量下连续7天给药EDP-323在健康受试者中的耐受性良好，药代动力学特征支持每天一次的给药频率。此外，所有剂量下EDP-323的暴露倍数（exposure multiples）均良好，支持EDP-323开展进一步的临床研究。VTP-300：公布1b/2期临床试验数据Vaccitech Limited公司宣布其针对慢性乙型肝炎（HBV）感染者的候选疫苗VTP-300在1b/2a期临床试验中达到了主要和次要终点。VTP-300是一种与疫苗作用机制非常类似的免疫疗法，利用Vaccitech的黑猩猩腺病毒载体（ChAdOx1）和改良牛痘安卡拉病毒（MVA）载体表达乙肝病毒抗原，激发抗HBV的免疫应答，有望为慢性乙肝患者带来功能性治愈。此次公布的数据显示，在单独接受VTP-300和与低剂量PD-1抑制剂联合使用的受试者中，观察到乙型肝炎表面抗原（HBsAg）显著、持久的降低。2名患者已检测不到HBsAg，在最后一次给药后维持了8个月。此外，VTP-300产生了强大的T细胞反应，这种反应在单独接受VTP-300的受试者中最高。大家都在看▲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，填写业务需求信息参考资料（可上下滑动查看）[1] Vaxxinity Announces UB-312 Successfully Met Primary Objectives of Phase 1 Clinical Trial in Parkinson’s Disease. Retrieved June 26, 2023, from https://ir.vaxxinity.com/news-releases/news-release-details/vaxxinity-announces-ub-312-successfully-met-primary-objectives[2] Jasper Therapeutics Announces First Patient Dosed in a Phase 1 Trial of Briquilimab in Lower-Risk Myelodysplastic Syndrome. Retrieved June 26, 2023, from https://ir.jaspertherapeutics.com/news-releases/news-release-details/jasper-therapeutics-announces-first-patient-dosed-phase-1-trial[3] CureVac Doses First Patient in Phase 1 Study of Cancer Vaccine Candidate for Surgically Resected Glioblastoma. Retrieved June 26, 2023, from https://www.accesswire.com/762253/CureVac-Doses-First-Patient-in-Phase-1-Study-of-Cancer-Vaccine-Candidate-for-Surgically-Resected-Glioblastoma[4] Accutar Biotechnology Announces First Patient Dosed with AC0676 in Phase 1 Study in Patients with Relapsed/Refractory B-cell Malignancies. Retrieved June 26, 2023, from https://www.businesswire.com/news/home/20230620086924/en[5] Delix Therapeutics Announces Completion of 1st Cohort Dosing, Dose Escalation Approval in Phase I Trial for Novel Compound DLX-001. Retrieved June 26, 2023, from https://www.prnewswire.com/news-releases/delix-therapeutics-announces-completion-of-1st-cohort-dosing-dose-escalation-approval-in-phase-i-trial-for-novel-compound-dlx-001-301853647.html[6] Chinook Therapeutics Presents Data from CHK-336 Phase 1 Trial in Healthy Volunteers and New Insights into the Role of Failed Repair in Chronic Kidney Disease at the 60th European Renal Association (ERA) Congress. Retrieved June 26, 2023, from https://www.globenewswire.com/news-release/2023/06/17/2689976/35377/en/Chinook-Therapeutics-Presents-Data-from-CHK-336-Phase-1-Trial-in-Healthy-Volunteers-and-New-Insights-into-the-Role-of-Failed-Repair-in-Chronic-Kidney-Disease-at-the-60th-European-R.html[7] Allgenesis Announces Encouraging Phase 1b Data Showing AG-80308 Providing Improvements in Multiple Signs and Symptoms in Dry Eye Patients. Retrieved June 26, 2023, from https://www.prnewswire.com/news-releases/allgenesis-announces-encouraging-phase-1b-data-showing-ag-80308-providing-improvements-in-multiple-signs-and-symptoms-in-dry-eye-patients-301853236.html[8] Replay and MD Anderson announce FDA clearance of IND application for first-in-class T-Cell Receptor Natural Killer (TCR-NK) cell therapy for sarcoma. Retrieved June 26, 2023, from https://www.globenewswire.com/news-release/2023/06/20/2690890/0/en/Replay-and-MD-Anderson-announce-FDA-clearance-of-IND-application-for-first-in-class-T-Cell-Receptor-Natural-Killer-TCR-NK-cell-therapy-for-sarcoma.html[9] ZSun Pharma Presents Data from First-in-Human Phase 1 Studies of GL0034 at the American Diabetes Association 83rd Scientific Sessions. Retrieved June 26, 2023, from https://www.prnewswire.com/news-releases/sun-pharma-presents-data-from-first-in-human-phase-1-studies-of-gl0034-at-the-american-diabetes-association-83rd-scientific-sessions-301861402.html [10] Sun Pharma Presents Data from First-in-Human Phase 1 Studies of GL0034 at the American Diabetes Association 83rd Scientific Sessions. Retrieved June 26, 2023, from https://www.prnewswire.com/news-releases/sun-pharma-presents-data-from-first-in-human-phase-1-studies-of-gl0034-at-the-american-diabetes-association-83rd-scientific-sessions-301861402.html[11] Inversago Pharma Presents Data from Phase 1b Trial of INV-202, a Peripheral CB1r Blocker for Metabolic Syndrome, at the 83rd American Diabetes Association Scientific Sessions. Retrieved June 26, 2023, from https://www.businesswire.com/news/home/20230623384277/en[12] Vertex Presents Positive VX-880 Results From Ongoing Phase 1/2 Study in Type 1 Diabetes at the American Diabetes Association 83rd Scientific Sessions. Retrieved June 26, 2023, from https://www.businesswire.com/news/home/20230623446641/en[13] Vistagen Announces Results of Successful U.S. Phase 1 Study of Itruvone (PH10), Enabling U.S. Phase 2B Development for Treatment of Major Depressive Disorder. Retrieved June 26, 2023, from https://www.businesswire.com/news/home/20230621794406/en[14] BioInvent Reports Strong Interim Safety Data and Early Signs of Efficacy in Phase 1/2a Trial with anti-TNFR2 Antibody BI-1808 in Advanced Malignancies. Retrieved June 26, 2023, from https://www.accesswire.com/762658/BioInvent-Reports-Strong-Interim-Safety-Data-and-Early-Signs-of-Efficacy-in-Phase-12a-Trial-with-anti-TNFR2-Antibody-BI-1808-in-Advanced-Malignancies[15] Enanta Pharmaceuticals Announces Positive Data From a Phase 1 Clinical Study of EDP-323, an Oral, L-Protein Inhibitor in Development for the Treatment of Respiratory Syncytial Virus. Retrieved June 26, 2023, from https://www.businesswire.com/news/home/20230620911346/en[16] Escient Pharmaceuticals Announces Positive Results from Phase 1 Study of EP262, a First-in-Class Oral MRGPRX2 Antagonist for Mast Cell Mediated Disorders. Retrieved June 26, 2023, from https://www.businesswire.com/news/home/20230620558373/en[17] IDEAYA Announces First Reported Case of Uveal Melanoma Patient Spared Enucleation in Phase 1 Neoadjuvant IST with Darovasertib Monotherapy. Retrieved June 26, 2023, from https://www.prnewswire.com/news-releases/ideaya-announces-first-reported-case-of-uveal-melanoma-patient-spared-enucleation-in-phase-1-neoadjuvant-ist-with-darovasertib-monotherapy-301857515.html[18] uniQure Announces Update on U.S. Phase I/II Clinical Trial of AMT-130 Gene Therapy for the Treatment of Huntington’s Disease. Retrieved June 26, 2023, from https://www.uniqure.com/investors-media/press-releases[19] Vaccitech to Present Positive Final Data at EASL Congress for Phase 1b/2 HBV002 Study in Adults with Chronic Hepatitis B. Retrieved June 26, 2023, from https://investors.vaccitech.co.uk/news-and-events/news-releases/news-release-details/vaccitech-present-positive-final-data-easl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

ALHAMBRA, Calif. , June 19, 2023 /PRNewswire/ -- Allgenesis Biotherapeutics Inc., a clinical-stage specialty pharmaceutical company focused on developing novel ophthalmic drugs, today announced topline data from the company's Phase 1b clinical trial for AG-80308, a first-in-class, formyl peptide receptor (FPR) agonist formulated as an aqueous solution eye drop for the treatment of Dry Eye Disease (DED). The Phase 1b trial is a multi-center, double-masked study to evaluate the safety, tolerability, and dose-response of AG-80308 Formulation A 0.001%, 0.03%, or 0.1% and Formulation B 0.03% dosed twice daily for 3 months in 84 dry eye patients. AG-80308 was considered safe at all doses tested BID for 3 months. AG-80308 provided improvements in both signs and symptoms: Signs: improvements in corneal staining, conjunctival staining, and tear production responders Symptoms: improvements in the 7-item visual analog scale, including dry eye discomfort, eye dryness, burning/stinging, itching, foreign body sensation, photophobia, and pain. AG-80308 Formulation A 0.001% and Formulation B 0.03% provided the best overall safety, tolerability, and efficacy profile. "We are very encouraged with our data showing that patients are seeing improvements in multiple signs and symptoms from the Phase 1b trial as early as 2 weeks", said Dr. Madhu Cherukury, CEO of Allgenesis. "AG-80308 can offer dry eye patients an effective treatment that can be used long-term without the AEs associated with other therapies" added Dr. Cherukury. "With the positive results from the Phase 1b trial, we are looking forward to moving this program into Phase 2, where we will evaluate 2 doses of AG-80308 in formulation B against vehicle. This will be an ideal drug for treating chronic dry eye patients due to its unique MOA and excellent potency" said Dr. Sunil Patel, Chief Medical Officer Allgenesis. Allgenesis has begun preparations to support initiation of the Phase 2 trial in 1Q2024. For additional inquiries regarding collaboration and partnering opportunities related to AG-80308, please contact Jack Chang ([email protected]) or Sandy Lai ([email protected]) for more information. About Allgenesis Biotherapeutics Inc. Allgenesis is a clinical-stage biopharmaceutical company headquartered in Taipei, Taiwan. The company is focused on research and development of novel medicines for the treatment of eye diseases. Current projects in the pipeline include AG-73305, a potential blockbuster drug for the treatment of DME, nAMD, and other retinal diseases such as RVO and AG-80308 for Dry Eye Disease. About AG-80308 AG-80308 is a novel, first-in-class, formyl peptide receptor (FPR) agonist formulated as an aqueous solution eye drop for the treatment of inflammation associated with Dry Eye Disease (DED). The project was in-licensed from Allergan (now AbbVie) in May 2020. SOURCE Allgenesis Biotherapeutics Inc.