AGLE-102

▎药明康德内容团队编辑本期看点1. 泛KRAS创新疗法ELI-002的1期临床结果积极，部分胰腺癌和结直肠癌患者的疾病进展风险降低86%。2. 骨髓检查点和重编候选药物NGM707联用帕博利珠单抗治疗晚期或转移性实体瘤患者，使1例微卫星稳定型结直肠癌患者获得病理完全缓解（CR）。3. 用于治疗深二度烧伤的细胞外囊泡疗法AGLE-102的早期临床结果积极，一次局部治疗即可使患者烧伤创面的上皮化率达到99%。4. Veru公司向美国FDA提交了其旨在帮助减脂不减肌的候选疗法enobosarm与胰高血糖素样肽-1（GLP-1）药物联用用于减肥的IND申请，以开展一项2b期临床试验。药明康德内容团队整理ELI-002：公布1期临床试验的新数据 Elicio Therapeutics公司公布了其在研治疗性癌症免疫疗法ELI-002治疗具高复发风险胰腺癌和结直肠癌患者的新临床试验数据，这些患者携带KRAS G12D和G12R突变。ELI-002由AMP修饰的KRAS突变体（mKRAS）肽段，和一种AMP修饰的免疫刺激寡核苷酸佐剂ELI-004组成，经皮下给药靶向淋巴结。它能产生RAS特异性杀伤性T细胞，以攻击术后残留肿瘤细胞，有望延长癌症患者缓解并可预防未来复发。截至2023年9月6日的数据，中位随访时间为8.5个月时，可评估患者（25人）的中位无复发生存期（RFS）为16.33个月。84%的患者（21/25）观察到KRAS突变体特异性T细胞应答，其中59%表现出CD4阳性和CD8阳性T细胞应答。84%的患者（21/25）观察到肿瘤生物标志物应答，6/25患者（24%；3名胰腺癌，3名结直肠癌）实现生物标志物清除。对于ELI-002诱导的T细胞应答程度高于中位数值的患者，其疾病进展或死亡风险降低了86%。安全性方面，ELI-002显示出良好的耐受性，没有剂量限制性毒性或≥3级的治疗相关不良事件。NGM707：公布1期临床试验的新数据 NGM Biopharmaceuticals公司公布了其骨髓检查点和重编候选药物NGM707联用帕博利珠单抗治疗晚期或转移性实体瘤患者的新临床数据。NGM707是一种靶向在骨髓细胞上富集表达的抑制性受体ILT2和ILT4的抗体药物。通过抑制ILT2和ILT4，NGM707有望克服两种受体在骨髓细胞中共表达的潜在冗余作用，并重新编程这些细胞以增强T细胞活性和增殖。此次公布的结果显示，NGM707在所有剂量队列中的耐受性均良好，并显示出有前景的抗肿瘤活性早期信号。截至2023年11月6日的数据，37例可评估患者的总缓解率（ORR）为11%，疾病控制率（DCR）为43%。其中，4例患者达到了确认的部分缓解（PR），12例患者达到了疾病稳定（SD），1例患者达到了病理CR。这名病理CR患者为微卫星稳定型结直肠癌患者，其靶病灶明显缩小，因此可以在随后的手术中切除所有残留病灶，并最终被确诊为病理CR，即无活性肿瘤细胞，没有侦测到循环肿瘤DNA（ctDNA）。AGLE-102：公布1/2a期临床试验的首例患者数据 Aegle Therapeutics公司公布了AGLE-102治疗深二度烧伤的1/2a期临床试验的首例入组患者12周的积极数据。AGLE-102是使用Aegle公司专有的方法从异体干细胞中分离出来的细胞外囊泡及其相关生物分子（如蛋白质、肽、配体和核酸）复杂组合的复合体，具有诱导受体细胞产生多种效应的潜力，包括减轻炎症、调节免疫系统和促进再生愈合。第一位患者在烧伤后48小时内接受了单剂量的AGLE-102局部治疗。患者烧伤创面的上皮化率达到99%，水肿也在治疗后七天内显著减轻，并且后续无需再使用AGLE-102。治疗一周后，通过激光多普勒测量，患者没有缺血再灌注损伤的迹象，也没有烧伤转化的迹象。患者和观察者疤痕评估量表（POSAS）的测量结果显示，患者在治疗后七天的疤痕明显改善，并在12周的随访中持续改善。到第90天，患者的POSAS评分（衡量疼痛、瘙痒、厚度、僵硬、颜色和不规则性）从基线时的40分改善到10分（6分为正常值）。此外，没有报告安全问题。Enobosarm：向FDA提交2期临床的IND申请 Enobosarm是Veru公司开发的一种选择性雄激素受体调节剂。近期，Veru公司向FDA提交了enobosarm与GLP-1药物联用用于减肥的IND申请，以开展一项2b期临床试验。由于现有GLP-1受体激动剂药物减轻的体重中有50%来自于肌肉的减少，患者有发生肌肉萎缩和出现肌无力的潜在风险。Enobosarm旨在与GLP-1受体激动剂联用，防止超重或肥胖患者（尤其是肌肉减少性肥胖或超重的老年患者）的肌肉流失，同时优先减少脂肪。AFM24：公布1/2a期临床试验的新数据Affimed公司公布了其先天细胞接合剂（innate cell engager，ICE）疗法AFM24用于治疗非小细胞肺癌（NSCLC）的新临床结果。该疗法靶向EGFR和CD16A。截至2024年1月4日的数据，在EGFR野生型NSCLC队列中，接受治疗的15名患者中有1例确认的CR、2例确认的PR和1例未确认的PR。这些患者此前接受过多线治疗，中位线数为2线，并且所有患者在接受PD-1/PD-L1靶向治疗后进展。根据这些积极结果，Affimed公司计划把EGFR野生型NSCLC队列的入组人数扩大到40例。JBI-802：公布1期临床试验的初步数据Jubilant Therapeutics公司公布了其在晚期癌症患者中进行1期试验的初步结果。该研究结果还为扩大JBI-802在伴有血小板增多的原发性血小板增多症和相关骨髓增生性肿瘤伴血小板增多症中的应用提供了人体概念验证。JBI-802是一种对LSD1和HDAC6具有双重活性的潜在“first-in-class”的CoREST（阻遏因子元件-1沉默转录共阻遏蛋白）抑制剂。临床前研究显示，在异种移植模型中，JBI-802联用免疫疗法可产生协同抗肿瘤效果。此外，据报道，CoREST抑制剂对免疫疗法耐药的肿瘤，尤其是STK11突变的肿瘤有增敏作用。首批11例晚期癌症患者的数据显示，不同组群的暴露量按剂量比例增加，暴露量与血小板减少的靶向效应之间存在很强的相关性，这表明LSD1抑制作用已达到药理学相关水平。同时，血小板减少是这些患者中观察到的唯一1级以上不良事件，这也是JBI-802与纯LSD1抑制剂的区别所在。此外，1例携带STK11突变的免疫检查点抑制剂难治性NSCLC患者在接受JBI-802治疗后达到确认的PR，靶病灶缩小了39%，pancoast综合征（影响臂丛神经的肺部病变）随之完全消退。目前，患者已接受了9个周期的JBI-802治疗，并且仍在继续接受治疗。还有1例免疫检查点抑制剂难治性NSCLC伴肝转移患者在接受BI-802治疗后，肝转移缩小了超过50%，相关门静脉高压、水肿得到完全缓解，患者的生活质量得到改善。Enitociclib：公布1期临床试验数据Vincerx Pharma公司公布了其高选择性CDK9抑制剂enitociclib与维奈托克（venetoclax）和泼尼松联用治疗复发/难治性淋巴瘤的1期临床试验的积极数据。Enitociclib可阻止RNA聚合酶II的活化，从而减少已知致癌基因MYC和MCL1的活性。此次公布的结果显示，3名外周T细胞淋巴瘤（PTCL）患者中有2例达到了PR。其中1名血管免疫母细胞性T细胞淋巴瘤患者接受联合治疗后，肿瘤负荷减少了91%，目前仍在接受随访。另1名PTCL患者仍处于研究中，其肺部病变缩小了86%，皮肤病变也得到了缓解。2名双发弥漫性大b细胞淋巴瘤（DH-DLBCL）患者中有1例达到了PR。这名患者在接受联合治疗后仅1周期就达到了PR，这突显了与enitociclib单药治疗相比，接受联合疗法的患者达到缓解的速度更快。研究人员对这种新型联合疗法的安全性感到满意，迄今为止未发现任何剂量限制性毒性反应，并将继续进行患者招募。VYN201：公布1b期临床试验的新结果VYNE Therapeutics公司公布了其用于治疗非节段性白癜风的在研新型BET抑制剂VYN201的新临床试验结果。VYN201是一种泛溴结构域BET抑制剂，通过局部给药降低其全身暴露量，用于治疗涉及多种不同炎症细胞信号通路的疾病。在临床前模型中，VYN201已被证明具有局部活性，能够持续减少促炎和疾病相关生物标志物，并改善疾病的严重程度。此次公布的数据显示，VYN201对白癜风相关关键生物标志物显示出积极作用。与基线相比，治疗8周后，VYN201诱导了活检皮损皮肤中基质金属蛋白酶-9（MMP-9）的下调。MMP-9是一种炎症性生物标志物，与白癜风患者皮肤黑色素细胞的脱落和随后的脱失有关，并且在白癜风患者中会升高。第8周时，与基线相比，2.0%剂量队列中受试者病变皮肤中MMP-9水平的中位数降低了40.8%。与基线相比，VYN201治疗8周后还诱导了多种黑色素细胞相关转录因子（MRTFs）上调，包括SOX10、LEF1、β-Catenin和MITF。这些标志物都与黑色素细胞的增殖、黑色素生成的恢复以及随后的皮肤色素沉着有关。在2.0%剂量队列中，与基线相比，病变皮肤中SOX10、LEF1、β-Catenin和MITF转录因子各自的表达水平的中位数分别增加了36.1%、90.2%、16.5%和15.2%。这些研究结果表明，VYN201有望通过下调MMP-9、上调与黑色素细胞增殖和黑色素生成相关的蛋白质的表达来减少黑色素细胞的脱落，从而治疗白癜风。VRG50635：启动1b期临床试验VRG50635是维智基因（Verge Genomics）开发的一种强效、可口服的PIKfyve抑制剂，能提高肌萎缩侧索硬化（ALS）患者神经元的存活率，并在ALS相关运动神经元变性模型的多项临床前研究中显示出疗效。PIKfyve是基于维智基因的人工智能（AI）平台CONVERGE在患病人体组织中发现的ALS治疗靶点。近日，维智基因宣布启动VRG50635治疗散发性和家族性ALS的1b期概念验证研究，该研究将评估VRG50635剂量递增的安全性和耐受性。根据新闻稿，VRG50635是首批进入临床的完全由人工智能平台发现和开发的药物之一，专门针对诸如ALS等中枢神经系统疾病进行了优化，有望成为潜在的“best-in-class”疗法。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] Xilio Therapeutics Highlights Recent Advances Across Clinical Pipeline and Encouraging Preliminary Phase 1 Safety Data for XTX301, a Tumor-Activated IL-12, Further Validating the Promise of Its Tumor-Activated Immuno-Oncology Therapies. 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[08-January-2024] First patient treated with AGLE-102 demonstrated 99% epithelialization in a deep second-degree burn within 7 days of receiving a single dose No evidence of burn wound conversion nor ischemia reperfusion injury as evidenced clinically and by laser doppler studies WOBURN, Mass. and MIAMI, Jan. 8, 2024 /PRNewswire/ -- Aegle Therapeutics Corp., a leader in the development of novel extracellular vesicle ("EV") therapies to treat rare and severe dermatological, including immuno-dermatological, conditions, today announced positive 12-week data for the first patient enrolled in a Phase 1/2a clinical trial of AGLE-102™ for the treatment of severe second-degree burns. The first patient was treated with a single topical dose of AGLE-102 within 48 hours of burn injury. The patient achieved 99% epithelialization of the burn wound and had a significant reduction in edema within seven days of treatment. Subsequent doses of AGLE-102 were not required. The patient had no evidence of ischemia reperfusion injury, as measured by Laser Doppler, one week post treatment, and no evidence of burn conversion was noted. Patient and Observer Scar Assessment Scale (POSAS) measurements showed significant improvement seven days post treatment and continued to improve over 12 weeks of follow-up. By day 90, the patient's POSAS score (which measures pain, itch, thickness, stiffness, color and irregularity) improved from a score of 40 at baseline to a score of 10 (6 being normal). No safety issues were reported. "We are very pleased with the first patient's results in this first-in-human trial of AGLE-102," said Shelley Hartman, Aegle's Chief Executive Officer. "This milestone highlights our commitment to advancing EV therapy as an important, novel, multi-faceted approach to treating rare and severe dermatological conditions." About AGLE-102TM AGLE-102 is an investigational product comprised of extracellular vesicles isolated from allogeneic stem cells using Aegle's proprietary and patented methods. The product is a composite of native EVs and their associated complex assemblies of biologic molecules such as proteins, peptides, ligands and nucleic acids that have the potential to induce a wide variety of effects in recipient cells, including reducing inflammation, modulating the immune system and promoting regenerative healing. About the Phase 1/2a Clinical Trial The phase I/2a trial, "A Pilot Safety Study of Mesenchymal Stem Cell Derived Extracellular Vesicles for the Treatment of Burn Wounds," is a prospective, single arm multi-center study designed to evaluate the safety and efficacy of applying AGLE-102 to deep second-degree burns. The program is being advanced for the discovery and development of allogeneic stem cell derived extracellular vesicle therapy that has the potential to offer patients reduced inflammation, accelerated regenerative healing (with minimal/no scarring) and prevention of burn conversion. More information on the phase 1/2a study (NCT05078385) is available at clinicaltrials.gov. About Aegle Therapeutics Corp. Aegle Therapeutics is a clinical-stage regenerative medicine biotechnology company developing novel EV therapies to treat rare and serious dermatological, including immuno-dermatological, disorders with significant unmet medical need. Aegle's proprietary platform technology safely isolates a broad composite of native EVs from stem cells. In addition to its phase 1/2a study in severe second-degree burns, Aegle's pipeline includes an anticipated launch of a phase 1/2a study in Q1 2024 evaluating AGLE-102 for the treatment of the rare disease epidermolysis bullosa and a preclinical program for graft vs. host disease. Aegle's EV therapy has the potential to treat a broad range of indications in multiple therapeutic areas in dermatology including inflammatory disorders, immune-based conditions and others. The anti-inflammatory and immune modulatory effects of Aegle's EV therapy also hold significant promise in the treatment of numerous other disorders in therapeutic areas outside of dermatology. For more information about Aegle Therapeutics, please visit . For More Information Contact: info@aegletherapeutics.com