Eloxx Pharmaceuticals Reports Additional Confirmation That All Nonsense Mutation Alport Syndrome Patients Treated With ELX-02 in Phase 2 Study Had Improvement in Kidney Morphology and Clinical Benefit of Reduction or Stabilization of Proteinuria
Eloxx Pharmaceuticals Reports Additional Confirmation That All Nonsense Mutation Alport Syndrome Patients Treated With ELX-02 in Phase 2 Study Had Improvement in Kidney Morphology and Clinical Benefit of Reduction or Stabilization of Proteinuria
ELX-02 treatment improved podocyte foot process effacement in all three patients by an average of 60% based on a blinded kidney biopsy analysis by NIPOKA GmbH
根据NIPOKA GmbH的盲肾活检分析，ELX-02 治疗使所有三名患者的足细胞足部脱落平均改善了60％
Biopsy results support clinical benefit in all three patients as improvement of kidney morphology is consistent with reduction or stabilization of proteinuria during or up to 2 months post completion of dosing
活检结果支持所有三名患者的临床益处，因为肾脏形态的改善与在给药完成后2个月内或最长2个月内蛋白尿的减少或稳定是一致的
Renowned key opinion leaders recommend continued development following review of clinical and biopsy results
著名的主要意见领袖建议在审查临床和活检结果后继续发展
WATERTOWN, Mass., Oct. 09, 2023 (GLOBE NEWSWIRE) -- Eloxx Pharmaceuticals, Inc. (NASDAQ: ELOX), a leader in ribosomal RNA-targeted genetic therapies for rare diseases, today reported results from an assessment of patient biopsies by NIPOKA GmbH (Nipoka). They have developed a highly accurate method for the quantification of podocyte foot process morphology. These results confirm previously reported positive biopsy results from the proof-of-concept Phase 2 open-label clinical trial (NCT05448755) of ELX-02 for the treatment of Nonsense Mutation Alport syndrome patients. Analysis of formalin-fixed paraffin-embedded (FFPE) biopsy samples by Nipoka show ELX-02 treatment improved podocyte foot process morphology with lower effacement in all three patients at the end of the 8-week study period.
马萨诸塞州沃特敦，2023年10月9日（GLOBE NEWSWIRE）——罕见病核糖体RNA靶向遗传疗法的领导者Eloxx Pharmicals, Inc.（纳斯达克股票代码：ELOX）今天公布了NIPOKA GmbH（Nipoka）对患者活检的评估结果。他们开发了一种高度准确的方法来量化足细胞足部过程形态。这些结果证实了先前报告的用于治疗胡说八道突变Alport综合征患者的 ELX-02 2期开放标签临床试验（NCT05448755）的活检阳性结果。Nipoka对福尔马林固定石蜡包裹（FFPE）活检样本的分析表明，在为期8周的研究期结束时，ELX-02 治疗改善了足细胞足部过程形态，所有三名患者的流失率都较低。
"With this accurate analysis of the patient biopsies and quantification of changes, we now have unequivocal evidence of morphology and clinical improvement in all three Nonsense Mutation Alport patients treated with ELX-02. Improvement in kidney morphology drives clinical benefit in this devastating rare disease," said Sumit Aggarwal, President and Chief Executive Officer of Eloxx. "We believe that our proteinuria data, during and after treatment, in the context of this improvement in kidney morphology, confirms clinical benefit in all three patients."
“通过对患者活检的准确分析和对变化的量化，我们现在有了明确的证据，表明所有三名接受 ELX-02 治疗的 Nonsense Mutation Alport 患者的形态学和临床改善。肾脏形态的改善推动了这种毁灭性的罕见疾病的临床益处。” Eloxx总裁兼首席执行官苏米特·阿格瓦尔说。“我们认为，在肾脏形态改善的背景下，我们在治疗期间和治疗后的蛋白尿数据证实了所有三名患者的临床益处。”
NIPOKA GmbH have developed a Podocyte Exact Morphology Procedure (PEMP) to quantify podocyte foot process morphology accurately and precisely in an unbiased and reproducible manner. PEMP utilizes immunostaining for foot-process specific protein markers followed by 3D-SIM imaging to quantify Filtration Slit Density (FSD) for 15 to 20 glomeruli per sample. FSD is a quantitative measure of the degree of podocyte foot process effacement. Higher FSD correlates with better podocyte health and lower podocyte foot process effacement. Healthy patients have an FSD of approximately 3.0 to 4.0. This analysis has been validated in multiple glomerular diseases.
NIPOKA GmbH 开发了一个 足细胞精确形态学程序 (PEMP) 以公正和可重复的方式准确、精确地量化足细胞足部过程形态。PEMP 利用免疫染色进行足部工艺特异性蛋白质标记，然后使用 3D SIM 成像来量化每个样本 15 到 20 个肾小球的过滤裂缝密度 (FSD)。FSD 是足细胞足部脱落程度的定量衡量标准。较高的 FSD 与更好的足细胞健康状况和较低的足细胞足部脱落有关。健康患者的 FSD 约为 3.0 到 4.0。该分析已在多种肾小球疾病中得到验证。
PEMP analysis confirmed that ELX-02 treatment improved podocyte foot process effacement in all three patients with an average post-treatment increase in FSD of 60% as compared to baseline levels. These findings are also consistent with previous Transmission Electron Micrograph (TEM) image assessments.
PEMP 分析证实，ELX-02 治疗改善了所有三名患者的足细胞足部脱落，与基线水平相比，治疗后的 FSD 平均增加了 60%。这些发现也与先前的透射电子显微镜（TEM）图像评估一致。
Differences in Urine Protein-Creatinine ratio (UPCR) changes across patients during treatment were correlated to severity of disease (lower vs. higher FSD) at baseline. Therefore, improvement in UPCR was assessed both during and 2 months after treatment to evaluate clinical benefit and capture the full effect of the 45-day protein half-life.
治疗期间患者尿蛋白-肌酐比率（UPCR）变化的差异与基线时的疾病严重程度（较低与较高的FSD）相关。因此，在治疗期间和治疗后两个月，都对UPCR的改善进行了评估，以评估临床益处并捕捉45天蛋白质半衰期的全部效果。
Patient |
FSD at end |
Average |
Average change in |
UPCR variability |
4401 – 01 |
1.50 (50%) |
No change |
No Change |
-32% |
4401 – 02 |
1.75 (13%) |
-49%; |
No Change |
-46% |
4402 – 01 |
1.73 (118%) |
No change |
-25% |
-68% |
病人 |
最后是 FSD |
平均值 |
平均变化 |
UPCR 可变性 |
4401 — 01 |
1.50 (50%) |
没有变化 |
没有变化 |
-32% |
4401 — 02 |
1.75 (13%) |
-49%； |
没有变化 |
-46% |
4402 — 01 |
1.73 (118%) |
没有变化 |
-25% |
-68% |
As shown in the table above, all patients had proteinuria stabilization (lower variability vs. baseline) or improvement (reduction during or 2-months after treatment). This is consistent with clinical benefit and with the improvement in kidney morphology.
如上表所示，所有患者的蛋白尿均趋于稳定（与基线相比变异性较低）或改善（治疗期间或治疗后2个月内蛋白尿减少）。这与临床益处和肾脏形态的改善是一致的。
Renowned key opinion leaders have reviewed these data and overwhelmingly believe that they provide strong evidence of the potential of the disease modifying effect of ELX-02 and warrant advancement into a pivotal trial.
著名的主要意见领袖已经审查了这些数据，绝大多数人认为这些数据提供了有力的证据，证明了 ELX-02 可能具有改变疾病的作用，值得进入一项关键的试验。
About Nonsense Mutation Alport Syndrome
关于胡说八道突变 Alport 综合症
Nonsense Mutation Alport syndrome is a rare Type IV Collagenopathy characterized by mutations in the genes (COL4A3, COL4A4, and COL4A5) that result in a less than full length (truncated) Type 4 Collagen. This disorder mostly affects children with a median age at diagnosis of 9 to 20 years. It is characterized by rapid and progressive damage to the kidneys, ear and eyes, starting with worsening of kidney morphology to proteinuria and finally kidney failure, hearing loss and eye abnormalities. It is estimated that there are approximately 7,500 patients in the US and 20,000 patients in US, Europe, Japan and China with Nonsense Mutation Alport Syndrome. These patients have no approved treatment options.
胡说八道 Mutation Alport 综合征是一种罕见的 IV 型胶原病，其特征是基因（COL4A3、COL4A4 和 COL4A5）发生突变，导致小于全长（截断）的 4 型胶原蛋白。这种疾病主要影响诊断年龄中位数为9至20岁的儿童。其特征是肾脏、耳朵和眼睛受到快速而渐进的损害，首先是肾脏形态恶化为蛋白尿，最后是肾衰竭、听力损失和眼睛异常。据估计，美国大约有7,500名患者患有胡说八道突变Alport综合症，在美国、欧洲、日本和中国有2万名患者。这些患者没有经批准的治疗方案。
About Eloxx Pharmaceuticals
关于 Eloxx 制药
Eloxx Pharmaceuticals, Inc. is engaged in the science of ribosome modulation, leveraging its innovative TURBO-ZM chemistry technology platform in an effort to develop novel Ribosome Modulating Agents (RMAs) and its library of Eukaryotic Ribosome Selective Glycosides (ERSGs). Eloxx's lead investigational product candidate, ELX-02, is a small molecule drug candidate designed to restore production of full-length functional proteins. ELX-02 is in Phase 2 clinical development for the treatment of Alport syndrome in patients with nonsense mutations.
Eloxx Pharmicals, Inc. 从事核糖体调制科学，利用其创新的TURBO-ZM化学技术平台努力开发新的核糖体调节剂（RMA）及其真核生物核糖体选择性糖苷（ERSG）库。Eloxx的主要研究候选产品 ELX-02 是一种小分子候选药物，旨在恢复全长功能蛋白的产生。ELX-02 正处于治疗胡说八道突变患者的 Alport 综合征的 2 期临床开发阶段。